Login Register Cart 0
Generic placeholder image

Current Diabetes Reviews

Editor-in-Chief

ISSN (Print): 1573-3998
ISSN (Online): 1875-6417

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

Is “Leptin Resistance” Another Key Resistance to Manage Type 2 Diabetes?

Author(s): Juan Salazar*, Mervin Chávez-Castillo, Joselyn Rojas, Angel Ortega, Manuel Nava, José Pérez, Milagros Rojas, Cristobal Espinoza, Maricarmen Chacin, Yaneth Herazo, Lissé Angarita, Diana Marcela Rojas, Luis D’Marco and Valmore Bermudez

Volume 16, Issue 7, 2020

Page: [733 - 749] Pages: 17

DOI: 10.2174/1573399816666191230111838

Price: $65

Abstract

Although novel pharmacological options for the treatment of type 2 diabetes mellitus (DM2) have been observed to modulate the functionality of several key organs in glucose homeostasis, successful regulation of insulin resistance (IR), body weight management, and pharmacological treatment of obesity remain notable problems in endocrinology. Leptin may be a pivotal player in this scenario, as an adipokine which centrally regulates appetite and energy balance. In obesity, excessive caloric intake promotes a low-grade inflammatory response, which leads to dysregulations in lipid storage and adipokine secretion. In turn, these entail alterations in leptin sensitivity, leptin transport across the blood-brain barrier and defects in post-receptor signaling. Furthermore, hypothalamic inflammation and endoplasmic reticulum stress may increase the expression of molecules which may disrupt leptin signaling. Abundant evidence has linked obesity and leptin resistance, which may precede or occur simultaneously to IR and DM2. Thus, leptin sensitivity may be a potential early therapeutic target that demands further preclinical and clinical research. Modulators of insulin sensitivity have been tested in animal models and small clinical trials with promising results, especially in combination with agents such as amylin and GLP-1 analogs, in particular, due to their central activity in the hypothalamus.

Keywords: Leptin, leptin resistance, diabetes, obesity, hyperleptinemia, insulin resistance, adipokines.

[1]
IDF Diabetes Atlas 9th, 2019 Available:. https: //www.diabetesatlas.org/en/
[2]
Stevens GA, Singh GM, Lu Y, et al. Global Burden of Metabolic Risk Factors of Chronic Diseases Collaborating Group (Body Mass Index). National, regional, and global trends in adult overweight and obesity prevalences Popul Health Metr. 2012; 10(1): 22.
[http://dx.doi.org/10.1186/1478-7954-10-22] [PMID: 23167948]
[3]
Imam K. Clinical features, diagnostic criteria and pathogenesis of diabetes mellitus. Adv Exp Med Biol 2012; 771: 340-55.
[http://dx.doi.org/10.1007/978-1-4614-5441-0_25] [PMID: 23393689]
[4]
Münzberg H. Leptin-signaling pathways and leptin resistance. Forum Nutr 2010; 63: 123-32.
[http://dx.doi.org/10.1159/000264400] [PMID: 19955780]
[5]
Morales Clavijo M, Carvajal Garcés CF. Obesidad y resistencia a la leptina. Gac Méd Boliv 2010; 33: 63-8.
[6]
Münzberg H, Morrison CD. Structure, production and signaling of leptin. Metabolism 2015; 64(1): 13-23.
[http://dx.doi.org/10.1016/j.metabol.2014.09.010] [PMID: 25305050]
[7]
Dardeno TA, Chou SH, Moon HS, Chamberland JP, Fiorenza CG, Mantzoros CS. Leptin in human physiology and therapeutics. Front Neuroendocrinol 2010; 31(3): 377-93.
[http://dx.doi.org/10.1016/j.yfrne.2010.06.002] [PMID: 20600241]
[8]
Ribeiro L, Busnello JV, Licínio J. Pulsatile and Diurnal Leptin Rhythms. Leptin 2006; 25: 247-62.
[http://dx.doi.org/10.1007/978-0-387-31416-7_13]
[9]
Villanueva EC, Myers MG Jr. Leptin receptor signaling and the regulation of mammalian physiology. Int J Obes 2008; 32(Suppl. 7): S8-S12.
[http://dx.doi.org/10.1038/ijo.2008.232] [PMID: 19136996]
[10]
Leinninger GM, Myers MG Jr. LRb signals act within a distributed network of leptin-responsive neurones to mediate leptin action. Acta Physiol (Oxf) 2008; 192(1): 49-59.
[http://dx.doi.org/10.1111/j.1748-1716.2007.01784.x] [PMID: 18171429]
[11]
Wang P, Yang FJ, Du H, et al. Involvement of leptin receptor long isoform (LepRb)-STAT3 signaling pathway in brain fat mass- and obesity-associated (FTO) downregulation during energy restriction. Mol Med 2011; 17(5-6): 523-32.
[http://dx.doi.org/10.2119/molmed.2010.000134] [PMID: 21267512]
[12]
Dalamaga M, Chou SH, Shields K, Papageorgiou P, Polyzos SA, Mantzoros CS. Leptin at the intersection of neuroendocrinology and metabolism: current evidence and therapeutic perspectives. Cell Metab 2013; 18(1): 29-42.
