Body Fat Distribution Contributes to Defining the Relationship between
Insulin Resistance and Obesity in Human Diseases

María   M.   Adeva-Andany; Alberto      Domínguez-Montero; Lucía      Adeva-Contreras; Carlos      Fernández-Fernández; Natalia      Carneiro-Freire; Manuel      González-Lucán
doi:10.2174/1573399820666230816111624
Abstract

The risk for metabolic and cardiovascular complications of obesity is defined by body fat distribution rather than global adiposity. Unlike subcutaneous fat, visceral fat (including hepatic steatosis) reflects insulin resistance and predicts type 2 diabetes and cardiovascular disease. In humans, available evidence indicates that the ability to store triglycerides in the subcutaneous adipose tissue reflects enhanced insulin sensitivity. Prospective studies document an association between larger subcutaneous fat mass at baseline and reduced incidence of impaired glucose tolerance. Case-control studies reveal an association between genetic predisposition to insulin resistance and a lower amount of subcutaneous adipose tissue. Human peroxisome proliferator-activated receptorgamma (PPAR-γ) promotes subcutaneous adipocyte differentiation and subcutaneous fat deposition, improving insulin resistance and reducing visceral fat. Thiazolidinediones reproduce the effects of PPAR-γ activation and therefore increase the amount of subcutaneous fat while enhancing insulin sensitivity and reducing visceral fat. Partial or virtually complete lack of adipose tissue (lipodystrophy) is associated with insulin resistance and its clinical manifestations, including essential hypertension, hypertriglyceridemia, reduced HDL-c, type 2 diabetes, cardiovascular disease, and kidney disease. Patients with Prader Willi syndrome manifest severe subcutaneous obesity without insulin resistance. The impaired ability to accumulate fat in the subcutaneous adipose tissue may be due to deficient triglyceride synthesis, inadequate formation of lipid droplets, or defective adipocyte differentiation. Lean and obese humans develop insulin resistance when the capacity to store fat in the subcutaneous adipose tissue is exhausted and deposition of triglycerides is no longer attainable at that location. Existing adipocytes become large and reflect the presence of insulin resistance.
[1]
Akazawa S, Sun F, Ito M, Kawasaki E, Eguchi K. Efficacy of troglitazone on body fat distribution in type 2 diabetes. Diabetes Care  2000; 23(8): 1067-71.
 [http://dx.doi.org/10.2337/diacare.23.8.1067 ] [PMID: 10937499]

[2]
McLaughlin T, Lamendola C, Liu A, Abbasi F. Preferential fat deposition in subcutaneous versus visceral depots is associated with insulin sensitivity. J Clin Endocrinol Metab  2011; 96(11): E1756-60.
 [http://dx.doi.org/10.1210/jc.2011-0615 ] [PMID: 21865361]

[3]
Lotta LA, Gulati P, Day FR, et al. Integrative genomic analysis implicates limited peripheral adipose storage capacity in the pathogenesis of human insulin resistance. Nat Genet  2017; 49(1): 17-26.
 [http://dx.doi.org/10.1038/ng.3714 ] [PMID: 27841877]

[4]
Mtintsilana A, Micklesfield LK, Chorell E, Olsson T, Goedecke JH. Fat redistribution and accumulation of visceral adipose tissue predicts type 2 diabetes risk in middle-aged black South African women: A 13-year longitudinal study. Nutr Diabetes  2019; 9(1): 12.
 [http://dx.doi.org/10.1038/s41387-019-0079-8 ] [PMID: 30918247]

[5]
Barroso I, Gurnell M, Crowley VEF, et al. Dominant negative mutations in human PPARγ associated with severe insulin resistance, diabetes mellitus and hypertension. Nature  1999; 402(6764): 880-3.
 [http://dx.doi.org/10.1038/47254 ] [PMID: 10622252]

[6]
Agarwal AK, Garg A. A novel heterozygous mutation in peroxisome proliferator-activated receptor-gamma gene in a patient with familial partial lipodystrophy. J Clin Endocrinol Metab  2002; 87(1): 408-11.
 [http://dx.doi.org/10.1210/jcem.87.1.8290 ] [PMID: 11788685]

[7]
Hegele RA, Cao H, Frankowski C, Mathews ST, Leff T. PPARG F388L, a transactivation-deficient mutant, in familial partial lipodystrophy. Diabetes  2002; 51(12): 3586-90.
 [http://dx.doi.org/10.2337/diabetes.51.12.3586 ] [PMID: 12453919]

[8]
Savage DB, Tan GD, Acerini CL, et al. Human metabolic syndrome resulting from dominant-negative mutations in the nuclear receptor peroxisome proliferator-activated receptor-gamma. Diabetes  2003; 52(4): 910-7.
 [http://dx.doi.org/10.2337/diabetes.52.4.910 ] [PMID: 12663460]

[9]
Agostini M, Schoenmakers E, Mitchell C, et al. Non-DNA binding, dominant-negative, human PPARγ mutations cause lipodystrophic insulin resistance. Cell Metab  2006; 4(4): 303-11.
 [http://dx.doi.org/10.1016/j.cmet.2006.09.003 ] [PMID: 17011503]

[10]
Campeau PM, Astapova O, Martins R, et al. Clinical and molecular characterization of a severe form of partial lipodystrophy expanding the phenotype of PPARγ deficiency. J Lipid Res  2012; 53(9): 1968-78.
 [http://dx.doi.org/10.1194/jlr.P025437 ] [PMID: 22750678]

[11]
Mathieu-Costello O, Kong A, Ciaraldi TP, et al. Regulation of skeletal muscle morphology in type 2 diabetic subjects by troglitazone and metformin: Relationship to glucose disposal. Metabolism  2003; 52(5): 540-6.
 [http://dx.doi.org/10.1053/meta.2002.50108 ] [PMID: 12759881]

[12]
Rasouli N, Raue U, Miles LM, et al. Pioglitazone improves insulin sensitivity through reduction in muscle lipid and redistribution of lipid into adipose tissue. Am J Physiol Endocrinol Metab  2005; 288(5): E930-4.
 [http://dx.doi.org/10.1152/ajpendo.00522.2004 ] [PMID: 15632102]

[13]
Teranishi T, Ohara T, Maeda K, et al. Effects of pioglitazone and metformin on intracellular lipid content in liver and skeletal muscle of individuals with type 2 diabetes mellitus. Metabolism  2007; 56(10): 1418-24.
 [http://dx.doi.org/10.1016/j.metabol.2007.06.005 ] [PMID: 17884455]

[14]
Bajaj M, Baig R, Suraamornkul S, et al. Effects of pioglitazone on intramyocellular fat metabolism in patients with type 2 diabetes mellitus. J Clin Endocrinol Metab  2010; 95(4): 1916-23.
 [http://dx.doi.org/10.1210/jc.2009-0911 ] [PMID: 20157197]

[15]
Kodama S, Kasuga M, Seki A, et al. Congenital generalized lipodystrophy with insulin-resistant diabetes. Eur J Pediatr  1978; 127(2): 111-9.
 [http://dx.doi.org/10.1007/BF00445766 ] [PMID: 203464]

[16]
Tsukahara H, Kikuchi K, Kuzuya H, et al. Insulin resistance in a boy with congenital generalized lipodystrophy. Pediatr Res  1988; 24(6): 668-72.
 [http://dx.doi.org/10.1203/00006450-198812000-00003 ] [PMID: 3060827]

[17]
Søvik O, Vestergaard H, Trygstad O, Pedersen O. Studies of insulin resistance in congenital generalized lipodystrophy. Acta Paediatr  1996; 85(s413): 29-38.
 [http://dx.doi.org/10.1111/j.1651-2227.1996.tb14263.x ] [PMID: 8783770]

[18]
Garg A, Wilson R, Barnes R, et al. A gene for congenital generalized lipodystrophy maps to human chromosome 9q34. J Clin Endocrinol Metab  1999; 84(9): 3390-4.
 [http://dx.doi.org/10.1210/jcem.84.9.6103 ] [PMID: 10487716]

[19]
Magré J, Delépine M, Khallouf E, et al. Identification of the gene altered in Berardinelli–Seip congenital lipodystrophy on chromosome 11q13. Nat Genet  2001; 28(4): 365-70.
 [http://dx.doi.org/10.1038/ng585 ] [PMID: 11479539]

[20]
Agarwal AK, Arioglu E, de Almeida S, et al. AGPAT2 is mutated in congenital generalized lipodystrophy linked to chromosome 9q34. Nat Genet  2002; 31(1): 21-3.
 [http://dx.doi.org/10.1038/ng880 ] [PMID: 11967537]

[21]
Petersen KF, Oral EA, Dufour S, et al. Leptin reverses insulin resistance and hepatic steatosis in patients with severe lipodystrophy. J Clin Invest  2002; 109(10): 1345-50.
 [http://dx.doi.org/10.1172/JCI0215001 ] [PMID: 12021250]

[22]
Javor ED, Moran SA, Young JR, et al. Proteinuric nephropathy in acquired and congenital generalized lipodystrophy: Baseline characteristics and course during recombinant leptin therapy. J Clin Endocrinol Metab  2004; 89(7): 3199-207.
 [http://dx.doi.org/10.1210/jc.2003-032140 ] [PMID: 15240593]

[23]
Talebizadeh Z, Butler MG. Insulin resistance and obesity-related factors in Prader-Willi syndrome: Comparison with obese subjects. Clin Genet  2005; 67(3): 230-9.
 [http://dx.doi.org/10.1111/j.1399-0004.2004.00392.x ] [PMID: 15691361]

[24]
Kennedy L, Bittel DC, Kibiryeva N, Kalra SP, Torto R, Butler MG. Circulating adiponectin levels, body composition and obesity-related variables in Prader–Willi syndrome: Comparison with obese subjects. Int J Obes  2006; 30(2): 382-7.
 [http://dx.doi.org/10.1038/sj.ijo.0803115 ] [PMID: 16231029]

[25]
Krochik AG, Ozuna B, Torrado M, Chertkoff L, Mazza C. Characterization of alterations in carbohydrate metabolism in children with Prader-Willi syndrome. J Pediatr Endocrinol Metab  2006; 19(7): 911-8.
 [http://dx.doi.org/10.1515/JPEM.2006.19.7.911 ] [PMID: 16995571]

[26]
Neeland IJ, Turer AT, Ayers CR, et al. Dysfunctional adiposity and the risk of prediabetes and type 2 diabetes in obese adults. JAMA  2012; 308(11): 1150-9.
 [http://dx.doi.org/10.1001/2012.jama.11132 ] [PMID: 22990274]

[27]
Premanath M, Basavanagowdappa H, Mahesh M, Babu MS. Occurrence of diabetes mellitus in obese nondiabetic patients, with correlative analysis of visceral fat, fasting insulin, and insulin resistance: A 3-year follow-up study (mysore visceral adiposity in diabetes follow-up study). Indian J Endocrinol Metab  2017; 21(2): 308-15.
 [http://dx.doi.org/10.4103/ijem.IJEM_418_16 ] [PMID: 28459031]

[28]
Wu J, Gong L, Li Q, et al. A novel visceral adiposity index for prediction of Type 2 diabetes and pre-diabetes in chinese adults: A 5-year prospective study. Sci Rep  2017; 7(1): 13784.
 [http://dx.doi.org/10.1038/s41598-017-14251-w ] [PMID: 29062099]

[29]
Xia MF, Lin HD, Chen LY, et al. Association of visceral adiposity and its longitudinal increase with the risk of diabetes in Chinese adults: A prospective cohort study. Diabetes Metab Res Rev  2018; 34(7): e3048.
 [http://dx.doi.org/10.1002/dmrr.3048 ] [PMID: 30035847]

[30]
Larsson B, Svärdsudd K, Welin L, Wilhelmsen L, Björntorp P, Tibblin G. Abdominal adipose tissue distribution, obesity, and risk of cardiovascular disease and death: 13 year follow up of participants in the study of men born in 1913. BMJ  1984; 288(6428): 1401-4.
 [http://dx.doi.org/10.1136/bmj.288.6428.1401 ] [PMID: 6426576]

[31]
Lapidus L, Bengtsson C, Larsson B, Pennert K, Rybo E, Sjöström L. Distribution of adipose tissue and risk of cardiovascular disease and death: A 12 year follow up of participants in the population study of women in Gothenburg, Sweden. BMJ  1984; 289(6454): 1257-61.
 [http://dx.doi.org/10.1136/bmj.289.6454.1257 ] [PMID: 6437507]

[32]
Ohlson LO, Larsson B, Svärdsudd K, et al. The influence of body fat distribution on the incidence of diabetes mellitus. 13.5 years of follow-up of the participants in the study of men born in 1913. Diabetes  1985; 34(10): 1055-8.
 [http://dx.doi.org/10.2337/diab.34.10.1055 ] [PMID: 4043554]

[33]
Lundgren H, Bengtsson C, Blohme G, Lapidus L, Sjöström L. Adiposity and adipose tissue distribution in relation to incidence of diabetes in women: Results from a prospective population study in Gothenburg, Sweden. Int J Obes  1989; 13(4): 413-23.
 [PMID: 2793297]

[34]
Olivo RE, Davenport CA, Diamantidis CJ, et al. Obesity and synergistic risk factors for chronic kidney disease in African American adults: The Jackson Heart Study. Nephrol Dial Transplant  2018; 33(6): 992-1001.
 [http://dx.doi.org/10.1093/ndt/gfx230 ] [PMID: 28992354]

[35]
Weyer C, Foley JE, Bogardus C, Tataranni PA, Pratley RE. Enlarged subcutaneous abdominal adipocyte size, but not obesity itself, predicts Type II diabetes independent of insulin resistance. Diabetologia  2000; 43(12): 1498-506.
 [http://dx.doi.org/10.1007/s001250051560 ] [PMID: 11151758]

[36]
Jansson PA, Pellmé F, Hammarstedt A, et al. A novel cellular marker of insulin resistance and early atherosclerosis in humans is related to impaired fat cell differentiation and low adiponectin. FASEB J  2003; 17(11): 1434-40.
 [http://dx.doi.org/10.1096/fj.02-1132com ] [PMID: 12890697]

[37]
Hammarstedt A, Rotter Sopasakis V, Gogg S, Jansson PA, Smith U. Improved insulin sensitivity and adipose tissue dysregulation after short-term treatment with pioglitazone in non-diabetic, insulin-resistant subjects. Diabetologia  2005; 48(1): 96-104.
 [http://dx.doi.org/10.1007/s00125-004-1612-3 ] [PMID: 15624096]

[38]
Lundgren M, Svensson M, Lindmark S, Renström F, Ruge T, Eriksson JW. Fat cell enlargement is an independent marker of insulin resistance and ‘hyperleptinaemia’. Diabetologia  2007; 50(3): 625-33.
 [http://dx.doi.org/10.1007/s00125-006-0572-1 ] [PMID: 17216279]

[39]
Alligier M, Gabert L, Meugnier E, et al. Visceral fat accumulation during lipid overfeeding is related to subcutaneous adipose tissue characteristics in healthy men. J Clin Endocrinol Metab  2013; 98(2): 802-10.
 [http://dx.doi.org/10.1210/jc.2012-3289 ] [PMID: 23284008]

[40]
McLaughlin T, Lamendola C, Coghlan N, et al. Subcutaneous adipose cell size and distribution: Relationship to insulin resistance and body fat. Obesity (Silver Spring)  2014; 22(3): 673-80.
 [http://dx.doi.org/10.1002/oby.20209 ] [PMID: 23666871]

[41]
McLaughlin T, Craig C, Liu LF, et al. Adipose Cell Size and Regional Fat Deposition as Predictors of Metabolic Response to Overfeeding in Insulin-Resistant and Insulin-Sensitive Humans. Diabetes  2016; 65(5): 1245-54.
 [http://dx.doi.org/10.2337/db15-1213 ] [PMID: 26884438]

[42]
Lönn M, Mehlig K, Bengtsson C, Lissner L. Adipocyte size predicts incidence of type 2 diabetes in women. FASEB J  2010; 24(1): 326-31.
 [http://dx.doi.org/10.1096/fj.09-133058 ] [PMID: 19741173]