[http://dx.doi.org/10.1016/j.cmet.2013.05.010] [PMID: 23770129]
[13]
Myers MG, Cowley MA, Münzberg H. Mechanisms of leptin action and leptin resistance. Annu Rev Physiol 2008; 70: 537-56.
[http://dx.doi.org/10.1146/annurev.physiol.70.113006.100707] [PMID: 17937601]
[14]
Zabolotny JM, Bence-Hanulec KK, Stricker-Krongrad A, et al. PTP1B regulates leptin signal transduction in vivo. Dev Cell 2002; 2(4): 489-95.
[http://dx.doi.org/10.1016/S1534-5807(02)00148-X] [PMID: 11970898]
[15]
Klok MD, Jakobsdottir S, Drent ML. The role of leptin and ghrelin in the regulation of food intake and body weight in humans: a review. Obes Rev 2007; 8(1): 21-34.
[http://dx.doi.org/10.1111/j.1467-789X.2006.00270.x] [PMID: 17212793]
[16]
Pandit R, Beerens S, Adan RAH. Role of leptin in energy expenditure: the hypothalamic perspective. Am J Physiol Regul Integr Comp Physiol 2017; 312(6): R938-47.
[http://dx.doi.org/10.1152/ajpregu.00045.2016] [PMID: 28356295]
[17]
Timper K, Brüning JC. Hypothalamic circuits regulating appetite and energy homeostasis: pathways to obesity. Dis Model Mech 2017; 10(6): 679-89.
[http://dx.doi.org/10.1242/dmm.026609] [PMID: 28592656]
[18]
Myers MG Jr, Münzberg H, Leinninger GM, Leshan RL. The geometry of leptin action in the brain: more complicated than a simple ARC. Cell Metab 2009; 9(2): 117-23.
[http://dx.doi.org/10.1016/j.cmet.2008.12.001] [PMID: 19187770]
[19]
Banks AS, Davis SM, Bates SH, Myers MG Jr. Activation of downstream signals by the long form of the leptin receptor. J Biol Chem 2000; 275(19): 14563-72.
[http://dx.doi.org/10.1074/jbc.275.19.14563] [PMID: 10799542]
[20]
Münzberg H, Flier JS, Bjørbaek C. Region-specific leptin resistance within the hypothalamus of diet-induced obese mice. Endocrinology 2004; 145(11): 4880-9.
[http://dx.doi.org/10.1210/en.2004-0726] [PMID: 15271881]
[21]
Marsh DJ, Hollopeter G, Huszar D, et al. Response of melanocortin-4 receptor-deficient mice to anorectic and orexigenic peptides. Nat Genet 1999; 21(1): 119-22.
[http://dx.doi.org/10.1038/5070] [PMID: 9916804]
[22]
Elmquist JK, Coppari R, Balthasar N, Ichinose M, Lowell BB. Identifying hypothalamic pathways controlling food intake, body weight, and glucose homeostasis. J Comp Neurol 2005; 493(1): 63-71.
[http://dx.doi.org/10.1002/cne.20786] [PMID: 16254991]
[23]
Ramos-Lobo AM, Donato J Jr. The role of leptin in health and disease. Temperature (Austin) 2017; 4(3): 258-91.
[http://dx.doi.org/10.1080/23328940.2017.1327003] [PMID: 28944270]
[24]
Caputo T, Gilardi F, Desvergne B. From chronic overnutrition to metaflammation and insulin resistance: adipose tissue and liver contributions. FEBS Lett 2017; 591(19): 3061-88.
[http://dx.doi.org/10.1002/1873-3468.12742] [PMID: 28677122]
[25]
Muir LA, Neeley CK, Meyer KA, et al. Adipose tissue fibrosis, hypertrophy, and hyperplasia: Correlations with diabetes in human obesity. Obesity (Silver Spring) 2016; 24(3): 597-605.
[http://dx.doi.org/10.1002/oby.21377] [PMID: 26916240]
[26]
Trayhurn P. Hypoxia and adipose tissue function and dysfunction in obesity. Physiol Rev 2013; 93(1): 1-21.
[http://dx.doi.org/10.1152/physrev.00017.2012] [PMID: 23303904]
[27]
Knight ZA, Hannan KS, Greenberg ML, Friedman JM. Hyperleptinemia is required for the development of leptin resistance. PLoS One 2010; 5(6) e11376
[http://dx.doi.org/10.1371/journal.pone.0011376] [PMID: 20613882]
[28]
Leon-Cabrera S, Solís-Lozano L, Suárez-Álvarez K, et al. Hyperleptinemia is associated with parameters of low-grade systemic inflammation and metabolic dysfunction in obese human beings. Front Integr Nuerosci 2013; 7: 62.
[http://dx.doi.org/10.3389/fnint.2013.00062] [PMID: 23986664]
[29]
Bermúdez V, Rojas J, Aguirre M, Cano C, Arraiz N, Silva-Paredes C, et al. 2011.http://www.intechopen.com/books/role-of-the-adipocyte-indevelopment-of-type-2-diabetes/the-sick-adipocyte-theory-the-forces-of-clustering-at-glance
[30]
Stanford KI, Goodyear LJ. Muscle-Adipose Tissue Cross Talk. Cold Spring Harb Perspect Med 2018; 8(8) a029801
[http://dx.doi.org/10.1101/cshperspect.a029801] [PMID: 28507197]
[31]
Yadav A, Kataria MA, Saini V, Yadav A. Role of leptin and adiponectin in insulin resistance. Clin Chim Acta 2013; 417: 80-4.