[43]
Chandalia M, Lin P, Seenivasan T, et al. Insulin resistance and body fat distribution in South Asian men compared to Caucasian men. PLoS One  2007; 2(8): e812.
 [http://dx.doi.org/10.1371/journal.pone.0000812 ] [PMID: 17726542]

[44]
Geberhiwot T, Baig S, Obringer C, et al. Relative adipose tissue failure in alström syndrome drives obesity-induced insulin resistance. diabetes  2021; 70(2): 364-76.
 [http://dx.doi.org/10.2337/db20-0647] [PMID: 32994277]

[45]
Vague J. The degree of masculine differentiation of obesities: A factor determining predisposition to diabetes, atherosclerosis, gout, and uric calculous disease. Am J Clin Nutr  1956; 4(1): 20-34.
 [http://dx.doi.org/10.1093/ajcn/4.1.20 ] [PMID: 13282851]

[46]
Kissebah AH, Vydelingum N, Murray R, et al. Relation of body fat distribution to metabolic complications of obesity. J Clin Endocrinol Metab  1982; 54(2): 254-60.
 [http://dx.doi.org/10.1210/jcem-54-2-254 ] [PMID: 7033275]

[47]
Hartz A, Rupley DC Jr, Kalkhoff RD, Rimm AA. Relationship of obesity to diabetes: Influence of obesity level and body fat distribution. Prev Med  1983; 12(2): 351-7.
 [http://dx.doi.org/10.1016/0091-7435(83)90244-X ] [PMID: 6878197]

[48]
Krotkiewski M, Björntorp P, Sjöström L, Smith U. Impact of obesity on metabolism in men and women. Importance of regional adipose tissue distribution. J Clin Invest  1983; 72(3): 1150-62.
 [http://dx.doi.org/10.1172/JCI111040 ] [PMID: 6350364]

[49]
Van Gaal LF, Vansant GA, De Leeuw IH. Upper body adiposity and the risk for atherosclerosis. J Am Coll Nutr  1989; 8(6): 504-14.
 [http://dx.doi.org/10.1080/07315724.1989.10720320 ] [PMID: 2695550]

[50]
Fujioka S, Matsuzawa Y, Tokunaga K, et al. Improvement of glucose and lipid metabolism associated with selective reduction of intra-abdominal visceral fat in premenopausal women with visceral fat obesity. Int J Obes  1991; 15(12): 853-9.
 [PMID: 1794928]

[51]
Matsuzawa Y, Shimomura I, Nakamura T, Keno Y, Kotani K, Tokunaga K. Pathophysiology and pathogenesis of visceral fat obesity. Obes Res  1995; 3(S2) (Suppl. 2): 187s-94s.
 [http://dx.doi.org/10.1002/j.1550-8528.1995.tb00462.x ] [PMID: 8581775]

[52]
Yamashita S, Nakamura T, Shimomura L, et al. Insulin Resistance and Body Fat Distribution: Contribution of visceral fat accumulation to the development of insulin resistance and atherosclerosis. Diabetes Care  1996; 19(3): 287-91.
 [http://dx.doi.org/10.2337/diacare.19.3.287 ] [PMID: 8742584]

[53]
Goldstone AP, Thomas EL, Brynes AE, et al. Visceral adipose tissue and metabolic complications of obesity are reduced in Prader-Willi syndrome female adults: Evidence for novel influences on body fat distribution. J Clin Endocrinol Metab  2001; 86(9): 4330-8.
 [http://dx.doi.org/10.1210/jcem.86.9.7814 ] [PMID: 11549670]

[54]
Wajchenberg BL, Giannella-Neto D, da Silva ME, Santos RF. Depot-specific hormonal characteristics of subcutaneous and visceral adipose tissue and their relation to the metabolic syndrome. Horm Metab Res  2002; 34(11/12): 616-21.
 [http://dx.doi.org/10.1055/s-2002-38256 ] [PMID: 12660870]

[55]
Nicklas BJ, Penninx BWJH, Ryan AS, Berman DM, Lynch NA, Dennis KE. Visceral adipose tissue cutoffs associated with metabolic risk factors for coronary heart disease in women. Diabetes Care  2003; 26(5): 1413-20.
 [http://dx.doi.org/10.2337/diacare.26.5.1413 ] [PMID: 12716798]

[56]
Gastaldelli A, Cusi K, Pettiti M, et al. Relationship between hepatic/visceral fat and hepatic insulin resistance in nondiabetic and type 2 diabetic subjects. Gastroenterology  2007; 133(2): 496-506.
 [http://dx.doi.org/10.1053/j.gastro.2007.04.068 ] [PMID: 17681171]

[57]
Umegaki H, Haimoto H, Ishikawa J, Kario K. Visceral fat contribution of insulin resistance in elderly people. J Am Geriatr Soc  2008; 56(7): 1373-5.
 [http://dx.doi.org/10.1111/j.1532-5415.2008.01730.x ] [PMID: 18774980]

[58]
Usui C, Asaka M, Kawano H, et al. Visceral fat is a strong predictor of insulin resistance regardless of cardiorespiratory fitness in non-diabetic people. J Nutr Sci Vitaminol (Tokyo)  2010; 56(2): 109-16.
 [http://dx.doi.org/10.3177/jnsv.56.109 ] [PMID: 20495292]

[59]
Philipsen A, Jørgensen ME, Vistisen D, et al. Associations between ultrasound measures of abdominal fat distribution and indices of glucose metabolism in a population at high risk of type 2 diabetes: The ADDITION-PRO study. PLoS One  2015; 10(4): e0123062.
 [http://dx.doi.org/10.1371/journal.pone.0123062 ] [PMID: 25849815]

[60]
Jung SH, Ha KH, Kim DJ. Visceral Fat Mass Has Stronger Associations with Diabetes and Prediabetes than Other Anthropometric Obesity Indicators among Korean Adults. Yonsei Med J  2016; 57(3): 674-80.
 [http://dx.doi.org/10.3349/ymj.2016.57.3.674 ] [PMID: 26996568]

[61]
Lee JJ, Pedley A, Hoffmann U, Massaro JM, Levy D, Long MT. Visceral and intrahepatic fat are associated with cardiometabolic risk factors above other ectopic fat depots: The Framingham Heart Study. Am J Med  2018; 131(6): 684-692.e12.
 [http://dx.doi.org/10.1016/j.amjmed.2018.02.002 ] [PMID: 29518370]

[62]
Zhang M, Hu T, Zhang S, Zhou L. Associations of different adipose tissue depots with insulin resistance: A Systematic Review and Meta-analysis of Observational Studies. Sci Rep  2015; 5(1): 18495.
 [http://dx.doi.org/10.1038/srep18495 ] [PMID: 26686961]

[63]
Gaal LV, Rillaerts E, Creten W, Leeuw ID. Relationship of body fat distribution pattern to atherogenic risk factors in NIDDM. Preliminary results. Diabetes Care  1988; 11(2): 103-6.
 [http://dx.doi.org/10.2337/diacare.11.2.103 ] [PMID: 3383730]

[64]
Abate N, Garg A, Peshock RM, Stray-Gundersen J, Adams-Huet B, Grundy SM. Relationship of generalized and regional adiposity to insulin sensitivity in men with NIDDM. Diabetes  1996; 45(12): 1684-93.
 [http://dx.doi.org/10.2337/diab.45.12.1684 ] [PMID: 8922352]

[65]
Banerji MA, Buckley MC, Chaiken RL, Gordon D, Lebovitz HE, Kral JG. Liver fat, serum triglycerides and visceral adipose tissue in insulin-sensitive and insulin-resistant black men with NIDDM. Int J Obes Relat Metab Disord  1995; 19(12): 846-50.
 [PMID: 8963350]

[66]
Ryysy L, Häkkinen AM, Goto T, et al. Hepatic fat content and insulin action on free fatty acids and glucose metabolism rather than insulin absorption are associated with insulin requirements during insulin therapy in type 2 diabetic patients. Diabetes  2000; 49(5): 749-58.
 [http://dx.doi.org/10.2337/diabetes.49.5.749 ] [PMID: 10905483]

[67]
Kotronen A, Juurinen L, Tiikkainen M, Vehkavaara S, Yki-Järvinen H. Increased liver fat, impaired insulin clearance, and hepatic and adipose tissue insulin resistance in type 2 diabetes. Gastroenterology  2008; 135(1): 122-30.
 [http://dx.doi.org/10.1053/j.gastro.2008.03.021 ] [PMID: 18474251]

[68]
Goto T, Onuma T, Takebe K, Kral JG. The influence of fatty liver on insulin clearance and insulin resistance in non-diabetic Japanese subjects. Int J Obes Relat Metab Disord  1995; 19(12): 841-5.
 [PMID: 8963349]

[69]
Sookoian S, Pirola CJ. Systematic review with meta-analysis: Risk factors for non-alcoholic fatty liver disease suggest a shared altered metabolic and cardiovascular profile between lean and obese patients. Aliment Pharmacol Ther  2017; 46(2): 85-95.
 [http://dx.doi.org/10.1111/apt.14112 ] [PMID: 28464369]

[70]
Ballestri S, Zona S, Targher G, et al. Nonalcoholic fatty liver disease is associated with an almost twofold increased risk of incident type 2 diabetes and metabolic syndrome. Evidence from a systematic review and meta-analysis. J Gastroenterol Hepatol  2016; 31(5): 936-44.
 [http://dx.doi.org/10.1111/jgh.13264 ] [PMID: 26667191]

[71]
Alexander M, Loomis AK, van der Lei J, et al. Non-alcoholic fatty liver disease and risk of incident acute myocardial infarction and stroke: Findings from matched cohort study of 18 million European adults. BMJ  2019; 367: l5367.
 [http://dx.doi.org/10.1136/bmj.l5367 ] [PMID: 31594780]

[72]
Ma W, Wu W, Wen W, et al. Association of NAFLD with cardiovascular disease and all-cause mortality: A large-scale prospective cohort study based on UK Biobank. Ther Adv Chronic Dis  2022; 13
 [http://dx.doi.org/10.1177/20406223221122478 ] [PMID: 36159632]

[73]
Heni M, Machann J, Staiger H, et al. Pancreatic fat is negatively associated with insulin secretion in individuals with impaired fasting glucose and/or impaired glucose tolerance: A nuclear magnetic resonance study. Diabetes Metab Res Rev  2010; 26(3): 200-5.
 [http://dx.doi.org/10.1002/dmrr.1073 ] [PMID: 20225188]

[74]
Lu T, Wang Y, Dou T, Xue B, Tan Y, Yang J. Pancreatic fat content is associated with β-cell function and insulin resistance in Chinese type 2 diabetes subjects. Endocr J  2019; 66(3): 265-70.
 [http://dx.doi.org/10.1507/endocrj.EJ18-0436 ] [PMID: 30700664]

[75]
Li YX, Sang YQ, Sun Y, et al. Pancreatic fat is not significantly correlated with β-cell dysfunction in patients with new-onset Type 2 diabetes mellitus using quantitative computed tomography. Int J Med Sci  2020; 17(12): 1673-82.
 [http://dx.doi.org/10.7150/ijms.46395 ] [PMID: 32714070]

[76]
Staaf J, Labmayr V, Paulmichl K, et al. Pancreatic fat Is associated with metabolic syndrome and visceral fat but Not beta-cell function or body mass index in pediatric obesity. Pancreas  2017; 46(3): 358-65.
 [http://dx.doi.org/10.1097/MPA.0000000000000771 ] [PMID: 27941426]

[77]
Miljkovic I, Kuipers AL, Cvejkus R, et al. Myosteatosis increases with aging and is associated with incident diabetes in African ancestry men. Obesity (Silver Spring)  2016; 24(2): 476-82.
 [http://dx.doi.org/10.1002/oby.21328 ] [PMID: 26694517]

[78]
Stellingwerff T, Boon H, Jonkers RAM, et al. Significant intramyocellular lipid use during prolonged cycling in endurance-trained males as assessed by three different methodologies. Am J Physiol Endocrinol Metab  2007; 292(6): E1715-23.
 [http://dx.doi.org/10.1152/ajpendo.00678.2006 ] [PMID: 17299080]

[79]
Smith SR, Lovejoy JC, Greenway F, et al. Contributions of total body fat, abdominal subcutaneous adipose tissue compartments, and visceral adipose tissue to the metabolic complications of obesity. Metabolism  2001; 50(4): 425-35.
 [http://dx.doi.org/10.1053/meta.2001.21693 ] [PMID: 11288037]

[80]
Kelley DE, Thaete FL, Troost F, Huwe T, Goodpaster BH. Subdivisions of subcutaneous abdominal adipose tissue and insulin resistance. Am J Physiol Endocrinol Metab  2000; 278(5): E941-8.
 [http://dx.doi.org/10.1152/ajpendo.2000.278.5.E941 ] [PMID: 10780952]

[81]
Yang M, Lin J, Ma X, et al. Truncal and leg fat associations with metabolic risk factors among Chinese adults. Asia Pac J Clin Nutr  2016; 25(4): 798-809.
 [http://dx.doi.org/10.6133/apjcn.092015.35 ] [PMID: 27702723]

[82]
Misra A, Vikram NK, Arya S, et al. High prevalence of insulin resistance in postpubertal Asian Indian children is associated with adverse truncal body fat patterning, abdominal adiposity and excess body fat. Int J Obes  2004; 28(10): 1217-26.
 [http://dx.doi.org/10.1038/sj.ijo.0802704 ] [PMID: 15314636]

[83]
Albu JB, Kovera AJ, Johnson JA. Fat distribution and health in obesity. Ann N Y Acad Sci  2000; 904(1): 491-501.
 [http://dx.doi.org/10.1111/j.1749-6632.2000.tb06505.x ] [PMID: 10865794]

[84]
Marcus MA, Murphy L, Pi-Sunyer FX, Albu JB. Insulin sensitivity and serum triglyceride level in obese white and black women: Relationship to visceral and truncal subcutaneous fat. Metabolism  1999; 48(2): 194-9.
 [http://dx.doi.org/10.1016/S0026-0495(99)90033-1 ] [PMID: 10024081]

[85]
Wu C-H, Heshka S, Wang J, et al. Truncal fat in relation to total body fat: Influences of age, sex, ethnicity and fatness. Int J Obes  2007; 31(9): 1384-91.
 [http://dx.doi.org/10.1038/sj.ijo.0803624 ] [PMID: 17452992]

[86]
Numao S, Katayama Y, Nakata Y, Matsuo T, Nakagaichi M, Tanaka K. Association of abdominal fat with metabolic syndrome components in overweight women: Effect of menopausal status. J Physiol Anthropol  2020; 39(1): 12.
 [http://dx.doi.org/10.1186/s40101-020-00222-0 ] [PMID: 32307016]

[87]
Lambe KG, Tugwood JD. A human peroxisome-proliferator-activated receptor-gamma is activated by inducers of adipogenesis, including thiazolidinedione drugs. Eur J Biochem  1996; 239(1): 1-7.
 [http://dx.doi.org/10.1111/j.1432-1033.1996.0001u.x ] [PMID: 8706692]

[88]
Fajas L, Auboeuf D, Raspé E, et al. The organization, promoter analysis, and expression of the human PPARgamma gene. J Biol Chem  1997; 272(30): 18779-89.
 [http://dx.doi.org/10.1074/jbc.272.30.18779 ] [PMID: 9228052]

[89]
Vidal-Puig AJ, Considine RV, Jimenez-Liñan M, et al. Peroxisome proliferator-activated receptor gene expression in human tissues. Effects of obesity, weight loss, and regulation by insulin and glucocorticoids. J Clin Invest  1997; 99(10): 2416-22.
 [http://dx.doi.org/10.1172/JCI119424 ] [PMID: 9153284]

[90]
Yanase T, Yashiro T, Takitani K, et al. Differential expression of PPAR gamma1 and gamma2 isoforms in human adipose tissue. Biochem Biophys Res Commun  1997; 233(2): 320-4.
 [http://dx.doi.org/10.1006/bbrc.1997.6446 ] [PMID: 9144532]

[91]
Adams M, Montague CT, Prins JB, et al. Activators of peroxisome proliferator-activated receptor gamma have depot-specific effects on human preadipocyte differentiation. J Clin Invest  1997; 100(12): 3149-53.
 [http://dx.doi.org/10.1172/JCI119870 ] [PMID: 9399962]