[http://dx.doi.org/10.1016/j.cca.2012.12.007] [PMID: 23266767]
[32]
Blüher M, Mantzoros CS. From leptin to other adipokines in health and disease: facts and expectations at the beginning of the 21st century. Metabolism 2015; 64(1): 131-45.
[http://dx.doi.org/10.1016/j.metabol.2014.10.016] [PMID: 25497344]
[33]
Frühbeck G, Catalán V, Rodríguez A, et al. Involvement of the leptin-adiponectin axis in inflammation and oxidative stress in the metabolic syndrome. Sci Rep 2017; 7(1): 6619.
[http://dx.doi.org/10.1038/s41598-017-06997-0] [PMID: 28747790]
[34]
Frühbeck G, Catalán V, Rodríguez A, Gómez-Ambrosi J. Adiponectin-leptin ratio: A promising index to estimate adipose tissue dysfunction. Relation with obesity-associated cardiometabolic risk. Adipocyte 2018; 7(1): 57-62.
[http://dx.doi.org/10.1080/21623945.2017.1402151] [PMID: 29205099]
[35]
Banks WA, Farr SA, Salameh TS, et al. Triglycerides cross the blood-brain barrier and induce central leptin and insulin receptor resistance. Int J Obes 2018; 42(3): 391-7.
[http://dx.doi.org/10.1038/ijo.2017.231] [PMID: 28990588]
[36]
Morris DL, Rui L. Recent advances in understanding leptin signaling and leptin resistance. Am J Physiol Endocrinol Metab 2009; 297(6): E1247-59.
[http://dx.doi.org/10.1152/ajpendo.00274.2009] [PMID: 19724019]
[37]
Banks WA, DiPalma CR, Farrell CL. Impaired transport of leptin across the blood-brain barrier in obesity. Peptides 1999; 20(11): 1341-5.
[http://dx.doi.org/10.1016/S0196-9781(99)00139-4] [PMID: 10612449]
[38]
van de Sande-Lee S, Cardoso AR, Garlipp CR, et al. Cerebrospinal fluid xenin levels during body mass reduction: no evidence for obesity-associated defective transport across the blood-brain barrier. Int J Obes 2013; 37(3): 416-9.
[http://dx.doi.org/10.1038/ijo.2012.70] [PMID: 22546776]
[39]
El-Haschimi K, Pierroz DD, Hileman SM, Bjørbaek C, Flier JS. Two defects contribute to hypothalamic leptin resistance in mice with diet-induced obesity. J Clin Invest 2000; 105(12): 1827-32.
[http://dx.doi.org/10.1172/JCI9842] [PMID: 10862798]
[40]
Li J, Wei D, McCrory MA, et al. Human C-reactive protein impedes entry of leptin into the CNS and attenuates its physiological actions in the CNS. Biochem J 2016; 473(9): 1215-24.
[http://dx.doi.org/10.1042/BJ20151282] [PMID: 26933237]
[41]
Cui H, López M, Rahmouni K. The cellular and molecular bases of leptin and ghrelin resistance in obesity. Nat Rev Endocrinol 2017; 13(6): 338-51.
[http://dx.doi.org/10.1038/nrendo.2016.222] [PMID: 28232667]
[42]
Ren D, Li M, Duan C, Rui L. Identification of SH2-B as a key regulator of leptin sensitivity, energy balance, and body weight in mice. Cell Metab 2005; 2(2): 95-104.
[http://dx.doi.org/10.1016/j.cmet.2005.07.004] [PMID: 16098827]
[43]
Li Z, Zhou Y, Carter-Su C, Myers MG Jr, Rui L. SH2B1 enhances leptin signaling by both Janus kinase 2 Tyr813 phosphorylation-dependent and -independent mechanisms. Mol Endocrinol 2007; 21(9): 2270-81.
[http://dx.doi.org/10.1210/me.2007-0111] [PMID: 17565041]
[44]
Duan C, Li M, Rui L. SH2-B promotes insulin receptor substrate 1 (IRS1)- and IRS2-mediated activation of the phosphatidylinositol 3-kinase pathway in response to leptin. J Biol Chem 2004; 279(42): 43684-91.
[http://dx.doi.org/10.1074/jbc.M408495200] [PMID: 15316008]
[45]
Zhou Y, Rui L. Leptin signaling and leptin resistance. Front Med 2013; 7(2): 207-22.
[http://dx.doi.org/10.1007/s11684-013-0263-5] [PMID: 23580174]
[46]
Bjørbaek C, El-Haschimi K, Frantz JD, Flier JS. The role of SOCS-3 in leptin signaling and leptin resistance. J Biol Chem 1999; 274(42): 30059-65.
[http://dx.doi.org/10.1074/jbc.274.42.30059] [PMID: 10514492]
[47]
Kaszubska W, Falls HD, Schaefer VG, et al. Protein tyrosine phosphatase 1B negatively regulates leptin signaling in a hypothalamic cell line. Mol Cell Endocrinol 2002; 195(1-2): 109-18.
[http://dx.doi.org/10.1016/S0303-7207(02)00178-8] [PMID: 12354677]
[48]
Bjorbak C, Lavery HJ, Bates SH, et al. SOCS3 mediates feedback inhibition of the leptin receptor via Tyr985. J Biol Chem 2000; 275(51): 40649-57.