[92]
Fajas L, Fruchart JC, Auwerx J. PPARγ3 mRNA: A distinct PPARγ mRNA subtype transcribed from an independent promoter. FEBS Lett  1998; 438(1-2): 55-60.
 [http://dx.doi.org/10.1016/S0014-5793(98)01273-3 ] [PMID: 9821958]

[93]
Auboeuf D, Rieusset J, Fajas L, et al. Tissue distribution and quantification of the expression of mRNAs of peroxisome proliferator-activated receptors and liver X receptor-alpha in humans: No alteration in adipose tissue of obese and NIDDM patients. Diabetes  1997; 46(8): 1319-27.
 [http://dx.doi.org/10.2337/diab.46.8.1319 ] [PMID: 9231657]

[94]
Lefebvre AM, Laville M, Vega N, et al. Depot-specific differences in adipose tissue gene expression in lean and obese subjects. Diabetes  1998; 47(1): 98-103.
 [http://dx.doi.org/10.2337/diab.47.1.98 ] [PMID: 9421381]

[95]
Dubois M, Pattou F, Kerr-Conte J, et al. Expression of peroxisome proliferator-activated receptor γ (PPARγ) in normal human pancreatic islet cells. Diabetologia  2000; 43(9): 1165-9.
 [http://dx.doi.org/10.1007/s001250051508 ] [PMID: 11043863]

[96]
McLaughlin T, Sherman A, Tsao P, et al. Enhanced proportion of small adipose cells in insulin-resistant vs. insulin-sensitive obese individuals implicates impaired adipogenesis. Diabetologia  2007; 50(8): 1707-15.
 [http://dx.doi.org/10.1007/s00125-007-0708-y ] [PMID: 17549449]

[97]
Dyment DA, Gibson WT, Huang L, Bassyouni H, Hegele RA, Innes AM. Biallelic mutations at PPARG cause a congenital, generalized lipodystrophy similar to the Berardinelli–Seip syndrome. Eur J Med Genet  2014; 57(9): 524-6.
 [http://dx.doi.org/10.1016/j.ejmg.2014.06.006 ] [PMID: 24980513]

[98]
Francis GA, Li G, Casey R, et al. Peroxisomal proliferator activated receptor-γ deficiency in a Canadian kindred with familial partial lipodystrophy type 3 (FPLD3). BMC Med Genet  2006; 7(1): 3.
 [http://dx.doi.org/10.1186/1471-2350-7-3 ] [PMID: 16412238]

[99]
Rutkowska L, Salachna D, Lewandowski K. Lewiński A, Gach A. Familial partial lipodystrophy-literature review and report of a novel variant in PPARG expanding the spectrum of disease-causing alterations in FPLD3. Diagnostics  2022; 12(5): 1122.
 [http://dx.doi.org/10.3390/diagnostics12051122]

[100]
Lambadiari V, Kountouri A, Maratou E, Liatis S, Dimitriadis GD, Karpe F. Case report: metreleptin treatment in a patient with a novel mutation for familial partial lipodystrophy Type 3, presenting with uncontrolled diabetes and insulin resistance. front endocrinol (lausanne)  2021; 12: 684182.
 [http://dx.doi.org/10.3389/fendo.2021.684182] [PMID: 34168618]

[101]
Majithia AR, Flannick J, Shahinian P, et al. Rare variants in PPARG with decreased activity in adipocyte differentiation are associated with increased risk of type 2 diabetes. Proc Natl Acad Sci USA  2014; 111(36): 13127-32.
 [http://dx.doi.org/10.1073/pnas.1410428111 ] [PMID: 25157153]

[102]
Sarhangi N, Sharifi F, Hashemian L, et al. PPARG (Pro12Ala) genetic variant and risk of T2DM: A systematic review and meta-analysis. Sci Rep  2020; 10(1): 12764.
 [http://dx.doi.org/10.1038/s41598-020-69363-7 ] [PMID: 32728045]

[103]
Kelly IE, Han TS, Walsh K, Lean ME. Effects of a thiazolidinedione compound on body fat and fat distribution of patients with type 2 diabetes. Diabetes Care  1999; 22(2): 288-93.
 [http://dx.doi.org/10.2337/diacare.22.2.288 ] [PMID: 10333947]

[104]
Mori Y, Murakawa Y, Okada K, et al. Effect of troglitazone on body fat distribution in type 2 diabetic patients. Diabetes Care  1999; 22(6): 908-12.
 [http://dx.doi.org/10.2337/diacare.22.6.908 ] [PMID: 10372240]

[105]
Kawai T, Takei I, Oguma Y, et al. Effects of troglitazone on fat distribution in the treatment of male type 2 diabetes. Metabolism  1999; 48(9): 1102-7.
 [http://dx.doi.org/10.1016/S0026-0495(99)90122-1 ] [PMID: 10484048]

[106]
Arioglu E, Duncan-Morin J, Sebring N, et al. Efficacy and safety of troglitazone in the treatment of lipodystrophy syndromes. Ann Intern Med  2000; 133(4): 263-74.
 [http://dx.doi.org/10.7326/0003-4819-133-4-200008150-00009 ] [PMID: 10929166]

[107]
Katoh S, Hata S, Matsushima M, et al. Troglitazone prevents the rise in visceral adiposity and improves fatty liver associated with sulfonylurea therapy—A randomized controlled trial. Metabolism  2001; 50(4): 414-7.
 [http://dx.doi.org/10.1053/meta.2001.21691 ] [PMID: 11288035]

[108]
Ciaraldi TP, Kong APS, Chu NV, et al. Regulation of glucose transport and insulin signaling by troglitazone or metformin in adipose tissue of type 2 diabetic subjects. Diabetes  2002; 51(1): 30-6.
 [http://dx.doi.org/10.2337/diabetes.51.1.30 ] [PMID: 11756319]

[109]
Miyazaki Y, Mahankali A, Matsuda M, et al. Effect of pioglitazone on abdominal fat distribution and insulin sensitivity in type 2 diabetic patients. J Clin Endocrinol Metab  2002; 87(6): 2784-91.
 [http://dx.doi.org/10.1210/jcem.87.6.8567 ] [PMID: 12050251]

[110]
Bajaj M, Suraamornkul S, Pratipanawatr T, et al. Pioglitazone reduces hepatic fat content and augments splanchnic glucose uptake in patients with type 2 diabetes. Diabetes  2003; 52(6): 1364-70.
 [http://dx.doi.org/10.2337/diabetes.52.6.1364 ] [PMID: 12765945]

[111]
Schernthaner G, Matthews DR, Charbonnel B, Hanefeld M, Brunetti P. Efficacy and safety of pioglitazone versus metformin in patients with type 2 diabetes mellitus: A double-blind, randomized trial. J Clin Endocrinol Metab  2004; 89(12): 6068-76.
 [http://dx.doi.org/10.1210/jc.2003-030861 ] [PMID: 15579760]

[112]
Smith SR, de Jonge L, Volaufova J, Li Y, Xie H, Bray GA. Effect of pioglitazone on body composition and energy expenditure: A randomized controlled trial. Metabolism  2005; 54(1): 24-32.
 [http://dx.doi.org/10.1016/j.metabol.2004.07.008 ] [PMID: 15562376]

[113]
Kodama N, Tahara N, Tahara A, et al. Effects of pioglitazone on visceral fat metabolic activity in impaired glucose tolerance or type 2 diabetes mellitus. J Clin Endocrinol Metab  2013; 98(11): 4438-45.
 [http://dx.doi.org/10.1210/jc.2013-2920 ] [PMID: 24030946]

[114]
Filipova E, Uzunova K, Kalinov K, Vekov T. Effects of pioglitazone therapy on blood parameters, weight and BMI: A meta-analysis. Diabetol Metab Syndr  2017; 9(1): 90.
 [http://dx.doi.org/10.1186/s13098-017-0290-5 ] [PMID: 29163673]

[115]
Nakamura T, Funahashi T, Yamashita S, et al. Thiazolidinedione derivative improves fat distribution and multiple risk factors in subjects with visceral fat accumulation—double-blind placebo-controlled trial. Diabetes Res Clin Pract  2001; 54(3): 181-90.
 [http://dx.doi.org/10.1016/S0168-8227(01)00319-9 ] [PMID: 11689273]

[116]
Bray GA, Smith SR, Banerji MA, et al. Effect of pioglitazone on body composition and bone density in subjects with prediabetes in the ACT NOW trial. Diabetes Obes Metab  2013; 15(10): 931-7.
 [http://dx.doi.org/10.1111/dom.12099 ] [PMID: 23551856]

[117]
Nolan JJ, Ludvik B, Beerdsen P, Joyce M, Olefsky J. Improvement in glucose tolerance and insulin resistance in obese subjects treated with troglitazone. N Engl J Med  1994; 331(18): 1188-93.
 [http://dx.doi.org/10.1056/NEJM199411033311803 ] [PMID: 7935656]

[118]
Suter SL, Nolan JJ, Wallace P, Gumbiner B, Olefsky JM. Metabolic effects of new oral hypoglycemic agent CS-045 in NIDDM subjects. Diabetes Care  1992; 15(2): 193-203.
 [http://dx.doi.org/10.2337/diacare.15.2.193 ] [PMID: 1547676]

[119]
Inzucchi SE, Maggs DG, Spollett GR, et al. Efficacy and metabolic effects of metformin and troglitazone in type II diabetes mellitus. N Engl J Med  1998; 338(13): 867-73.
 [http://dx.doi.org/10.1056/NEJM199803263381303 ] [PMID: 9516221]

[120]
Maggs DG, Buchanan TA, Burant CF, et al. Metabolic effects of troglitazone monotherapy in type 2 diabetes mellitus. A randomized, double-blind, placebo-controlled trial. Ann Intern Med  1998; 128(3): 176-85.
 [http://dx.doi.org/10.7326/0003-4819-128-3-199802010-00002 ] [PMID: 9454525]

[121]
Koivisto VA, Pelkonen R, Cantell K. Effect of interferon on glucose tolerance and insulin sensitivity. Diabetes  1989; 38(5): 641-7.
 [http://dx.doi.org/10.2337/diab.38.5.641 ] [PMID: 2653935]

[122]
Shiba T, Higashi N, Nishimura Y. Hyperglycaemia due to insulin resistance caused by interferon-γ. Diabet Med  1998; 15(5): 435-6.
 [http://dx.doi.org/10.1002/(SICI)1096-9136(199805)15:5<435:AID-DIA566>3.0.CO;2-N ] [PMID: 9609368]

[123]
Ghosh AR, Bhattacharya R, Bhattacharya S, et al. Adipose recruitment and activation of plasmacytoid dendritic cells fuel metaflammation. Diabetes  2016; 65(11): 3440-52.
 [http://dx.doi.org/10.2337/db16-0331 ] [PMID: 27561727]

[124]
Faber DR, van der Graaf Y, Westerink J, Kanhai DA, Monajemi H, Visseren FLJ. Hepatocyte growth factor and interferon-γ inducible protein-10 are related to visceral adiposity. Eur J Clin Invest  2013; 43(4): 369-78.
 [http://dx.doi.org/10.1111/eci.12054 ] [PMID: 23398210]

[125]
O’Rourke RW, Metcalf MD, White AE, et al. Depot-specific differences in inflammatory mediators and a role for NK cells and IFN-γ in inflammation in human adipose tissue. Int J Obes  2009; 33(9): 978-90.
 [http://dx.doi.org/10.1038/ijo.2009.133 ] [PMID: 19564875]

[126]
Bradley D, Smith AJ, Blaszczak A, et al. Interferon gamma mediates the reduction of adipose tissue regulatory T cells in human obesity. Nat Commun  2022; 13(1): 5606.
 [http://dx.doi.org/10.1038/s41467-022-33067-5 ] [PMID: 36153324]

[127]
McGillicuddy FC, Chiquoine EH, Hinkle CC, et al. Interferon gamma attenuates insulin signaling, lipid storage, and differentiation in human adipocytes via activation of the JAK/STAT pathway. J Biol Chem  2009; 284(46): 31936-44.
 [http://dx.doi.org/10.1074/jbc.M109.061655 ] [PMID: 19776010]

[128]
Wentworth JM, Zhang J-G, Bandala-Sanchez E, et al. Interferon-gamma released from omental adipose tissue of insulin-resistant humans alters adipocyte phenotype and impairs response to insulin and adiponectin release. Int J Obes  2017; 41(12): 1782-9.
 [http://dx.doi.org/10.1038/ijo.2017.180 ] [PMID: 28769120]

[129]
Vandorpe DH, Heneghan JF, Waitzman JS, et al. Apolipoprotein L1 (APOL1) cation current in HEK-293 cells and in human podocytes. Pflugers Arch  2023; 475(3): 323-41.
 [http://dx.doi.org/10.1007/s00424-022-02767-8 ] [PMID: 36449077]

[130]
Davis SE, Khatua AK, Popik W. Nucleosomal dsDNA stimulates APOL1 expression in human cultured podocytes by activating the cGAS/IFI16-STING signaling pathway. Sci Rep  2019; 9(1): 15485.
 [http://dx.doi.org/10.1038/s41598-019-51998-w ] [PMID: 31664093]

[131]
Kumar V, Vashistha H, Lan X, et al. Role of Apolipoprotein L1 in Human Parietal Epithelial Cell Transition. Am J Pathol  2018; 188(11): 2508-28.
 [http://dx.doi.org/10.1016/j.ajpath.2018.07.025 ] [PMID: 30201495]

[132]
Nichols B, Jog P, Lee JH, et al. Innate immunity pathways regulate the nephropathy gene Apolipoprotein L1. Kidney Int  2015; 87(2): 332-42.
 [http://dx.doi.org/10.1038/ki.2014.270 ] [PMID: 25100047]

[133]
Taylor HE, Khatua AK, Popik W. The innate immune factor apolipoprotein L1 restricts HIV-1 infection. J Virol  2014; 88(1): 592-603.
 [http://dx.doi.org/10.1128/JVI.02828-13 ] [PMID: 24173214]

[134]
Zhaorigetu S, Wan G, Kaini R, Wan G, Jiang Z, Hu CA. ApoL1, a BH3-only lipid-binding protein, induces autophagic cell death. Autophagy  2008; 4(8): 1079-82.
 [http://dx.doi.org/10.4161/auto.7066 ] [PMID: 18927493]

[135]
Genovese G, Friedman DJ, Ross MD, et al. Association of trypanolytic ApoL1 variants with kidney disease in African Americans. Science  2010; 329(5993): 841-5.
 [http://dx.doi.org/10.1126/science.1193032 ] [PMID: 20647424]

[136]
Tzur S, Rosset S, Shemer R, et al. Missense mutations in the APOL1 gene are highly associated with end stage kidney disease risk previously attributed to the MYH9 gene. Hum Genet  2010; 128(3): 345-50.
 [http://dx.doi.org/10.1007/s00439-010-0861-0 ] [PMID: 20635188]

[137]
Chun J, Zhang JY, Wilkins MS, et al. Recruitment of APOL1 kidney disease risk variants to lipid droplets attenuates cell toxicity. Proc Natl Acad Sci USA  2019; 116(9): 3712-21.
 [http://dx.doi.org/10.1073/pnas.1820414116 ] [PMID: 30733285]

[138]
Chun J, Riella CV, Chung H, et al. DGAT2 inhibition potentiates lipid droplet formation to reduce cytotoxicity in APOL1 kidney risk variants. J Am Soc Nephrol  2022; 33(5): 889-907.
 [http://dx.doi.org/10.1681/ASN.2021050723 ] [PMID: 35232775]

[139]
Nadkarni GN, Galarneau G, Ellis SB, et al. Apolipoprotein L1 variants and blood pressure traits in african americans. J Am Coll Cardiol  2017; 69(12): 1564-74.
 [http://dx.doi.org/10.1016/j.jacc.2017.01.040 ] [PMID: 28335839]

[140]
Nadkarni GN, Fei K, Galarneau G, et al. APOL1 renal risk variants are associated with obesity and body composition in African ancestry adults. Medicine (Baltimore)  2021; 100(45): e27785.
 [http://dx.doi.org/10.1097/MD.0000000000027785 ] [PMID: 34766590]

[141]
Friedman DJ, Kozlitina J, Genovese G, Jog P, Pollak MR. Population-based risk assessment of APOL1 on renal disease. J Am Soc Nephrol  2011; 22(11): 2098-105.
 [http://dx.doi.org/10.1681/ASN.2011050519 ] [PMID: 21997396]

[142]
Parsa A, Kao WHL, Xie D, et al. APOL1 risk variants, race, and progression of chronic kidney disease. N Engl J Med  2013; 369(23): 2183-96.
 [http://dx.doi.org/10.1056/NEJMoa1310345 ] [PMID: 24206458]

[143]
Freedman BI, Rocco MV, Bates JT, et al. APOL1 renal-risk variants do not associate with incident cardiovascular disease or mortality in the Systolic Blood Pressure Intervention Trial. Kidney Int Rep  2017; 2(4): 713-20.
 [http://dx.doi.org/10.1016/j.ekir.2017.03.008 ] [PMID: 28758155]

[144]
Chen TK, Katz R, Estrella MM, et al. Association Between APOL1 Genotypes and Risk of Cardiovascular Disease in MESA (Multi‐Ethnic Study of Atherosclerosis). J Am Heart Assoc  2017; 6(12): e007199.
 [http://dx.doi.org/10.1161/JAHA.117.007199 ] [PMID: 29269352]

[145]
Bick AG, Akwo E, Robinson-Cohen C, et al. Association of APOL1 risk alleles with cardiovascular disease in blacks in the million veteran program. Circulation  2019; 140(12): 1031-40.
 [http://dx.doi.org/10.1161/CIRCULATIONAHA.118.036589 ] [PMID: 31337231]

[146]
Hoy WE, Hughson MD, Kopp JB, Mott SA, Bertram JF, Winkler CA. APOL1 Risk Alleles Are Associated with Exaggerated Age-Related Changes in Glomerular Number and Volume in African-American Adults. J Am Soc Nephrol  2015; 26(12): 3179-89.
 [http://dx.doi.org/10.1681/ASN.2014080768 ] [PMID: 26038529]

[147]
Hughson MD, Hoy WE, Mott SA, et al. APOL1 risk alleles are associated with more severe arteriosclerosis in renal resistance vessels with aging and hypertension. Kidney Int Rep  2016; 1(1): 10-23.
 [http://dx.doi.org/10.1016/j.ekir.2016.03.002 ] [PMID: 27610422]

[148]
Valdez Imbert R, Hti Lar Seng NS, Stokes MB, Jim B. Obesity-related glomerulopathy in the presence of APOL1 risk alleles. BMJ Case Rep  2022; 15(8): e249624.
 [http://dx.doi.org/10.1136/bcr-2022-249624 ] [PMID: 35985743]

[149]
Eiholzer U, Blum WF, Molinari L. Body fat determined by skinfold measurements is elevated despite underweight in infants with Prader-Labhart-Willi syndrome. J Pediatr  1999; 134(2): 222-5.
 [http://dx.doi.org/10.1016/S0022-3476(99)70419-1 ] [PMID: 9931533]

[150]
Bekx MT, Carrel AL, Shriver TC, Li Z, Allen DB. Decreased energy expenditure is caused by abnormal body composition in infants with Prader-Willi Syndrome. J Pediatr  2003; 143(3): 372-6.
 [http://dx.doi.org/10.1067/S0022-3476(03)00386-X ] [PMID: 14517523]

[151]
Olarescu NC, Jørgensen AP, Godang K, Jurik AG, Frøslie KF, Bollerslev J. Dual-energy X-ray absorptiometry is a valid method to estimate visceral adipose tissue in adult patients with Prader-Willi syndrome during treatment with growth hormone. J Clin Endocrinol Metab  2014; 99(9): E1727-31.
 [http://dx.doi.org/10.1210/jc.2014-2059 ] [PMID: 24955611]

[152]
van Nieuwpoort IC, Twisk JWR, Curfs LMG, Lips P, Drent ML. Body composition, adipokines, bone mineral density and bone remodeling markers in relation to IGF-1 levels in adults with Prader-Willi syndrome. Int J Pediatr Endocrinol  2018; 2018(1): 1.
 [http://dx.doi.org/10.1186/s13633-018-0055-4 ] [PMID: 29371863]

[153]
Mai S, Fintini D, Mele C, et al. Circulating irisin in children and Adolescents With Prader-willi syndrome: relation with glucose metabolism. front endocrinol (lausanne)  2022; 13: 918467.
 [http://dx.doi.org/10.3389/fendo.2022.918467] [PMID: 35774143]

[154]
Brambilla P, Bosio L, Manzoni P, Pietrobelli A, Beccaria L, Chiumello G. Peculiar body composition in patients with Prader-Labhart-Willi syndrome. Am J Clin Nutr  1997; 65(5): 1369-74.
 [http://dx.doi.org/10.1093/ajcn/65.5.1369 ] [PMID: 9129464]

[155]
Theodoro MF, Talebizadeh Z, Butler MG. Body composition and fatness patterns in Prader-Willi syndrome: Comparison with simple obesity. Obesity (Silver Spring)  2006; 14(10): 1685-90.
 [http://dx.doi.org/10.1038/oby.2006.193 ] [PMID: 17062796]

[156]
Sode-Carlsen R, Farholt S, Rabben KF, et al. Body composition, endocrine and metabolic profiles in adults with Prader-Willi syndrome. Growth Horm IGF Res  2010; 20(3): 179-84.
 [http://dx.doi.org/10.1016/j.ghir.2009.12.004 ] [PMID: 20199883]

[157]
Tanaka Y, Abe Y, Oto Y, et al. Characterization of fat distribution in Prader-Willi syndrome: Relationships with adipocytokines and influence of growth hormone treatment. Am J Med Genet A  2013; 161(1): 27-33.
 [http://dx.doi.org/10.1002/ajmg.a.35653 ] [PMID: 23239671]

[158]
l’Allemand D, Eiholzer U, Schlumpf M, Torresani T, Girard J. Carbohydrate metabolism is not impaired after 3 years of growth hormone therapy in children with Prader-Willi syndrome. Horm Res Paediatr  2003; 59(5): 239-48.
 [http://dx.doi.org/10.1159/000070224 ] [PMID: 12714788]

[159]
Rosenberg AGW, Passone CGB, Pellikaan K, et al. Growth hormone treatment for adults with prader-willi syndrome: a meta-analysis. J Clin Endocrinol Metab  2021; 106(10): 3068-91.
 [http://dx.doi.org/10.1210/clinem/dgab406 ] [PMID: 34105729]

[160]
Haqq AM, Muehlbauer MJ, Newgard CB, Grambow S, Freemark M. The metabolic phenotype of Prader-Willi syndrome (PWS) in childhood: Heightened insulin sensitivity relative to body mass index. J Clin Endocrinol Metab  2011; 96(1): E225-32.
 [http://dx.doi.org/10.1210/jc.2010-1733 ] [PMID: 20962018]

[161]
Cadoudal T, Buléon M, Sengenès C, et al. Impairment of adipose tissue in Prader–Willi syndrome rescued by growth hormone treatment. Int J Obes  2014; 38(9): 1234-40.
 [http://dx.doi.org/10.1038/ijo.2014.3 ] [PMID: 24406482]

[162]
Lacroix D, Moutel S, Coupaye M, et al. Metabolic and adipose tissue signatures in adults with Prader-Willi syndrome: A model of extreme adiposity. J Clin Endocrinol Metab  2015; 100(3): 850-9.
 [http://dx.doi.org/10.1210/jc.2014-3127 ] [PMID: 25478934]

[163]
Fintini D, Grugni G, Bocchini S, et al. Disorders of glucose metabolism in Prader–Willi syndrome: Results of a multicenter Italian cohort study. Nutr Metab Cardiovasc Dis  2016; 26(9): 842-7.
 [http://dx.doi.org/10.1016/j.numecd.2016.05.010 ] [PMID: 27381990]

[164]
Yang A, Kim J, Cho SY, Jin DK. Prevalence and risk factors for type 2 diabetes mellitus with Prader–Willi syndrome: A single center experience. Orphanet J Rare Dis  2017; 12(1): 146.
 [http://dx.doi.org/10.1186/s13023-017-0702-5 ] [PMID: 28854950]

[165]
Schuster DP, Osei K, Zipf WB. Characterization of alterations in glucose and insulin metabolism in Prader-Willi subjects. Metabolism  1996; 45(12): 1514-20.
 [http://dx.doi.org/10.1016/S0026-0495(96)90181-X ] [PMID: 8969285]

[166]
Eiholzer U, Stutz K, Weinmann C, Torresani T, Molinari L, Prader A. Low insulin, IGF-I and IGFBP-3 levels in children with Prader-Labhart-Willi syndrome. Eur J Pediatr  1998; 157(11): 890-3.
 [http://dx.doi.org/10.1007/s004310050961 ] [PMID: 9835431]

[167]
Oliveira CRP, Salvatori R, Barreto-Filho JAS, et al. Insulin sensitivity and β-cell function in adults with lifetime, untreated isolated growth hormone deficiency. J Clin Endocrinol Metab  2012; 97(3): 1013-9.
 [http://dx.doi.org/10.1210/jc.2011-2590 ] [PMID: 22170707]

[168]
Vicente TAR, Rocha ÍES, Salvatori R, et al. Lifetime congenital isolated GH deficiency does not protect from the development of diabetes. Endocr Connect  2013; 2(2): 112-7.
 [http://dx.doi.org/10.1530/EC-13-0014 ] [PMID: 23795286]

[169]
Hedgeman E, Ulrichsen SP, Carter S, et al. Long-term health outcomes in patients with Prader–Willi Syndrome: A nationwide cohort study in Denmark. Int J Obes  2017; 41(10): 1531-8.
 [http://dx.doi.org/10.1038/ijo.2017.139 ] [PMID: 28634363]

[170]
Manzardo AM, Loker J, Heinemann J, Loker C, Butler MG. Survival trends from the Prader–Willi Syndrome Association (USA) 40-year mortality survey. Genet Med  2018; 20(1): 24-30.
 [http://dx.doi.org/10.1038/gim.2017.92 ] [PMID: 28682308]

[171]
Pacoricona Alfaro DL, Lemoine P, Ehlinger V, et al. Causes of death in Prader-Willi syndrome: Lessons from 11 years’ experience of a national reference center. Orphanet J Rare Dis  2019; 14(1): 238.
 [http://dx.doi.org/10.1186/s13023-019-1214-2 ] [PMID: 31684997]

[172]
Oral EA, Simha V, Ruiz E, et al. Leptin-replacement therapy for lipodystrophy. N Engl J Med  2002; 346(8): 570-8.
 [http://dx.doi.org/10.1056/NEJMoa012437 ] [PMID: 11856796]

[173]
Beltrand J, Beregszaszi M, Chevenne D, et al. Metabolic correction induced by leptin replacement treatment in young children with Berardinelli-Seip congenital lipoatrophy. Pediatrics  2007; 120(2): e291-6.
 [http://dx.doi.org/10.1542/peds.2006-3165 ] [PMID: 17671040]

[174]
Chan JL, Lutz K, Cochran E, et al. Clinical effects of long-term metreleptin treatment in patients with lipodystrophy. Endocr Pract  2011; 17(6): 922-32.
 [http://dx.doi.org/10.4158/EP11229.OR ] [PMID: 22068254]

[175]
Diker-Cohen T, Cochran E, Gorden P, Brown RJ. Partial and generalized lipodystrophy: Comparison of baseline characteristics and response to metreleptin. J Clin Endocrinol Metab  2015; 100(5): 1802-10.
 [http://dx.doi.org/10.1210/jc.2014-4491 ] [PMID: 25734254]

[176]
Brown RJ, Meehan CA, Cochran E, et al. Effects of metreleptin in pediatric patients with lipodystrophy. J Clin Endocrinol Metab  2017; 102(5): 1511-9.
 [http://dx.doi.org/10.1210/jc.2016-3628 ] [PMID: 28324110]

[177]
Sekizkardes H, Cochran E, Malandrino N, Garg A, Brown RJ. Efficacy of metreleptin treatment in familial partial lipodystrophy due to PPARG vs. LMNA pathogenic variants. J Clin Endocrinol Metab  2019; 104(8): 3068-76.
 [http://dx.doi.org/10.1210/jc.2018-02787 ] [PMID: 31194872]

[178]
Nguyen ML, Sachdev V, Burklow TR, et al. Leptin attenuates cardiac hypertrophy in patients with generalized lipodystrophy. J Clin Endocrinol Metab  2021; 106(11): e4327-39.
 [http://dx.doi.org/10.1210/clinem/dgab499 ] [PMID: 34223895]

[179]
Mosbah H, Vantyghem MC, Nobécourt E, et al. Therapeutic indications and metabolic effects of metreleptin in patients with lipodystrophy syndromes: Real‐life experience from a national reference network. Diabetes Obes Metab  2022; 24(8): 1565-77.
 [http://dx.doi.org/10.1111/dom.14726 ] [PMID: 35445532]

[180]
Lima JG, Nobrega LHC, Lima NN, et al. Causes of death in patients with Berardinelli-Seip congenital generalized lipodystrophy. PLoS One  2018; 13(6): e0199052.
 [http://dx.doi.org/10.1371/journal.pone.0199052 ] [PMID: 29883474]

[181]
Montenegro Junior RM, Lima GECP, Fernandes VO, et al. Leu124Serfs*26, a novel AGPAT2 mutation in congenital generalized lipodystrophy with early cardiovascular complications. Diabetol Metab Syndr  2020; 12(1): 28.
 [http://dx.doi.org/10.1186/s13098-020-00538-y ] [PMID: 32280377]

[182]
Simha V, Garg A. Phenotypic heterogeneity in body fat distribution in patients with congenital generalized lipodystrophy caused by mutations in the AGPAT2 or seipin genes. J Clin Endocrinol Metab  2003; 88(11): 5433-7.
 [http://dx.doi.org/10.1210/jc.2003-030835 ] [PMID: 14602785]

[183]
Agarwal AK, Simha V, Oral EA, et al. Phenotypic and genetic heterogeneity in congenital generalized lipodystrophy. J Clin Endocrinol Metab  2003; 88(10): 4840-7.
 [http://dx.doi.org/10.1210/jc.2003-030855 ] [PMID: 14557463]

[184]
Yamamoto A, Kusakabe T, Sato K, Tokizaki T, Sakurai K, Abe S. Seipin-linked congenital generalized lipodystrophy type 2: A rare case with multiple lytic and pseudo-osteopoikilosis lesions. Acta Radiol Open  2019; 8(12): 2058460119892407.

[185]
Kim CA, Delépine M, Boutet E, et al. Association of a homozygous nonsense caveolin-1 mutation with Berardinelli-Seip congenital lipodystrophy. J Clin Endocrinol Metab  2008; 93(4): 1129-34.
 [http://dx.doi.org/10.1210/jc.2007-1328 ] [PMID: 18211975]

[186]
Schrauwen I, Szelinger S, Siniard AL, et al. A Frame-Shift Mutation in CAV1 Is Associated with a Severe Neonatal Progeroid and Lipodystrophy Syndrome. PLoS One  2015; 10(7): e0131797.
 [http://dx.doi.org/10.1371/journal.pone.0131797 ] [PMID: 26176221]

[187]
Karhan AN, Zammouri J, Auclair M, et al. Biallelic CAV1 null variants induce congenital generalized lipodystrophy with achalasia. Eur J Endocrinol  2021; 185(6): 841-54.
 [http://dx.doi.org/10.1530/EJE-21-0915 ] [PMID: 34643546]

[188]
Cao H, Alston L, Ruschman J, Hegele RA. Heterozygous CAV1 frameshift mutations (MIM 601047) in patients with atypical partial lipodystrophy and hypertriglyceridemia. Lipids Health Dis  2008; 7(1): 3.
 [http://dx.doi.org/10.1186/1476-511X-7-3 ] [PMID: 18237401]

[189]
Hayashi YK, Matsuda C, Ogawa M, et al. Human PTRF mutations cause secondary deficiency of caveolins resulting in muscular dystrophy with generalized lipodystrophy. J Clin Invest  2009; 119(9): 2623-33.
 [http://dx.doi.org/10.1172/JCI38660 ] [PMID: 19726876]

[190]
Rajab A, Straub V, McCann LJ, et al. Fatal cardiac arrhythmia and long-QT syndrome in a new form of congenital generalized lipodystrophy with muscle rippling (CGL4) due to PTRF-CAVIN mutations. PLoS Genet  2010; 6(3): e1000874.
 [http://dx.doi.org/10.1371/journal.pgen.1000874 ] [PMID: 20300641]

[191]
Nilay Güneş, Kutlu T, Tekant GT. et al.Congenital generalized lipodystrophy: The evaluation of clinical follow-up findings in a series of five patients with type 1 and two patients with type 4. Eur J Med Genet  2020; 63(4): 103819.
 [http://dx.doi.org/10.1016/j.ejmg.2019.103819 ] [PMID: 31778856]

[192]
Adiyaman SC. Congenital generalized lipodystrophy type 4 due to a novel PTRF/CAVIN1 pathogenic variant in a child: Effects of metreleptin substitution. J Pediatr Endocrinol Metab  2022; 35(7): 946-52.