[http://dx.doi.org/10.1074/jbc.M007577200] [PMID: 11018044]
[49]
Lund IK, Hansen JA, Andersen HS, Møller NP, Billestrup N. Mechanism of protein tyrosine phosphatase 1B-mediated inhibition of leptin signalling. J Mol Endocrinol 2005; 34(2): 339-51.
[http://dx.doi.org/10.1677/jme.1.01694] [PMID: 15821101]
[50]
Howard JK, Cave BJ, Oksanen LJ, Tzameli I, Bjørbaek C, Flier JS. Enhanced leptin sensitivity and attenuation of diet-induced obesity in mice with haploinsufficiency of Socs3. Nat Med 2004; 10(7): 734-8.
[http://dx.doi.org/10.1038/nm1072] [PMID: 15220914]
[51]
Tsou RC, Zimmer DJ, De Jonghe BC, Bence KK. Deficiency of PTP1B in leptin receptor-expressing neurons leads to decreased body weight and adiposity in mice. Endocrinology 2012; 153(9): 4227-37.
[http://dx.doi.org/10.1210/en.2012-1548] [PMID: 22802463]
[52]
Thaler JP, Yi CX, Schur EA, et al. Obesity is associated with hypothalamic injury in rodents and humans. J Clin Invest 2012; 122(1): 153-62.
[http://dx.doi.org/10.1172/JCI59660] [PMID: 22201683]
[53]
Kwon O, Kim KW, Kim MS. Leptin signalling pathways in hypothalamic neurons. Cell Mol Life Sci 2016; 73(7): 1457-77.
[http://dx.doi.org/10.1007/s00018-016-2133-1] [PMID: 26786898]
[54]
Milanski M, Degasperi G, Coope A, et al. Saturated fatty acids produce an inflammatory response predominantly through the activation of TLR4 signaling in hypothalamus: implications for the pathogenesis of obesity. J Neurosci 2009; 29(2): 359-70.
[http://dx.doi.org/10.1523/JNEUROSCI.2760-08.2009] [PMID: 19144836]
[55]
Zhang X, Zhang G, Zhang H, Karin M, Bai H, Cai D. Hypothalamic IKKbeta/NF-kappaB and ER stress link overnutrition to energy imbalance and obesity. Cell 2008; 135(1): 61-73.
[http://dx.doi.org/10.1016/j.cell.2008.07.043] [PMID: 18854155]
[56]
Shi X, Wang X, Li Q, et al. Nuclear factor κB (NF-κB) suppresses food intake and energy expenditure in mice by directly activating the Pomc promoter. Diabetologia 2013; 56(4): 925-36.
[http://dx.doi.org/10.1007/s00125-013-2831-2] [PMID: 23370526]
[57]
Kleinridders A, Schenten D, Könner AC, et al. MyD88 signaling in the CNS is required for development of fatty acid-induced leptin resistance and diet-induced obesity. Cell Metab 2009; 10(4): 249-59.
[http://dx.doi.org/10.1016/j.cmet.2009.08.013] [PMID: 19808018]
[58]
Hotamisligil GS. Endoplasmic reticulum stress and the inflammatory basis of metabolic disease. Cell 2010; 140(6): 900-17.
[http://dx.doi.org/10.1016/j.cell.2010.02.034] [PMID: 20303879]
[59]
Cao SS, Luo KL, Shi L. Endoplasmic Reticulum Stress Interacts With Inflammation in Human Diseases. J Cell Physiol 2016; 231(2): 288-94.
[http://dx.doi.org/10.1002/jcp.25098] [PMID: 26201832]
[60]
Ozcan L, Ergin AS, Lu A, et al. Endoplasmic reticulum stress plays a central role in development of leptin resistance. Cell Metab 2009; 9(1): 35-51.
[http://dx.doi.org/10.1016/j.cmet.2008.12.004] [PMID: 19117545]
[61]
Williams KW, Liu T, Kong X, et al. Xbp1s in Pomc neurons connects ER stress with energy balance and glucose homeostasis. Cell Metab 2014; 20(3): 471-82.
[http://dx.doi.org/10.1016/j.cmet.2014.06.002] [PMID: 25017942]
[62]
Ropelle ER, Flores MB, Cintra DE, et al. IL-6 and IL-10 anti-inflammatory activity links exercise to hypothalamic insulin and leptin sensitivity through IKKbeta and ER stress inhibition. PLoS Biol 2010; 8(8) e1000465
[http://dx.doi.org/10.1371/journal.pbio.1000465] [PMID: 20808781]
[63]
Mazor R, Friedmann-Morvinski D, Alsaigh T, et al. Cleavage of the leptin receptor by matrix metalloproteinase-2 promotes leptin resistance and obesity in mice. Sci Transl Med 2018; 10(455) eaah6324
[http://dx.doi.org/10.1126/scitranslmed.aah6324] [PMID: 30135249]
[64]
Guo DF, Cui H, Zhang Q, et al. The BBSome controls energy homeostasis by mediating the transport of the leptin receptor to the plasma membrane. PLoS Genet 2016; 12(2) e1005890
[http://dx.doi.org/10.1371/journal.pgen.1005890] [PMID: 26926121]
[65]
López M. Hypothalamic Leptin Resistance: From BBB to BBSome. PLoS Genet 2016; 12(5) e1005980
[http://dx.doi.org/10.1371/journal.pgen.1005980] [PMID: 27149508]
[66]
Meek TH, Morton GJ. Leptin, diabetes, and the brain. Indian J Endocrinol Metab 2012; 16(Suppl. 3): S534-42.