[193]
Patni N, Vuitch F, Garg A. Postmortem Findings in a Young Man With Congenital Generalized Lipodystrophy, Type 4 Due to CAVIN1 Mutations. J Clin Endocrinol Metab  2019; 104(3): 957-60.
 [http://dx.doi.org/10.1210/jc.2018-01331 ] [PMID: 30476128]

[194]
Knebel B, Kotzka J, Lehr S, et al. A mutation in the c-Fos gene associated with congenital generalized lipodystrophy. Orphanet J Rare Dis  2013; 8(1): 119.
 [http://dx.doi.org/10.1186/1750-1172-8-119 ] [PMID: 23919306]

[195]
Treiber G, Flaus Furmaniuk A, Guilleux A, et al. A recurrent familial partial lipodystrophy due to a monoallelic or biallelic LMNA founder variant highlights the multifaceted cardiac manifestations of metabolic laminopathies. Eur J Endocrinol  2021; 185(4): 453-62.
 [http://dx.doi.org/10.1530/EJE-21-0282 ] [PMID: 34292171]

[196]
Kadowaki T, Kadowaki H, Rechler MM, et al. Five mutant alleles of the insulin receptor gene in patients with genetic forms of insulin resistance. J Clin Invest  1990; 86(1): 254-64.
 [http://dx.doi.org/10.1172/JCI114693 ] [PMID: 2365819]

[197]
Musso C, Cochran E, Moran SA, et al. Clinical course of genetic diseases of the insulin receptor (type A and Rabson-Mendenhall syndromes): A 30-year prospective. Medicine (Baltimore)  2004; 83(4): 209-22.
 [http://dx.doi.org/10.1097/01.md.0000133625.73570.54 ] [PMID: 15232309]

[198]
Semple RK, Sleigh A, Murgatroyd PR, et al. Postreceptor insulin resistance contributes to human dyslipidemia and hepatic steatosis. J Clin Invest  2009; 119(2): 315-22.
 [http://dx.doi.org/10.1172/JCI37432 ] [PMID: 19164855]

[199]
Iwanishi M, Kusakabe T, Azuma C, et al. Clinical characteristics in two patients with partial lipodystrophy and Type A insulin resistance syndrome due to a novel heterozygous missense mutation in the insulin receptor gene. Diabetes Res Clin Pract  2019; 152: 79-87.
 [http://dx.doi.org/10.1016/j.diabres.2019.04.034 ] [PMID: 31102683]

[200]
Al-Hussaini AA, Sulaiman NM, AlZahrani MD, Alenizi AS, Khan M. Prevalence of hepatopathy in type 1 diabetic children. BMC Pediatr  2012; 12(1): 160.
 [http://dx.doi.org/10.1186/1471-2431-12-160 ] [PMID: 23039762]

[201]
El-Karaksy HM, Anwar G, Esmat G, et al. Prevalence of hepatic abnormalities in a cohort of Egyptian children with type 1 diabetes mellitus. Pediatr Diabetes  2010; 11(7): 462-70.
 [http://dx.doi.org/10.1111/j.1399-5448.2009.00627.x ] [PMID: 20042012]

[202]
Ogilvy-Stuart AL, Soos MA, Hands SJ, Anthony MY, Dunger DB, O’Rahilly S. Hypoglycemia and resistance to ketoacidosis in a subject without functional insulin receptors. J Clin Endocrinol Metab  2001; 86(7): 3319-26.
 [http://dx.doi.org/10.1210/jcem.86.7.7631 ] [PMID: 11443207]

[203]
Brown RJ, Cochran E, Gorden P. Metreleptin improves blood glucose in patients with insulin receptor mutations. J Clin Endocrinol Metab  2013; 98(11): E1749-56.
 [http://dx.doi.org/10.1210/jc.2013-2317 ] [PMID: 23969187]

[204]
Tuhan H, Ceylaner S, Nalbantoğlu Ö. et al.A Mutation in INSR in a child presenting with severe acanthosis nigricans. J Clin Res Pediatr Endocrinol  2017; 9(4): 371-4.
 [http://dx.doi.org/10.4274/jcrpe.4577 ] [PMID: 28663160]

[205]
Güemes M, Rahman SA, Shah P, Hussain K. Enteroinsular hormones in two siblings with donohue syndrome and complete leptin deficiency. Pediatr Diabetes  2018; 19(4): 675-9.
 [http://dx.doi.org/10.1111/pedi.12619 ] [PMID: 29226618]

[206]
Rojek A, Wikiera B, Noczynska A, Niedziela M. Syndrome of congenital insulin resistance caused by a novel INSR gene mutation. J Clin Res Pediatr Endocrinol  2021; 0(0): 0.
 [http://dx.doi.org/10.4274/jcrpe.galenos.2021.2021.0256] [PMID: 34965699]

[207]
Longo N, Singh R, Griffin LD, Langley SD, Parks JS, Elsas LJ. Impaired growth in Rabson-Mendenhall syndrome: Lack of effect of growth hormone and insulin-like growth factor-I. J Clin Endocrinol Metab  1994; 79(3): 799-805.
 [http://dx.doi.org/10.1210/jcem.79.3.8077364 ] [PMID: 8077364]

[208]
Kirel B. Bozdağ O, Köşger P, Aydoğdu SD, Alincak E, Tekin N. A case of Donohue syndrome “Leprechaunism” with a novel mutation in the insulin receptor gene. Turk Pediatri Ars  2018; 52(4): 226-30.
 [http://dx.doi.org/10.5152/TurkPediatriArs.2017.3193 ] [PMID: 29483803]

[209]
Takasawa K, Tsuji-Hosokawa A, Takishima S, et al. Clinical characteristics of adolescent cases with Type A insulin resistance syndrome caused by heterozygous mutations in the β-subunit of the insulin receptor (INSR) gene. J Diabetes  2019; 11(1): 46-54.
 [http://dx.doi.org/10.1111/1753-0407.12797 ] [PMID: 29877041]

[210]
Verdecchia F, Akcan N, Dastamani A, Morgan K, Semple RK, Shah P. Unusual glycemic presentations in a child with a novel heterozygous intragenic INSR deletion. Horm Res Paediatr  2020; 93(6): 396-401.
 [http://dx.doi.org/10.1159/000510462 ] [PMID: 33040071]

[211]
Kapeller R, Chakrabarti R, Cantley L, Fay F, Corvera S. Internalization of activated platelet-derived growth factor receptor-phosphatidylinositol-3′ kinase complexes: Potential interactions with the microtubule cytoskeleton. Mol Cell Biol  1993; 13(10): 6052-63.
 [http://dx.doi.org/10.1128/mcb.13.10.6052-6063.1993 ] [PMID: 8413207]

[212]
Schwingshandl J, Mache CJ, Rath K, Borkenstein MH. SHORT syndrome and insulin resistance. Am J Med Genet  1993; 47(6): 907-9.
 [http://dx.doi.org/10.1002/ajmg.1320470619 ] [PMID: 8279490]

[213]
Dyment DA, Smith AC, Alcantara D, et al. Mutations in PIK3R1 cause SHORT syndrome. Am J Hum Genet  2013; 93(1): 158-66.
 [http://dx.doi.org/10.1016/j.ajhg.2013.06.005 ] [PMID: 23810382]

[214]
Chudasama KK, Winnay J, Johansson S, et al. SHORT syndrome with partial lipodystrophy due to impaired phosphatidylinositol 3 kinase signaling. Am J Hum Genet  2013; 93(1): 150-7.
 [http://dx.doi.org/10.1016/j.ajhg.2013.05.023 ] [PMID: 23810379]

[215]
Thauvin-Robinet C, Auclair M, Duplomb L, et al. PIK3R1 mutations cause syndromic insulin resistance with lipoatrophy. Am J Hum Genet  2013; 93(1): 141-9.
 [http://dx.doi.org/10.1016/j.ajhg.2013.05.019 ] [PMID: 23810378]

[216]
Schroeder C, Riess A, Bonin M, et al. PIK3R1 mutations in SHORT syndrome. Clin Genet  2014; 86(3): 292-4.
 [http://dx.doi.org/10.1111/cge.12263 ] [PMID: 23980586]

[217]
George S, Rochford JJ, Wolfrum C, et al. A family with severe insulin resistance and diabetes due to a mutation in AKT2. Science  2004; 304(5675): 1325-8.
 [http://dx.doi.org/10.1126/science.1096706 ] [PMID: 15166380]

[218]
Tan K, Kimber WA, Luan J, et al. Analysis of genetic variation in Akt2/PKB-beta in severe insulin resistance, lipodystrophy, type 2 diabetes, and related metabolic phenotypes. Diabetes  2007; 56(3): 714-9.
 [http://dx.doi.org/10.2337/db06-0921 ] [PMID: 17327441]

[219]
Sun XQ, Luo YY, An LW, et al. Contribution of the Akt2 gene to type 2 diabetes in the Chinese Han population. Chin Med J (Engl)  2011; 124(5): 725-8.
 [PMID: 21518566]

[220]
Murdocca M, Spitalieri P, De Masi C, et al. Functional analysis of POLD1 p.ser605del variant: The aging phenotype of MDPL syndrome is associated with an impaired DNA repair capacity. Aging (Albany NY)  2021; 13(4): 4926-45.
 [http://dx.doi.org/10.18632/aging.202680 ] [PMID: 33618333]

[221]
Speckman RA, Garg A, Du F, et al. Mutational and haplotype analyses of families with familial partial lipodystrophy (Dunnigan variety) reveal recurrent missense mutations in the globular C-terminal domain of lamin A/C. Am J Hum Genet  2000; 66(4): 1192-8.
 [http://dx.doi.org/10.1086/302836 ] [PMID: 10739751]

[222]
Cao H, Hegele RA. Nuclear lamin A/C R482Q mutation in Canadian kindreds with Dunnigan-type familial partial lipodystrophy. Hum Mol Genet  2000; 9(1): 109-12.
 [http://dx.doi.org/10.1093/hmg/9.1.109 ] [PMID: 10587585]

[223]
Vantyghem MC, Pigny P, Maurage CA, et al. Patients with familial partial lipodystrophy of the Dunnigan type due to a LMNA R482W mutation show muscular and cardiac abnormalities. J Clin Endocrinol Metab  2004; 89(11): 5337-46.
 [http://dx.doi.org/10.1210/jc.2003-031658 ] [PMID: 15531479]

[224]
Pandey SN, Pungavkar SA, Vaidya RA, et al. An imaging study of body composition including lipodeposition pattern in a patient of familial partial lipodystrophy (Dunnigan type). J Assoc Physicians India  2005; 53: 897-900.
 [PMID: 16459536]

[225]
Monteiro L, Foss-Freitas M, Montenegro RM, Foss M. Body fat distribution in women with familial partial lipodystrophy caused by mutation in the lamin A/C gene. Indian J Endocrinol Metab  2012; 16(1): 136-8.
 [http://dx.doi.org/10.4103/2230-8210.91209 ] [PMID: 22276265]

[226]
Wong SPY, Huda M, English P, et al. Adipokines and the insulin resistance syndrome in familial partial lipodystrophy caused by a mutation in lamin A/C. Diabetologia  2005; 48(12): 2641-9.
 [http://dx.doi.org/10.1007/s00125-005-0038-x ] [PMID: 16320084]

[227]
Haque WA, Vuitch F, Garg A. Post-mortem findings in familial partial lipodystrophy, Dunnigan variety. Diabet Med  2002; 19(12): 1022-5.
 [http://dx.doi.org/10.1046/j.1464-5491.2002.00796.x ] [PMID: 12647844]

[228]
Lüdtke A, Roos GM, van Hettinga M, Horst BAJ, Worman HJ, Schmidt HHJ. Post-mortem findings in Dunnigan-type familial partial lipodystrophy. Diabet Med  2010; 27(2): 245-6.
 [http://dx.doi.org/10.1111/j.1464-5491.2009.02909.x ] [PMID: 20546275]

[229]
Subramanyam L, Simha V, Garg A. Overlapping syndrome with familial partial lipodystrophy, Dunnigan variety and cardiomyopathy due to amino-terminal heterozygous missense lamin A/C mutations. Clin Genet  2010; 78(1): 66-73.
 [http://dx.doi.org/10.1111/j.1399-0004.2009.01350.x ] [PMID: 20041886]

[230]
Owen KR, Donohoe M, Ellard S, et al. Mesangiocapillary glomerulonephritis type 2 associated with familial partial lipodystrophy (Dunnigan-Kobberling syndrome). Nephron Clin Pract  2004; 96(2): c35-8.
 [http://dx.doi.org/10.1159/000076396 ] [PMID: 14988595]

[231]
Imachi H, Murao K, Ohtsuka S, et al. A case of Dunnigan-type familial partial lipodystrophy (FPLD) due to lamin A/C (LMNA) mutations complicated by end-stage renal disease. Endocrine  2009; 35(1): 18-21.
 [http://dx.doi.org/10.1007/s12020-008-9127-1 ] [PMID: 19011997]

[232]
Thong KM, Xu Y, Cook J, et al. Cosegregation of focal segmental glomerulosclerosis in a family with familial partial lipodystrophy due to a mutation in LMNA. Nephron Clin Pract  2013; 124(1-2): 31-7.
 [http://dx.doi.org/10.1159/000354716 ] [PMID: 24080738]

[233]
Fountas A, Giotaki Z, Dounousi E, et al. Familial partial lipodystrophy and proteinuric renal disease due to a missense c.1045C > T LMNA mutation. Endocrinol Diabetes Metab Case Rep  2017; 2017: 0049.
 [http://dx.doi.org/10.1530/EDM-17-0049] [PMID: 28620495]

[234]
Soyaltin UE, Simsir IY, Akinci B, et al. Homozygous LMNA p.R582H pathogenic variant reveals increasing effect on the severity of fat loss in lipodystrophy. Clin Diabetes Endocrinol  2020; 6: 13.

[235]
Agarwal AK, Fryns JP, Auchus RJ, Garg A. Zinc metalloproteinase, ZMPSTE24, is mutated in mandibuloacral dysplasia. Hum Mol Genet  2003; 12(16): 1995-2001.
 [http://dx.doi.org/10.1093/hmg/ddg213 ] [PMID: 12913070]

[236]
Hitzert MM, van der Crabben SN, Baldewsingh G, et al. Mandibuloacral dysplasia type B (MADB): A cohort of eight patients from Suriname with a homozygous founder mutation in ZMPSTE24 (FACE1), clinical diagnostic criteria and management guidelines. Orphanet J Rare Dis  2019; 14(1): 294.
 [http://dx.doi.org/10.1186/s13023-019-1269-0 ] [PMID: 31856865]

[237]
Freidenberg GR, Cutler DL, Jones MC, et al. Severe insulin resistance and diabetes mellitus in mandibuloacral dysplasia. Arch Pediatr Adolesc Med  1992; 146(1): 93-9.
 [http://dx.doi.org/10.1001/archpedi.1992.02160130095028 ] [PMID: 1736653]

[238]
Epstkin CJ, Martin GM, Schultz AL, Motulskys AG. Werner’s syndrome a review of its symptomatology, natural history, pathologic features, genetics and relationship to the natural aging process. Medicine (Baltimore)  1966; 45(3): 177-221.
 [http://dx.doi.org/10.1097/00005792-196605000-00001 ] [PMID: 5327241]

[239]
Peng H, Wang J, Liu Y, et al. Case Report: A novel WRN mutation in Werner syndrome patient with diabetic foot disease and myelodysplastic syndrome. Front Endocrinol (Lausanne)  2022; 13: 918979.
 [http://dx.doi.org/10.3389/fendo.2022.918979 ] [PMID: 35909544]

[240]
Lauper JM, Krause A, Vaughan TL, Monnat RJ Jr. Spectrum and risk of neoplasia in Werner syndrome: A systematic review. PLoS One  2013; 8(4): e59709.
 [http://dx.doi.org/10.1371/journal.pone.0059709 ] [PMID: 23573208]

[241]
Smith U, Digirolamo M, Blohmé G, Kral JG, Tisell LE. Possible systemic metabolic effects of regional adiposity in a patient with Werner’s syndrome. Int J Obes  1980; 4(2): 153-63.
 [PMID: 6995362]

[242]
Mori S, Murano S, Yokote K, et al. Enhanced intra-abdominal visceral fat accumulation in patients with Werner’s syndrome. Int J Obes  2001; 25(2): 292-5.
 [http://dx.doi.org/10.1038/sj.ijo.0801529 ] [PMID: 11410834]

[243]
Yokote K, Honjo S, Kobayashi K, et al. Metabolic improvement and abdominal fat redistribution in Werner syndrome by pioglitazone. J Am Geriatr Soc  2004; 52(9): 1582-3.
 [http://dx.doi.org/10.1111/j.1532-5415.2004.52430_4.x ] [PMID: 15341572]

[244]
Honjo S, Yokote K, Fujishiro T, et al. Early amelioration of insulin resistance and reduction of interleukin-6 in Werner syndrome using pioglitazone. J Am Geriatr Soc  2008; 56(1): 173-4.
 [http://dx.doi.org/10.1111/j.1532-5415.2007.01484.x ] [PMID: 18184212]

[245]
Blohmé G, Smith U. Metabolic studies in a case of Werner’s syndrome. Diabete Metab  1979; 5(2): 119-24.
 [PMID: 478081]

[246]
Yamada K, Ikegami H, Yoneda H, Miki T, Ogihara T. All patients with Werner’s syndrome are insulin resistant, but only those who also have impaired insulin secretion develop overt diabetes. Diabetes Care  1999; 22(12): 2094-5.
 [http://dx.doi.org/10.2337/diacare.22.12.2094 ] [PMID: 10587857]

[247]
Abe T, Yamaguchi Y, Izumino K, et al. Evaluation of insulin response in glucose tolerance test in a patient with Werner’s syndrome: A 16-year follow-up study. Diabetes Nutr Metab  2000; 13(2): 113-8.
 [PMID: 10898130]

[248]
Okabe E, Takemoto M, Onishi S, et al. Incidence and characteristics of metabolic disorders and vascular complications in individuals with Werner syndrome in Japan. J Am Geriatr Soc  2012; 60(5): 997-8.
 [http://dx.doi.org/10.1111/j.1532-5415.2012.03944.x ] [PMID: 22587870]

[249]
Takemoto M, Kubota Y, Taniguchi T, et al. Management guideline for Werner syndrome. Diabetes associated with Werner syndrome. Geriatr Gerontol Int  2021; 21(2): 142-5.
 [http://dx.doi.org/10.1111/ggi.14083 ] [PMID: 33169495]

[250]
Atallah I, McCormick D, Good JM, et al. Partial lipodystrophy, severe dyslipidaemia and insulin resistant diabetes as early signs of Werner syndrome. J Clin Lipidol  2022; 16(5): 583-90.
 [http://dx.doi.org/10.1016/j.jacl.2022.06.004 ] [PMID: 35780059]

[251]
Wang X, Liu S, Qin F, Liu Q, Wang Q. Werner syndrome presenting as early-onset diabetes: A case report. J Diabetes Investig  2022; 13(3): 592-8.
 [http://dx.doi.org/10.1111/jdi.13682]

[252]
Watanabe K, Kobayashi K, Takemoto M, et al. Sitagliptin improves postprandial hyperglycemia by inhibiting glucagon secretion in Werner syndrome with diabetes. Diabetes Care  2013; 36(8): e119.
 [http://dx.doi.org/10.2337/dc13-0709 ] [PMID: 23881973]

[253]
Yamaga M, Takemoto M, Shoji M, et al. Werner syndrome: A model for sarcopenia due to accelerated aging. Aging  2017; 9(7): 1738-44.
 [http://dx.doi.org/10.18632/aging.101265 ] [PMID: 28738022]

[254]
Tanaka F, Kuzuya M. Examination of the body composition of patients with Werner syndrome using bioelectrical impedance analysis. Geriatr Gerontol Int  2022; 22(1): 75-80.
 [http://dx.doi.org/10.1111/ggi.14310 ] [PMID: 34841636]

[255]
Weedon MN, Ellard S, Prindle MJ, et al. An in-frame deletion at the polymerase active site of POLD1 causes a multisystem disorder with lipodystrophy. Nat Genet  2013; 45(8): 947-50.
 [http://dx.doi.org/10.1038/ng.2670 ] [PMID: 23770608]

[256]
Gladys B, René W, Anabelle D, et al. Child to adulthood clinical description of MDPL syndrome due to a novel variant in POLD1. Eur J Med Genet  2021; 64(12): 104333.
 [http://dx.doi.org/10.1016/j.ejmg.2021.104333 ] [PMID: 34517090]

[257]
Bappy MNI, Roy A, Rabbi MGR, et al. Scrutinizing Deleterious Nonsynonymous SNPs and Their Effect on Human POLD1 Gene. Genet Res  2022; 2022: 1-12.
 [http://dx.doi.org/10.1155/2022/1740768 ] [PMID: 35620275]

[258]
Kamath-Loeb AS, Johansson E, Burgers PMJ, Loeb LA. Functional interaction between the Werner Syndrome protein and DNA polymerase δ. Proc Natl Acad Sci USA  2000; 97(9): 4603-8.
 [http://dx.doi.org/10.1073/pnas.97.9.4603 ] [PMID: 10781066]

[259]
Kamath-Loeb AS, Shen JC, Schmitt MW, Loeb LA. The Werner syndrome exonuclease facilitates DNA degradation and high fidelity DNA polymerization by human DNA polymerase δ J Biol Chem  2012; 287(15): 12480-90.
 [http://dx.doi.org/10.1074/jbc.M111.332577 ] [PMID: 22351772]

[260]
Chen T, Li M, Wu H, et al. Short stature as the first manifestation of mandibular hypoplasia, deafness, progeroid feature and lipodystrophy (MDPL) syndrome. Int J Clin Exp Med  2017; 10(2): 3876-83.

[261]
Elouej S, Beleza-Meireles A, Caswell R, et al. Exome sequencing reveals a de novo POLD1 mutation causing phenotypic variability in mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome (MDPL). Metabolism  2017; 71: 213-25.
 [http://dx.doi.org/10.1016/j.metabol.2017.03.011 ] [PMID: 28521875]

[262]
Shastry S, Simha V, Godbole K, et al. A novel syndrome of mandibular hypoplasia, deafness, and progeroid features associated with lipodystrophy, undescended testes, and male hypogonadism. J Clin Endocrinol Metab  2010; 95(10): E192-7.
 [http://dx.doi.org/10.1210/jc.2010-0419 ] [PMID: 20631028]

[263]
Sasaki H, Yanagi K, Ugi S, et al. Definitive diagnosis of mandibular hypoplasia, deafness, progeroid features and lipodystrophy (MDPL) syndrome caused by a recurrent <i>de novo</i> mutation in the <i>POLD1</i> gene. Endocr J  2018; 65(2): 227-38.
 [http://dx.doi.org/10.1507/endocrj.EJ17-0287 ] [PMID: 29199204]

[264]
German J, Sanz MM, Ciocci S, Ye TZ, Ellis NA. Syndrome-causing mutations of the BLM gene in persons in the Bloom’s Syndrome Registry. Hum Mutat  2007; 28(8): 743-53.
 [http://dx.doi.org/10.1002/humu.20501 ] [PMID: 17407155]

[265]
Gönenc II, Elcioglu NH, Martinez Grijalva C, et al. Phenotypic spectrum ofBLM ‐ andRMI1 ‐related Bloom syndrome. Clin Genet  2022; 101(5-6): 559-64.
 [http://dx.doi.org/10.1111/cge.14125 ] [PMID: 35218564]

[266]
Bloom D. Congenital telangiectatic erythema resembling lupus erythematosus in dwarfs; probably a syndrome entity. AMA Am J Dis Child  1954; 88(6): 754-8.
 [http://dx.doi.org/10.1001/archpedi.1954.02050100756008 ] [PMID: 13206391]

[267]
Diaz A, Vogiatzi MG, Sanz MM, German J. Evaluation of short stature, carbohydrate metabolism and other endocrinopathies in Bloom’s syndrome. Horm Res Paediatr  2006; 66(3): 111-7.
 [http://dx.doi.org/10.1159/000093826 ] [PMID: 16763388]

[268]
Farhan SMK, Robinson JF, McIntyre AD, et al. A novel LIPE nonsense mutation found using exome sequencing in siblings with late-onset familial partial lipodystrophy. Can J Cardiol  2014; 30(12): 1649-54.
 [http://dx.doi.org/10.1016/j.cjca.2014.09.007 ] [PMID: 25475467]

[269]
Garg A, Sankella S, Xing C, Agarwal AK. Whole-exome sequencing identifies ADRA2A mutation in atypical familial partial lipodystrophy. JCI Insight  2016; 1(9): e86870.
 [http://dx.doi.org/10.1172/jci.insight.86870 ] [PMID: 27376152]

[270]
Rubio-Cabezas O, Puri V, Murano I, et al. Partial lipodystrophy and insulin resistant diabetes in a patient with a homozygous nonsense mutation in CIDEC. EMBO Mol Med  2009; 1(5): 280-7.
 [http://dx.doi.org/10.1002/emmm.200900037 ] [PMID: 20049731]

[271]
Ito M, Nagasawa M, Hara T, Ide T, Murakami K. Differential roles of CIDEA and CIDEC in insulin-induced anti-apoptosis and lipid droplet formation in human adipocytes. J Lipid Res  2010; 51(7): 1676-84.
 [http://dx.doi.org/10.1194/jlr.M002147 ] [PMID: 20154362]

[272]
Ito M, Nagasawa M, Omae N, Ide T, Akasaka Y, Murakami K. Differential regulation of CIDEA and CIDEC expression by insulin via Akt1/2- and JNK2-dependent pathways in human adipocytes. J Lipid Res  2011; 52(8): 1450-60.
 [http://dx.doi.org/10.1194/jlr.M012427 ] [PMID: 21636835]

[273]
Gandotra S, Le Dour C, Bottomley W, et al. Perilipin deficiency and autosomal dominant partial lipodystrophy. N Engl J Med  2011; 364(8): 740-8.
 [http://dx.doi.org/10.1056/NEJMoa1007487 ] [PMID: 21345103]

[274]
Kozusko K, Tsang VHM, Bottomley W, et al. Clinical and molecular characterization of a novel PLIN1 frameshift mutation identified in patients with familial partial lipodystrophy. Diabetes  2015; 64(1): 299-310.
 [http://dx.doi.org/10.2337/db14-0104 ] [PMID: 25114292]

[275]
Laver TW, Patel KA, Colclough K, et al. PLIN1 haploinsufficiency is not associated with lipodystrophy. J Clin Endocrinol Metab  2018; 103(9): 3225-30.
 [http://dx.doi.org/10.1210/jc.2017-02662 ] [PMID: 30020498]

[276]
Patel KA, Burman S, Laver TW, Hattersley AT, Frayling TM, Weedon MN. PLIN1 haploinsufficiency causes a favorable metabolic profile. J Clin Endocrinol Metab  2022; 107(6): e2318-23.
 [http://dx.doi.org/10.1210/clinem/dgac104 ] [PMID: 35235652]

[277]
Graul-Neumann LM, Kienitz T, Robinson PN, et al. Marfan syndrome with neonatal progeroid syndrome-like lipodystrophy associated with a novel frameshift mutation at the 3′ terminus of the FBN1-gene. Am J Med Genet A  2010; 152A(11): 2749-55.
 [http://dx.doi.org/10.1002/ajmg.a.33690 ] [PMID: 20979188]

[278]
Horn D, Robinson PN. Progeroid facial features and lipodystrophy associated with a novel splice site mutation in the final intron of the FBN1 gene. Am J Med Genet A  2011; 155(4): 721-4.
 [http://dx.doi.org/10.1002/ajmg.a.33905 ] [PMID: 21594993]

[279]
Goldblatt J, Hyatt J, Edwards C, Walpole I. Further evidence for a marfanoid syndrome with neonatal progeroid features and severe generalized lipodystrophy due to frameshift mutations near the 3′ end of the FBN1 gene. Am J Med Genet A  2011; 155(4): 717-20.
 [http://dx.doi.org/10.1002/ajmg.a.33906 ] [PMID: 21594992]

[280]
Takenouchi T, Hida M, Sakamoto Y, et al. Severe congenital lipodystrophy and a progeroid appearance: Mutation in the penultimate exon of FBN1 causing a recognizable phenotype. Am J Med Genet A  2013; 161(12): 3057-62.
 [http://dx.doi.org/10.1002/ajmg.a.36157 ] [PMID: 24039054]

[281]
Garg A, Xing C. De novo heterozygous FBN1 mutations in the extreme C-terminal region cause progeroid fibrillinopathy. Am J Med Genet A  2014; 164(5): 1341-5.
 [http://dx.doi.org/10.1002/ajmg.a.36449 ] [PMID: 24665001]

[282]
Passarge E, Robinson PN, Graul-Neumann LM. Marfanoid–progeroid–lipodystrophy syndrome: A newly recognized fibrillinopathy. Eur J Hum Genet  2016; 24(9): 1244-7.
 [http://dx.doi.org/10.1038/ejhg.2016.6 ] [PMID: 26860060]

[283]
Boden G, Chen X, Mozzoli M, Ryan I. Effect of fasting on serum leptin in normal human subjects. J Clin Endocrinol Metab  1996; 81(9): 3419-23.
 [http://dx.doi.org/10.1210/jcem.81.9.8784108 ] [PMID: 8784108]

[284]
Considine RV, Sinha MK, Heiman ML, et al. Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med  1996; 334(5): 292-5.
 [http://dx.doi.org/10.1056/NEJM199602013340503 ] [PMID: 8532024]

[285]
Larsson H, Elmståhl S, Ahrén B. Plasma leptin levels correlate to islet function independently of body fat in postmenopausal women. Diabetes  1996; 45(11): 1580-4.
 [http://dx.doi.org/10.2337/diab.45.11.1580 ] [PMID: 8866564]

[286]
Al-Shoumer KAS, Anyaoku V, Richmond W, Johnston DG. Elevated leptin concentrations in growth hormone-deficient hypopituitary adults. Clin Endocrinol (Oxf)  1997; 47(2): 153-9.
 [http://dx.doi.org/10.1046/j.1365-2265.1997.2131054.x ] [PMID: 9302387]

[287]
Kolaczynski JW, Considine RV, Ohannesian J, et al. Responses of leptin to short-term fasting and refeeding in humans: A link with ketogenesis but not ketones themselves. Diabetes  1996; 45(11): 1511-5.
 [http://dx.doi.org/10.2337/diab.45.11.1511 ] [PMID: 8866554]

[288]
Sinha MK, Opentanova I, Ohannesian JP, et al. Evidence of free and bound leptin in human circulation. Studies in lean and obese subjects and during short-term fasting. J Clin Invest  1996; 98(6): 1277-82.
 [http://dx.doi.org/10.1172/JCI118913 ] [PMID: 8823291]

[289]
Hernández C, Simó R, Chacón P, et al. Influence of surgical stress and parenteral nutrition on serum leptin concentration. Clin Nutr  2000; 19(1): 61-4.
 [http://dx.doi.org/10.1054/clnu.1999.0075 ] [PMID: 10700536]

[290]
Dubuc GR, Phinney SD, Stern JS, Havel PJ. Changes of serum leptin and endocrine and metabolic parameters after 7 days of energy restriction in men and women. Metabolism  1998; 47(4): 429-34.
 [http://dx.doi.org/10.1016/S0026-0495(98)90055-5 ] [PMID: 9550541]