[http://dx.doi.org/10.4103/2230-8210.105568] [PMID: 23565487]
[67]
Dubuc PU. The development of obesity, hyperinsulinemia, and hyperglycemia in ob/ob mice. Metabolism 1976; 25(12): 1567-74.
[68]
Zanchi D, Depoorter A, Egloff L, et al. The impact of gut hormones on the neural circuit of appetite and satiety: A systematic review. Neurosci Biobehav Rev 2017; 80: 457-75.
[http://dx.doi.org/10.1016/j.neubiorev.2017.06.013] [PMID: 28669754]
[69]
Qiu J, Wagner EJ, Rønnekleiv OK, Kelly MJ. Insulin and leptin excite anorexigenic pro-opiomelanocortin neurones via activation of TRPC5 channels. J Neuroendocrinol 2018; 30(2) e12501
[http://dx.doi.org/10.1111/jne.12501] [PMID: 28675783]
[70]
Marroquí L, Gonzalez A, Ñeco P, et al. Role of leptin in the pancreatic β-cell: effects and signaling pathways. J Mol Endocrinol 2012; 49(1): R9-R17.
[http://dx.doi.org/10.1530/JME-12-0025] [PMID: 22448029]
[71]
D’souza AM, Neumann UH, Glavas MM, Kieffer TJ. The glucoregulatory actions of leptin. Mol Metab 2017; 6(9): 1052-65.
[http://dx.doi.org/10.1016/j.molmet.2017.04.011] [PMID: 28951828]
[72]
Balland E, Chen W, Dodd GT, et al. Leptin Signaling in the Arcuate Nucleus Reduces Insulin’s Capacity to Suppress Hepatic Glucose Production in Obese Mice. Cell Rep 2019; 26(2): 346-355.e3.
[http://dx.doi.org/10.1016/j.celrep.2018.12.061] [PMID: 30625317]
[73]
St-Pierre J, Tremblay ML. Modulation of leptin resistance by protein tyrosine phosphatases. Cell Metab 2012; 15(3): 292-7.
[http://dx.doi.org/10.1016/j.cmet.2012.02.004] [PMID: 22405067]
[74]
Hussain Z, Khan JA. Food intake regulation by leptin: Mechanisms mediating gluconeogenesis and energy expenditure. Asian Pac J Trop Med 2017; 10(10): 940-4.
[http://dx.doi.org/10.1016/j.apjtm.2017.09.003] [PMID: 29111188]
[75]
Tudurí E, Marroquí L, Soriano S, et al. Inhibitory effects of leptin on pancreatic alpha-cell function. Diabetes 2009; 58(7): 1616-24.
[http://dx.doi.org/10.2337/db08-1787] [PMID: 19401420]
[76]
Sáinz N, Barrenetxe J, Moreno-Aliaga MJ, Martínez JA. Leptin resistance and diet-induced obesity: central and peripheral actions of leptin. Metabolism 2015; 64(1): 35-46.
[http://dx.doi.org/10.1016/j.metabol.2014.10.015] [PMID: 25497342]
[77]
Perry RJ, Petersen KF, Shulman GI. Pleotropic effects of leptin to reverse insulin resistance and diabetic ketoacidosis. Diabetologia 2016; 59(5): 933-7.
[http://dx.doi.org/10.1007/s00125-016-3909-4] [PMID: 26961503]
[78]
Nozhenko Y, Rodríguez AM, Palou A. Leptin rapidly induces the expression of metabolic and myokine genes in C2C12 muscle cells to regulate nutrient partition and oxidation. Cell Physiol Biochem 2015; 35(1): 92-103.
[http://dx.doi.org/10.1159/000369678] [PMID: 25547246]
[79]
Stark R, Ashley SE, Andrews ZB. AMPK and the neuroendocrine regulation of appetite and energy expenditure. Mol Cell Endocrinol 2013; 366(2): 215-23.
[http://dx.doi.org/10.1016/j.mce.2012.06.012] [PMID: 22789749]
[80]
Stern JH, Rutkowski JM, Scherer PE. Adiponectin, Leptin, and Fatty Acids in the Maintenance of Metabolic Homeostasis through Adipose Tissue Crosstalk. Cell Metab 2016; 23(5): 770-84.
[http://dx.doi.org/10.1016/0026-0495(76)90109-8] [PMID: 994838]
[81]
Klaman LD, Boss O, Peroni OD, et al. Increased energy expenditure, decreased adiposity, and tissue-specific insulin sensitivity in protein-tyrosine phosphatase 1B-deficient mice. Mol Cell Biol 2000; 20(15): 5479-89.
[http://dx.doi.org/10.1128/MCB.20.15.5479-5489.2000] [PMID: 10891488]
[82]
Pedroso JA, Buonfiglio DC, Cardinali LI, et al. Inactivation of SOCS3 in leptin receptor-expressing cells protects mice from diet-induced insulin resistance but does not prevent obesity. Mol Metab 2014; 3(6): 608-18.
[http://dx.doi.org/10.1016/j.molmet.2014.06.001] [PMID: 25161884]
[83]
Liang L, Chen J, Zhan L, et al. Endoplasmic reticulum stress impairs insulin receptor signaling in the brains of obese rats. PLoS One 2015; 10(5) e0126384
[http://dx.doi.org/10.1371/journal.pone.0126384] [PMID: 25978724]
[84]
Benomar Y, Roy AF, Aubourg A, Djiane J, Taouis M. Cross down-regulation of leptin and insulin receptor expression and signalling in a human neuronal cell line. Biochem J 2005; 388(Pt 3): 929-39.
[http://dx.doi.org/10.1042/BJ20041621] [PMID: 15715521]
[85]
Xu AW, Kaelin CB, Takeda K, Akira S, Schwartz MW, Barsh GS. PI3K integrates the action of insulin and leptin on hypothalamic neurons. J Clin Invest 2005; 115(4): 951-8.
[http://dx.doi.org/10.1172/JCI24301] [PMID: 15761497]
[86]
Plum L, Lin HV, Dutia R, et al. The obesity susceptibility gene Cpe links FoxO1 signaling in hypothalamic pro-opiomelanocortin neurons with regulation of food intake. Nat Med 2009; 15(10): 1195-201.
[http://dx.doi.org/10.1038/nm.2026] [PMID: 19767734]
[87]
Thon M, Hosoi T, Ozawa K. Possible Integrative Actions of Leptin and Insulin Signaling in the Hypothalamus Targeting Energy Homeostasis. Front Endocrinol (Lausanne) 2016; 7: 138.
[http://dx.doi.org/10.3389/fendo.2016.00138] [PMID: 27812350]
[88]
Donato J. The PI3K signaling pathway mediates the biological effects of leptin Arq Bras Endocrinol Metab 2010; 54(7): 591-591-602.
[89]
do Carmo J, da Silva A, Wang Z, Freeman N, Alsheik A, Adi A, et al. Regulation of blood pressure, appetite and glucose by leptin after inactivation of insulin receptor substrate 2 (IRS2) signaling in the entire brain or in POMC neurons. Hypertension 2016; 67(2): 378-86.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.115.06153] [PMID: 26628674]
[90]
Jung UJ, Choi MS. Obesity and its metabolic complications: the role of adipokines and the relationship between obesity, inflammation, insulin resistance, dyslipidemia and nonalcoholic fatty liver disease. Int J Mol Sci 2014; 15(4): 6184-223.
[http://dx.doi.org/10.3390/ijms15046184] [PMID: 24733068]
[91]
Fuster JJ, Ouchi N, Gokce N, Walsh K. Obesity-Induced Changes in Adipose Tissue Microenvironment and Their Impact on Cardiovascular Disease. Circ Res 2016; 118(11): 1786-807.
[http://dx.doi.org/10.1161/CIRCRESAHA.115.306885] [PMID: 27230642]
[92]
Yamashita A, Soga Y, Iwamoto Y, et al. Macrophage-adipocyte interaction: marked interleukin-6 production by lipopolysaccharide. Obesity (Silver Spring) 2007; 15(11): 2549-52.
[http://dx.doi.org/10.1038/oby.2007.305] [PMID: 18070744]
[93]
Paz-Filho G, Mastronardi C, Franco CB, Wang KB, Wong ML, Licinio J. Leptin: molecular mechanisms, systemic pro-inflammatory effects, and clinical implications. Arq Bras Endocrinol Metabol 2012; 56(9): 597-607.
[http://dx.doi.org/10.1590/S0004-27302012000900001] [PMID: 23329181]
[94]
Boden G. Free fatty acids, insulin resistance, and type 2 diabetes mellitus. Proc Assoc Am Physicians 1999; 111(3): 241-8.
[http://dx.doi.org/10.1046/j.1525-1381.1999.99220.x] [PMID: 10354364]
[95]
Nguyen MT, Satoh H, Favelyukis S, et al. JNK and tumor necrosis factor-alpha mediate free fatty acid-induced insulin resistance in 3T3-L1 adipocytes. J Biol Chem 2005; 280(42): 35361-71.
[http://dx.doi.org/10.1074/jbc.M504611200] [PMID: 16085647]
[96]
Lee JY, Ye J, Gao Z, et al. Reciprocal modulation of Toll-like receptor-4 signaling pathways involving MyD88 and phosphatidylinositol 3-kinase/AKT by saturated and polyunsaturated fatty acids. J Biol Chem 2003; 278(39): 37041-51.
[http://dx.doi.org/10.1074/jbc.M305213200] [PMID: 12865424]
[97]
Pietsch J, Batra A, Stroh T, et al. Toll-like receptor expression and response to specific stimulation in adipocytes and preadipocytes: on the role of fat in inflammation. Ann N Y Acad Sci 2006; 1072: 407-9.
[http://dx.doi.org/10.1196/annals.1326.021] [PMID: 17057223]
[98]
Lee JY, Hwang DH. The modulation of inflammatory gene expression by lipids: mediation through Toll-like receptors. Mol Cells 2006; 21(2): 174-85.
[http://dx.doi.org/10.1007/s10059-013-3068-0] [PMID: 16682810]
[99]
Rojas J, Bermúdez V, Leal E, Cano R, Luti Y, Acosta L, et al. Insulinorresistencia e hiperinsulinemia como factores de riesgo para enfermedad cardiovascular. Arch Venez Farmacol Ter 2010; 2: 53-64.