[291]
Kolaczynski JW, Ohannesian JP, Considine RV, Marco CC, Caro JF. Response of leptin to short-term and prolonged overfeeding in humans. J Clin Endocrinol Metab  1996; 81(11): 4162-5.
 [http://dx.doi.org/10.1210/jcem.81.11.8923877 ] [PMID: 8923877]

[292]
Montague CT, Farooqi IS, Whitehead JP, et al. Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature  1997; 387(6636): 903-8.
 [http://dx.doi.org/10.1038/43185 ] [PMID: 9202122]

[293]
Strobel A, Issad T, Camoin L, Ozata M, Strosberg AD. A leptin missense mutation associated with hypogonadism and morbid obesity. Nat Genet  1998; 18(3): 213-5.
 [http://dx.doi.org/10.1038/ng0398-213 ] [PMID: 9500540]

[294]
Gibson WT, Farooqi IS, Moreau M, et al. Congenital leptin deficiency due to homozygosity for the Delta133G mutation: Report of another case and evaluation of response to four years of leptin therapy. J Clin Endocrinol Metab  2004; 89(10): 4821-6.
 [http://dx.doi.org/10.1210/jc.2004-0376 ] [PMID: 15472169]

[295]
Mazen I, Amr K, Tantawy S, Farooqi IS, El Gammal M. A novel mutation in the leptin gene (W121X) in an Egyptian family. Mol Genet Metab Rep  2014; 1: 474-6.
 [http://dx.doi.org/10.1016/j.ymgmr.2014.10.002 ] [PMID: 27896126]

[296]
Ozsu E, Ceylaner S, Onay H. Early-onset severe obesity due to complete deletion of the leptin gene in a boy. J Pediatr Endocrinol Metab  2017; 30(11): 1227-30.
 [http://dx.doi.org/10.1515/jpem-2017-0063 ] [PMID: 29040067]

[297]
Yupanqui-Lozno H, Bastarrachea RA, Yupanqui-Velazco ME, et al. Congenital leptin deficiency and leptin gene missense mutation found in two colombian sisters with severe obesity. Genes (Basel)  2019; 10(5): 342.
 [http://dx.doi.org/10.3390/genes10050342 ] [PMID: 31067764]

[298]
Fırat SN, Onay H. Early-onset severe obesity due to homozygous p.R105W (c313C> T) mutation in leptin gene in Turkish siblings: Two cases reports. Obes Res Clin Pract  2021; 15(6): 600-3.
 [http://dx.doi.org/10.1016/j.orcp.2021.11.001 ] [PMID: 34802983]

[299]
Wabitsch M, Funcke JB, Lennerz B, et al. Biologically inactive leptin and early-onset extreme obesity. N Engl J Med  2015; 372(1): 48-54.
 [http://dx.doi.org/10.1056/NEJMoa1406653 ] [PMID: 25551525]

[300]
Heymsfield SB, Fong TM, Gantz I, Erondu N. Fat and energy partitioning: Longitudinal observations in leptin-treated adults homozygous for a Lep mutation. Obesity (Silver Spring)  2006; 14(2): 258-65.
 [http://dx.doi.org/10.1038/oby.2006.33 ] [PMID: 16571851]

[301]
Fischer-Posovszky P, von Schnurbein J, Moepps B, et al. A new missense mutation in the leptin gene causes mild obesity and hypogonadism without affecting T cell responsiveness. J Clin Endocrinol Metab  2010; 95(6): 2836-40.
 [http://dx.doi.org/10.1210/jc.2009-2466 ] [PMID: 20382689]

[302]
Farooqi IS, Jebb SA, Langmack G, et al. Effects of recombinant leptin therapy in a child with congenital leptin deficiency. N Engl J Med  1999; 341(12): 879-84.
 [http://dx.doi.org/10.1056/NEJM199909163411204 ] [PMID: 10486419]

[303]
Licinio J, Caglayan S, Ozata M, et al. Phenotypic effects of leptin replacement on morbid obesity, diabetes mellitus, hypogonadism, and behavior in leptin-deficient adults. Proc Natl Acad Sci USA  2004; 101(13): 4531-6.
 [http://dx.doi.org/10.1073/pnas.0308767101 ] [PMID: 15070752]

[304]
Farooqi IS, Matarese G, Lord GM, et al. Beneficial effects of leptin on obesity, T cell hyporesponsiveness, and neuroendocrine/metabolic dysfunction of human congenital leptin deficiency. J Clin Invest  2002; 110(8): 1093-103.
 [http://dx.doi.org/10.1172/JCI0215693 ] [PMID: 12393845]

[305]
Mazen I, El-Gammal M, Abdel-Hamid M, Amr K. A novel homozygous missense mutation of the leptin gene (N103K) in an obese Egyptian patient. Mol Genet Metab  2009; 97(4): 305-8.
 [http://dx.doi.org/10.1016/j.ymgme.2009.04.002 ] [PMID: 19427251]

[306]
Paz-Filho G, Mastronardi C, Delibasi T, Wong ML, Licinio J. Congenital leptin deficiency: Diagnosis and effects of leptin replacement therapy. Arq Bras Endocrinol Metabol  2010; 54(8): 690-7.
 [http://dx.doi.org/10.1590/S0004-27302010000800005 ] [PMID: 21340154]

[307]
von Schnurbein J, Heni M, Moss A, et al. Rapid improvement of hepatic steatosis after initiation of leptin substitution in a leptin-deficient girl. Horm Res Paediatr  2013; 79(5): 310-7.
 [http://dx.doi.org/10.1159/000348541 ] [PMID: 23651953]

[308]
Brandt S, von Schnurbein J, Denzer C, Kratzer W, Wabitsch M. Lower circulating leptin levels are related to non-alcoholic fatty liver disease in children with obesity. Front Endocrinol (Lausanne)  2022; 13: 881982.
 [http://dx.doi.org/10.3389/fendo.2022.881982 ] [PMID: 35677722]

[309]
Paz-Filho GJ, Delibasi T, Erol HK, Wong ML, Licinio J. Cellular immunity before and after leptin replacement therapy. J Pediatr Endocrinol Metab  2009; 22(11): 1069-74.
 [http://dx.doi.org/10.1515/JPEM.2009.22.11.1069 ] [PMID: 20101893]

[310]
Farooqi IS, Wangensteen T, Collins S, et al. Clinical and molecular genetic spectrum of congenital deficiency of the leptin receptor. N Engl J Med  2007; 356(3): 237-47.
 [http://dx.doi.org/10.1056/NEJMoa063988 ] [PMID: 17229951]

[311]
Huvenne H, Le Beyec J, Pépin D, et al. Seven novel deleterious LEPR mutations found in early-onset obesity: A ΔExon6-8 shared by subjects from Reunion Island, France, suggests a founder effect. J Clin Endocrinol Metab  2015; 100(5): E757-66.
 [http://dx.doi.org/10.1210/jc.2015-1036 ] [PMID: 25751111]

[312]
Clément K, Vaisse C, Lahlou N, et al. A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction. Nature  1998; 392(6674): 398-401.
 [http://dx.doi.org/10.1038/32911 ] [PMID: 9537324]

[313]
Andiran N, Çelik N, Andiran F. Homozygosity for two missense mutations in the leptin receptor gene (P316T;W646C) in a Turkmenian girl with severe early-onset obesity. J Pediatr Endocrinol Metab  2011; 24(11-12): 1043-5.
 [http://dx.doi.org/10.1515/JPEM.2011.313 ] [PMID: 22308862]

[314]
Mazen I, El-Gammal M, Abdel-Hamid M, Farooqi IS, Amr K. Homozygosity for a novel missense mutation in the leptin receptor gene (P316T) in two Egyptian cousins with severe early onset obesity. Mol Genet Metab  2011; 102(4): 461-4.
 [http://dx.doi.org/10.1016/j.ymgme.2010.12.013 ] [PMID: 21306929]

[315]
Le Beyec J, Cugnet-Anceau C, Pépin D, et al. Homozygous leptin receptor mutation due to uniparental disomy of chromosome 1: Response to bariatric surgery. J Clin Endocrinol Metab  2013; 98(2): E397-402.
 [http://dx.doi.org/10.1210/jc.2012-2779 ] [PMID: 23275530]

[316]
Niazi RK, Gjesing AP, Hollensted M, et al. Identification of novel LEPR mutations in Pakistani families with morbid childhood obesity. BMC Med Genet  2018; 19(1): 199.
 [http://dx.doi.org/10.1186/s12881-018-0710-x ] [PMID: 30442103]

[317]
Nunziata A, Funcke JB, Borck G, et al. Functional and phenotypic characteristics of human leptin receptor mutations. J Endocr Soc  2019; 3(1): 27-41.
 [http://dx.doi.org/10.1210/js.2018-00123 ] [PMID: 30560226]

[318]
Armağan C, Yılmaz C, Koç A. et al.A toddler with a novel LEPR mutation. Hormones (Athens)  2019; 18(2): 237-40.
 [http://dx.doi.org/10.1007/s42000-019-00097-6] [PMID: 30778850]

[319]
Zorn S, von Schnurbein J, Kohlsdorf K, Denzer C, Wabitsch M. Diagnostic and therapeutic odyssey of two patients with compound heterozygous leptin receptor deficiency. Mol Cell Pediatr  2020; 7(1): 15.
 [http://dx.doi.org/10.1186/s40348-020-00107-3 ] [PMID: 33140236]

[320]
Voigtmann F, Wolf P, Landgraf K, et al. Identification of a novel leptin receptor (LEPR) variant and proof of functional relevance directing treatment decisions in patients with morbid obesity. Metabolism  2021; 116: 154438.
 [http://dx.doi.org/10.1016/j.metabol.2020.154438 ] [PMID: 33221380]

[321]
Chaves C, Kay T, Anselmo J. Early onset obesity due to a mutation in the human leptin receptor gene. Endocrinol Diabetes Metab Case Rep  2022; 2022: 21-0124.
 [http://dx.doi.org/10.1530/EDM-21-0124 ] [PMID: 36001025]

[322]
Brandt S, Schnurbein J, Lennerz B, et al. Methylphenidate in children with monogenic obesity due to LEPR or MC4R deficiency improves feeling of satiety and reduces BMI‐SDS—A case series. Pediatr Obes  2020; 15(1): e12577.
 [http://dx.doi.org/10.1111/ijpo.12577 ] [PMID: 31670905]

[323]
Clément K, van den Akker E, Argente J, et al. Efficacy and safety of setmelanotide, an MC4R agonist, in individuals with severe obesity due to LEPR or POMC deficiency: Single-arm, open-label, multicentre, phase 3 trials. Lancet Diabetes Endocrinol  2020; 8(12): 960-70.
 [http://dx.doi.org/10.1016/S2213-8587(20)30364-8 ] [PMID: 33137293]

[324]
Krude H, Biebermann H, Luck W, Horn R, Brabant G, Grüters A. Severe early-onset obesity, adrenal insufficiency and red hair pigmentation caused by POMC mutations in humans. Nat Genet  1998; 19(2): 155-7.
 [http://dx.doi.org/10.1038/509 ] [PMID: 9620771]

[325]
Yeo GSH, Farooqi IS, Aminian S, Halsall DJ, Stanhope RG, O’Rahilly S. A frameshift mutation in MC4R associated with dominantly inherited human obesity. Nat Genet  1998; 20(2): 111-2.
 [http://dx.doi.org/10.1038/2404 ] [PMID: 9771698]

[326]
Vaisse C, Clement K, Guy-Grand B, Froguel P. A frameshift mutation in human MC4R is associated with a dominant form of obesity. Nat Genet  1998; 20(2): 113-4.
 [http://dx.doi.org/10.1038/2407 ] [PMID: 9771699]

[327]
Farooqi IS, Yeo GSH, Keogh JM, et al. Dominant and recessive inheritance of morbid obesity associated with melanocortin 4 receptor deficiency. J Clin Invest  2000; 106(2): 271-9.
 [http://dx.doi.org/10.1172/JCI9397 ] [PMID: 10903343]

[328]
Kobayashi H, Ogawa Y, Shintani M, et al. A Novel homozygous missense mutation of melanocortin-4 receptor (MC4R) in a Japanese woman with severe obesity. Diabetes  2002; 51(1): 243-6.
 [http://dx.doi.org/10.2337/diabetes.51.1.243 ] [PMID: 11756348]

[329]
Farooqi IS, Keogh JM, Yeo GSH, Lank EJ, Cheetham T, O’Rahilly S. Clinical spectrum of obesity and mutations in the melanocortin 4 receptor gene. N Engl J Med  2003; 348(12): 1085-95.
 [http://dx.doi.org/10.1056/NEJMoa022050 ] [PMID: 12646665]

[330]
Buono P, Pasanisi F, Nardelli C, et al. Six novel mutations in the proopiomelanocortin and melanocortin receptor 4 genes in severely obese adults living in southern Italy. Clin Chem  2005; 51(8): 1358-64.
 [http://dx.doi.org/10.1373/clinchem.2005.047886 ] [PMID: 15951321]

[331]
Dubern B, Bisbis S, Talbaoui H, et al. Homozygous null mutation of the melanocortin-4 receptor and severe early-onset obesity. J Pediatr  2007; 150(6): 613-7.
 [http://dx.doi.org/10.1016/j.jpeds.2007.01.041]

[332]
Martinelli CE, Keogh JM, Greenfield JR, et al. Obesity due to melanocortin 4 receptor (MC4R) deficiency is associated with increased linear growth and final height, fasting hyperinsulinemia, and incompletely suppressed growth hormone secretion. J Clin Endocrinol Metab  2011; 96(1): E181-8.
 [http://dx.doi.org/10.1210/jc.2010-1369 ] [PMID: 21047921]

[333]
Thearle MS, Muller YL, Hanson RL, et al. Greater impact of melanocortin-4 receptor deficiency on rates of growth and risk of type 2 diabetes during childhood compared with adulthood in Pima Indians. Diabetes  2012; 61(1): 250-7.
 [http://dx.doi.org/10.2337/db11-0708 ] [PMID: 22106157]

[334]
Vaisse C, Clement K, Durand E, Hercberg S, Guy-Grand B, Froguel P. Melanocortin-4 receptor mutations are a frequent and heterogeneous cause of morbid obesity. J Clin Invest  2000; 106(2): 253-62.
 [http://dx.doi.org/10.1172/JCI9238 ] [PMID: 10903341]

[335]
Lubrano-Berthelier C, Dubern B, Lacorte JM, et al. Melanocortin 4 receptor mutations in a large cohort of severely obese adults: Prevalence, functional classification, genotype-phenotype relationship, and lack of association with binge eating. J Clin Endocrinol Metab  2006; 91(5): 1811-8.
 [http://dx.doi.org/10.1210/jc.2005-1411 ] [PMID: 16507637]

[336]
Lubrano-Berthelier C, Le Stunff C, Bougnères P, Vaisse C. A homozygous null mutation delineates the role of the melanocortin-4 receptor in humans. J Clin Endocrinol Metab  2004; 89(5): 2028-32.
 [http://dx.doi.org/10.1210/jc.2003-031993 ] [PMID: 15126516]

[337]
Collet TH, Dubern B, Mokrosinski J, et al. Evaluation of a melanocortin-4 receptor (MC4R) agonist (Setmelanotide) in MC4R deficiency. Mol Metab  2017; 6(10): 1321-9.
 [http://dx.doi.org/10.1016/j.molmet.2017.06.015 ] [PMID: 29031731]

[338]
Fojas EGF, Radha SK, Ali T, Nadler EP, Lessan N. Weight and glycemic control outcomes of bariatric surgery and pharmacotherapy in patients with melanocortin-4 receptor deficiency. Front Endocrinol (Lausanne)  2022; 12: 792354.
 [http://dx.doi.org/10.3389/fendo.2021.792354 ] [PMID: 35095762]

[339]
Cooiman MI, Alsters SIM, Duquesnoy M, et al. Long-term weight outcome after bariatric surgery in patients with melanocortin-4 receptor gene variants: A Case–Control Study of 105 Patients. Obes Surg  2022; 32(3): 837-44.
 [http://dx.doi.org/10.1007/s11695-021-05869-x ] [PMID: 34984630]