[100]
Zauner A, Nimmerrichter P, Anderwald C, et al. Severity of insulin resistance in critically ill medical patients. Metabolism 2007; 56(1): 1-5.
[http://dx.doi.org/10.1016/j.metabol.2006.08.014] [PMID: 17161218]
[101]
Xiang AH, Wang C, Peters RK, Trigo E, Kjos SL, Buchanan TA. Coordinate changes in plasma glucose and pancreatic beta-cell function in Latino women at high risk for type 2 diabetes. Diabetes 2006; 55(4): 1074-9.
[http://dx.doi.org/10.2337/diabetes.55.04.06.db05-1109] [PMID: 16567531]
[102]
Boden G. Free fatty acids (FFA), a link between obesity and insulin resistance. Front Biosci 1998; 3: d169-75.
[http://dx.doi.org/10.2741/A272] [PMID: 9450985]
[103]
Bays H, Mandarino L, DeFronzo RA. Role of the adipocyte, free fatty acids, and ectopic fat in pathogenesis of type 2 diabetes mellitus: peroxisomal proliferator-activated receptor agonists provide a rational therapeutic approach. J Clin Endocrinol Metab 2004; 89(2): 463-78.
[http://dx.doi.org/10.1210/jc.2003-030723] [PMID: 14764748]
[104]
Joffe BI, Panz VR, Raal FJ. From lipodystrophy syndromes to diabetes mellitus. Lancet 2001; 357(9266): 1379-81.
[http://dx.doi.org/10.1016/S0140-6736(00)04616-X] [PMID: 11356429]
[105]
Shimomura I, Hammer RE, Ikemoto S, Brown MS, Goldstein JL. Leptin reverses insulin resistance and diabetes mellitus in mice with congenital lipodystrophy. Nature 1999; 401(6748): 73-6.
[http://dx.doi.org/10.1038/43448] [PMID: 10485707]
[106]
Zimmet PZ, Collins VR, de Courten MP, et al. Mauritius NCD Study Group. Is there a relationship between leptin and insulin sensitivity independent of obesity? A population-based study in the Indian Ocean nation of Mauritius Int J Obes Relat Metab Disord. 1998; 22(2): 171-7.
[http://dx.doi.org/10.1038/sj.ijo.0800559] [PMID: 9504325]
[107]
Donahue RP, Prineas RJ, Donahue RD, et al. Is fasting leptin associated with insulin resistance among nondiabetic individuals? The Miami Community Health Study. Diabetes Care 1999; 22(7): 1092-6.
[http://dx.doi.org/10.2337/diacare.22.7.1092] [PMID: 10388973]
[108]
McNeely MJ, Boyko EJ, Weigle DS, et al. Association between baseline plasma leptin levels and subsequent development of diabetes in Japanese Americans. Diabetes Care 1999; 22(1): 65-70.
[http://dx.doi.org/10.2337/diacare.22.1.65] [PMID: 10333905]
[109]
Welsh P, Murray HM, Buckley BM, et al. Leptin predicts diabetes but not cardiovascular disease: results from a large prospective study in an elderly population. Diabetes Care 2009; 32(2): 308-10.
[http://dx.doi.org/10.2337/dc08-1458] [PMID: 19001191]
[110]
Popovic D, Tomic D, Mitrovic M, Icin T, Bajkin I, Srdic-Galic B, et al. Leptin Resistance and Insulin Resistance Go Hand In Hand, but Lipids are Left Behind JJ Diab Endocrin 2015; 2(1): 008.
[111]
Osegbe I, Okpara H, Azinge E. Relationship between serum leptin and insulin resistance among obese Nigerian women. Ann Afr Med 2016; 15(1): 14-9.
[http://dx.doi.org/10.4103/1596-3519.158524] [PMID: 26857932]
[112]
Jazet IM, Fogteloo AJ, Meinders AE. The relation between leptin and insulin remains when insulin secretion is disturbed. Eur J Intern Med 2006; 17(2): 109-14.
[http://dx.doi.org/10.1016/j.ejim.2005.11.003] [PMID: 16490687]
[113]
Moonishaa TM, Nanda SK, Shamraj M, Sivaa R, Sivakumar P, Ravichandran K. Evaluation of Leptin as a Marker of Insulin Resistance in Type 2 Diabetes Mellitus. Int J Appl Basic Med Res 2017; 7(3): 176-80.
[http://dx.doi.org/10.4103/ijabmr.IJABMR_278_16] [PMID: 28904917]
[114]
Chan JL, Blüher S, Yiannakouris N, Suchard MA, Kratzsch J, Mantzoros CS. Regulation of circulating soluble leptin receptor levels by gender, adiposity, sex steroids, and leptin: observational and interventional studies in humans. Diabetes 2002; 51(7): 2105-12.
[http://dx.doi.org/10.2337/diabetes.51.7.2105] [PMID: 12086939]
[115]
Zastrow O, Seidel B, Kiess W, et al. The soluble leptin receptor is crucial for leptin action: evidence from clinical and experimental data. Int J Obes Relat Metab Disord 2003; 27(12): 1472-8.