[340]
Geller F, Reichwald K, Dempfle A, et al. Melanocortin-4 receptor gene variant I103 is negatively associated with obesity. Am J Hum Genet  2004; 74(3): 572-81.
 [http://dx.doi.org/10.1086/382490 ] [PMID: 14973783]

[341]
Stutzmann F, Vatin V, Cauchi S, et al. Non-synonymous polymorphisms in melanocortin-4 receptor protect against obesity: The two facets of a Janus obesity gene. Hum Mol Genet  2007; 16(15): 1837-44.
 [http://dx.doi.org/10.1093/hmg/ddm132 ] [PMID: 17519222]

[342]
Krude H, Biebermann H, Schnabel D, et al. Obesity due to proopiomelanocortin deficiency: Three new cases and treatment trials with thyroid hormone and ACTH4-10. J Clin Endocrinol Metab  2003; 88(10): 4633-40.
 [http://dx.doi.org/10.1210/jc.2003-030502 ] [PMID: 14557433]

[343]
Clément K, Dubern B, Mencarelli M, et al. Unexpected endocrine features and normal pigmentation in a young adult patient carrying a novel homozygous mutation in the POMC gene. J Clin Endocrinol Metab  2008; 93(12): 4955-62.
 [http://dx.doi.org/10.1210/jc.2008-1164 ] [PMID: 18765507]

[344]
Darcan S, Can S, Goksen D, Asar G. Transient salt wasting in POMC-deficiency due to infection induced stress. Exp Clin Endocrinol Diabetes  2010; 118(4): 281-3.
 [http://dx.doi.org/10.1055/s-0029-1241203 ] [PMID: 19998238]

[345]
Mendiratta MS, Yang Y, Balazs AE, et al. Early onset obesity and adrenal insufficiency associated with a homozygous POMC mutation. Int J Pediatr Endocrinol  2011; 2011(1): 5.
 [http://dx.doi.org/10.1186/1687-9856-2011-5 ] [PMID: 21860632]

[346]
Cirillo G, Marini R, Ito S, et al. Lack of red hair phenotype in a North‐African obese child homozygous for a novel POMC null mutation: Nonsense‐mediated decay RNA evaluation and hair pigment chemical analysis. Br J Dermatol  2012; 167(6): 1393-5.
 [http://dx.doi.org/10.1111/j.1365-2133.2012.11060.x ] [PMID: 22612534]

[347]
Hung CN, Poon WT, Lee CY, Law CY, Chan AYW. A case of early-onset obesity, hypocortisolism, and skin pigmentation problem due to a novel homozygous mutation in the proopiomelanocortin (POMC) gene in an Indian boy. J Pediatr Endocrinol Metab  2012; 25(1-2): 175-9.
 [http://dx.doi.org/10.1515/jpem-2011-0437 ] [PMID: 22570972]

[348]
Ozen S, Aldemir O. Early-onset severe obesity with ACTH deficiency and red hair in a boy: The POMC deficiency. Genet Couns  2012; 23(4): 493-5.
 [PMID: 23431750]

[349]
Aslan IR, Ranadive SA, Valle I, Kollipara S, Noble JA, Vaisse C. The melanocortin system and insulin resistance in humans: Insights from a patient with complete POMC deficiency and type 1 diabetes mellitus. Int J Obes  2014; 38(1): 148-51.
 [http://dx.doi.org/10.1038/ijo.2013.53 ] [PMID: 23649472]

[350]
Ozsu E, Bahm A. Delayed diagnosis of proopiomelanocortin (POMC) deficiency with type 1 diabetes in a 9-year-old girl and her infant sibling. J Pediatr Endocrinol Metab  2017; 30(10): 1137-40.
 [http://dx.doi.org/10.1515/jpem-2017-0064 ] [PMID: 28915118]

[351]
Hilado MA, Randhawa RS. A novel mutation in the proopiomelanocortin (POMC) gene of a Hispanic child: Metformin treatment shows a beneficial impact on the body mass index. J Pediatr Endocrinol Metab  2018; 31(7): 815-9.
 [http://dx.doi.org/10.1515/jpem-2017-0467 ] [PMID: 29858905]

[352]
Çetinkaya S, Güran T, Kurnaz E, et al. A Patient with Proopiomelanocortin Deficiency: An Increasingly Important Diagnosis to Make. J Clin Res Pediatr Endocrinol  2018; 10(1): 68-73.
 [http://dx.doi.org/10.4274/jcrpe.4638 ] [PMID: 28739551]

[353]
Graves LE, Khouri JM, Kristidis P, Verge CF. Proopiomelanocortin deficiency diagnosed in infancy in two boys and a review of the known cases. J Paediatr Child Health  2021; 57(4): 484-90.
 [http://dx.doi.org/10.1111/jpc.15407 ] [PMID: 33666293]

[354]
Gregoric N, Groselj U, Bratina N, et al. Two cases with an early presented proopiomelanocortin deficiency—A long-term follow-up and systematic literature review. front endocrinol (Lausanne)  2021; 12: 689387.
 [http://dx.doi.org/10.3389/fendo.2021.689387] [PMID: 34177811]

[355]
Farooqi IS, Drop S, Clements A, et al. Heterozygosity for a POMC-null mutation and increased obesity risk in humans. Diabetes  2006; 55(9): 2549-53.
 [http://dx.doi.org/10.2337/db06-0214 ] [PMID: 16936203]

[356]
Hearn T, Spalluto C, Phillips VJ, et al. Subcellular localization of ALMS1 supports involvement of centrosome and basal body dysfunction in the pathogenesis of obesity, insulin resistance, and type 2 diabetes. Diabetes  2005; 54(5): 1581-7.
 [http://dx.doi.org/10.2337/diabetes.54.5.1581 ] [PMID: 15855349]

[357]
Knorz VJ, Spalluto C, Lessard M, et al. Centriolar association of ALMS1 and likely centrosomal functions of the ALMS motif-containing proteins C10orf90 and KIAA1731. Mol Biol Cell  2010; 21(21): 3617-29.
 [http://dx.doi.org/10.1091/mbc.e10-03-0246 ] [PMID: 20844083]

[358]
Marshall JD, Maffei P, Collin GB, Naggert JK. Alström syndrome: Genetics and clinical overview. Curr Genomics  2011; 12(3): 225-35.
 [http://dx.doi.org/10.2174/138920211795677912 ] [PMID: 22043170]

[359]
Leitch CC, Lodh S, Prieto-Echagüe V, Badano JL, Zaghloul NA. Basal body proteins regulate Notch signaling via endosomal trafficking. J Cell Sci  2014; 127(Pt 11): jcs.130344.
 [http://dx.doi.org/10.1242/jcs.130344] [PMID: 24681783]

[360]
Marshall JD, Bronson RT, Collin GB, et al. New Alström syndrome phenotypes based on the evaluation of 182 cases. Arch Intern Med  2005; 165(6): 675-83.
 [http://dx.doi.org/10.1001/archinte.165.6.675 ] [PMID: 15795345]

[361]
Jatti K, Paisey R, More R. Coronary artery disease in Alström syndrome. Eur J Hum Genet  2012; 20(1): 117-8.
 [http://dx.doi.org/10.1038/ejhg.2011.168 ] [PMID: 21897446]

[362]
Han JC, Reyes-Capo DP, Liu CY, et al. Comprehensive endocrine-metabolic evaluation of patients with alström syndrome compared with BMI-matched controls. J Clin Endocrinol Metab  2018; 103(7): 2707-19.
 [http://dx.doi.org/10.1210/jc.2018-00496 ] [PMID: 29718281]

[363]
Satman I, Yılmaz Mt, Gürsoy N. et al.Evaluation of insulin resistant diabetes mellitus in Alström syndrome: A long-term prospective follow-up of three siblings. Diabetes Res Clin Pract  2002; 56(3): 189-96.
 [http://dx.doi.org/10.1016/S0168-8227(02)00004-9 ] [PMID: 11947966]

[364]
Minton JAL, Owen KR, Ricketts CJ, et al. Syndromic obesity and diabetes: Changes in body composition with age and mutation analysis of ALMS1 in 12 United Kingdom kindreds with Alstrom syndrome. J Clin Endocrinol Metab  2006; 91(8): 3110-6.
 [http://dx.doi.org/10.1210/jc.2005-2633 ] [PMID: 16720663]

[365]
Pirgon O, Atabek ME, Tanju IA. Metabolic syndrome features presenting in early childhood in Alström syndrome: A case report. J Clin Res Pediatr Endocrinol  2009; 1(6): 278-80.
 [http://dx.doi.org/10.4274/jcrpe.v1i6.278 ] [PMID: 21274310]

[366]
Romano S, Maffei P, Bettini V, et al. Alström syndrome is associated with short stature and reduced GH reserve. Clin Endocrinol (Oxf)  2013; 79(4): 529-36.
 [http://dx.doi.org/10.1111/cen.12180 ] [PMID: 23445176]

[367]
Paisey RB, Hodge D, Williams K. Body fat distribution, serum glucose, lipid and insulin response to meals in Alström syndrome. J Hum Nutr Diet  2008; 21(3): 268-74.
 [http://dx.doi.org/10.1111/j.1365-277X.2008.00866.x ] [PMID: 18477182]

[368]
Mokashi A, Cummings EA. Presentation and course of diabetes in children and adolescents with Alstrom syndrome. Pediatr Diabetes  2011; 12(3pt2): 270-5.
 [http://dx.doi.org/10.1111/j.1399-5448.2010.00698.x ] [PMID: 21518413]

[369]
Deveault C, Billingsley G, Duncan JL, et al. BBS genotype-phenotype assessment of a multiethnic patient cohort calls for a revision of the disease definition. Hum Mutat  2011; 32(6): 610-9.
 [http://dx.doi.org/10.1002/humu.21480 ] [PMID: 21344540]

[370]
Feuillan PP, Ng D, Han JC, et al. Patients with Bardet-Biedl syndrome have hyperleptinemia suggestive of leptin resistance. J Clin Endocrinol Metab  2011; 96(3): E528-35.
 [http://dx.doi.org/10.1210/jc.2010-2290 ] [PMID: 21209035]

[371]
Marion V, Stoetzel C, Schlicht D, et al. Transient ciliogenesis involving Bardet-Biedl syndrome proteins is a fundamental characteristic of adipogenic differentiation. Proc Natl Acad Sci USA  2009; 106(6): 1820-5.
 [http://dx.doi.org/10.1073/pnas.0812518106 ] [PMID: 19190184]

[372]
Marion V, Mockel A, De Melo C, et al. BBS-induced ciliary defect enhances adipogenesis, causing paradoxical higher-insulin sensitivity, glucose usage, and decreased inflammatory response. Cell Metab  2012; 16(3): 363-77.
 [http://dx.doi.org/10.1016/j.cmet.2012.08.005 ] [PMID: 22958920]

[373]
Green JS, Parfrey PS, Harnett JD, et al. The cardinal manifestations of Bardet-Biedl syndrome, a form of Laurence-Moon-Biedl syndrome. N Engl J Med  1989; 321(15): 1002-9.
 [http://dx.doi.org/10.1056/NEJM198910123211503 ] [PMID: 2779627]

[374]
Carmi R, Elbedour K, Stone EM, Sheffield VC. Phenotypic differences among patients with Bardet-Biedl syndrome linked to three different chromosome loci. Am J Med Genet  1995; 59(2): 199-203.
 [http://dx.doi.org/10.1002/ajmg.1320590216 ] [PMID: 8588586]

[375]
Beales PL, Elcioglu N, Woolf AS, Parker D, Flinter FA. New criteria for improved diagnosis of Bardet-Biedl syndrome: Results of a population survey. J Med Genet  1999; 36(6): 437-46.
 [http://dx.doi.org/10.1136/jmg.36.6.437 ] [PMID: 10874630]

[376]
Iannello S, Bosco P, Cavaleri A, Camuto M, Milazzo P, Belfiore F. A review of the literature of Bardet-Biedl disease and report of three cases associated with metabolic syndrome and diagnosed after the age of fifty. Obes Rev  2002; 3(2): 123-35.
 [http://dx.doi.org/10.1046/j.1467-789X.2002.00055.x ] [PMID: 12120419]

[377]
Keskin M, Atabek ME. Kurtoğlu S. Bardet-Biedl syndrome with syndrome X: A patient report. J Pediatr Endocrinol Metab  2004; 17(6): 913-5.
 [http://dx.doi.org/10.1515/JPEM.2004.17.6.914 ] [PMID: 15270411]

[378]
Benzinou M, Walley A, Lobbens S, et al. Bardet-Biedl syndrome gene variants are associated with both childhood and adult common obesity in French Caucasians. Diabetes  2006; 55(10): 2876-82.
 [http://dx.doi.org/10.2337/db06-0337 ] [PMID: 17003356]

[379]
Forsythe E, Beales PL. Bardet–Biedl syndrome. Eur J Hum Genet  2013; 21(1): 8-13.
 [http://dx.doi.org/10.1038/ejhg.2012.115 ] [PMID: 22713813]

[380]
Lim ET, Liu YP, Chan Y, et al. A novel test for recessive contributions to complex diseases implicates Bardet-Biedl syndrome gene BBS10 in idiopathic type 2 diabetes and obesity. Am J Hum Genet  2014; 95(5): 509-20.
 [http://dx.doi.org/10.1016/j.ajhg.2014.09.015 ] [PMID: 25439097]

[381]
Jeziorny K, Antosik K, Jakiel P. Młynarski W, Borowiec M, Zmysłowska A. Next-Generation Sequencing in the Diagnosis of Patients with Bardet–Biedl Syndrome—New Variants and Relationship with Hyperglycemia and Insulin Resistance. Genes (Basel)  2020; 11(11): 1283.
 [http://dx.doi.org/10.3390/genes11111283 ] [PMID: 33138063]

[382]
Sherafat-Kazemzadeh R, Ivey L, Kahn SR, et al. Hyperphagia among patients with Bardet-Biedl syndrome. Pediatr Obes  2013; 8(5): e64-7.
 [http://dx.doi.org/10.1111/j.2047-6310.2013.00182.x ] [PMID: 23776152]

[383]
Mujahid S, Hunt KF, Cheah YS, et al. The endocrine and metabolic characteristics of a Large Bardet-biedl syndrome clinic population. J Clin Endocrinol Metab  2018; 103(5): 1834-41.
 [http://dx.doi.org/10.1210/jc.2017-01459 ] [PMID: 29409041]

[384]
Grace C, Beales P, Summerbell C, et al. Energy metabolism in Bardet–Biedl syndrome. Int J Obes  2003; 27(11): 1319-24.
 [http://dx.doi.org/10.1038/sj.ijo.0802420 ] [PMID: 14574341]

[385]
Moore SJ, Green JS, Fan Y, et al. Clinical and genetic epidemiology of Bardet-Biedl syndrome in Newfoundland: A 22-year prospective, population-based, cohort study. Am J Med Genet A  2005; 132A(4): 352-60.
 [http://dx.doi.org/10.1002/ajmg.a.30406 ] [PMID: 15637713]

[386]
Webb MP, Dicks EL, Green JS, et al. Autosomal recessive Bardet–Biedl syndrome: First-degree relatives have no predisposition to metabolic and renal disorders. Kidney Int  2009; 76(2): 215-23.
 [http://dx.doi.org/10.1038/ki.2009.116 ] [PMID: 19367329]

[387]
Imhoff O, Marion V, Stoetzel C, et al. Bardet-Biedl Syndrome. Clin J Am Soc Nephrol  2011; 6(1): 22-9.
 [http://dx.doi.org/10.2215/CJN.03320410 ] [PMID: 20876674]

[388]
Rouskas K, Paletas K, Kalogeridis A, et al. Association between BBS6/MKKS gene polymorphisms, obesity and metabolic syndrome in the Greek population. Int J Obes  2008; 32(11): 1618-25.
 [http://dx.doi.org/10.1038/ijo.2008.167 ] [PMID: 18813213]

[389]
Hendricks AE, Bochukova EG, Marenne G, et al. Rare Variant Analysis of Human and Rodent Obesity Genes in Individuals with Severe Childhood Obesity. Sci Rep  2017; 7(1): 4394.
 [http://dx.doi.org/10.1038/s41598-017-03054-8 ] [PMID: 28663568]
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