[http://dx.doi.org/10.1038/sj.ijo.0802432] [PMID: 14634677]
[116]
Kratzsch J, Lammert A, Bottner A, et al. Circulating soluble leptin receptor and free leptin index during childhood, puberty, and adolescence. J Clin Endocrinol Metab 2002; 87(10): 4587-94.
[http://dx.doi.org/10.1210/jc.2002-020001] [PMID: 12364439]
[117]
Herrick JE, Panza GS, Gollie JM. Leptin, Leptin Soluble Receptor, and the Free Leptin Index following a Diet and Physical Activity Lifestyle Intervention in Obese Males and Females. J Obes 2016; 2016 8375828
[http://dx.doi.org/10.1155/2016/8375828] [PMID: 28050279]
[118]
Donoso MA, Muñoz-Calvo MT, Barrios V, Martínez G, Hawkins F, Argente J. Increased leptin/adiponectin ratio and free leptin index are markers of insulin resistance in obese girls during pubertal development. Horm Res Paediatr 2013; 80(5): 363-70.
[http://dx.doi.org/10.1159/000356046] [PMID: 24217338]
[119]
Cernea S, Roiban AL, Both E, Huţanu A. Serum leptin and leptin resistance correlations with NAFLD in patients with type 2 diabetes. Diabetes Metab Res Rev 2018; 34(8) e3050
[http://dx.doi.org/10.1002/dmrr.3050] [PMID: 30052309]
[120]
Myers MG Jr, Leibel RL, Seeley RJ, Schwartz MW. Obesity and leptin resistance: distinguishing cause from effect. Trends Endocrinol Metab 2010; 21(11): 643-51.
[http://dx.doi.org/10.1016/j.tem.2010.08.002] [PMID: 20846876]
[121]
Myers MG Jr, Heymsfield S, Haft C, Kahn B, Laughlin M, Leibel R, et al. Defining Clinical Leptin Resistance - Challenges and Opportunities. Cell Metab 2012; 15(2): 150-6.
[http://dx.doi.org/10.1016/j.cmet.2012.01.002] [PMID: 22326217]
[122]
Flier JS, Maratos-Flier E. Leptin’s Physiologic Role: Does the Emperor of Energy Balance Have No Clothes? Cell Metab 2017; 26(1): 24-6.
[http://dx.doi.org/10.1016/j.cmet.2017.05.013] [PMID: 28648981]
[123]
Flier JS. Starvation in the Midst of Plenty: Reflections on the History and Biology of Insulin and Leptin. Endocr Rev 2019; 40(1): 1-16.
[http://dx.doi.org/10.1210/er.2018-00179] [PMID: 30357355]
[124]
Tabe-Bordbar S, Anastasio TJ. Computational Analysis of the Hypothalamic Control of Food Intake. Front Comput Neurosci 2016; 10: 27.
[http://dx.doi.org/10.3389/fncom.2016.00027] [PMID: 27199725]
[125]
Beuter A. The use of neurocomputational models as alternatives to animal models in the development of electrical brain stimulation treatments. Altern Lab Anim 2017; 45(2): 91-9.
[http://dx.doi.org/10.1177/026119291704500203] [PMID: 28598194]
[126]
Jacquier M, Soula HA, Crauste F. A mathematical model of leptin resistance. Math Biosci 2015; 267: 10-23.
[http://dx.doi.org/10.1016/j.mbs.2015.06.008] [PMID: 26116428]
[127]
Zhang L, Song H, Ge Y, Ji G, Yao Z. Temporal relationship between diet-induced steatosis and onset of insulin/leptin resistance in male Wistar rats. PLoS One 2015; 10(2) e0117008
[http://dx.doi.org/10.1371/journal.pone.0117008] [PMID: 25658428]
[128]
Heymsfield SB, Greenberg AS, Fujioka K, et al. Recombinant leptin for weight loss in obese and lean adults: a randomized, controlled, dose-escalation trial. JAMA 1999; 282(16): 1568-75.
[http://dx.doi.org/10.1001/jama.282.16.1568] [PMID: 10546697]
[129]
Mittendorfer B, Horowitz JF, DePaoli AM, McCamish MA, Patterson BW, Klein S. Recombinant human leptin treatment does not improve insulin action in obese subjects with type 2 diabetes. Diabetes 2011; 60(5): 1474-7.
[http://dx.doi.org/10.2337/db10-1302] [PMID: 21411512]
[130]
Vasandani C, Clark GO, Adams-Huet B, Quittner C, Garg A. Efficacy and safety of metreleptin therapy in patients with type 1 diabetes: a pilot study 2017.
[131]
Coppari R, Bjørbæk C. Leptin revisited: its mechanism of action and potential for treating diabetes. Nat Rev Drug Discov 2012; 11(9): 692-708.
[http://dx.doi.org/10.1038/nrd3757] [PMID: 22935803]
[132]
Berger SE, Huggins GS, McCaffery JM, Jacques PF, Lichtenstein AH. Change in Cardiometabolic Risk Factors Associated With Magnitude of Weight Regain 3 Years After a 1-Year Intensive Lifestyle Intervention in Type 2 Diabetes Mellitus: The Look AHEAD Trial. J Am Heart Assoc 2019; 8(20) e010951
[http://dx.doi.org/10.1161/JAHA.118.010951] [PMID: 31594431]
[133]
Santoro A, Mattace Raso G, Meli R. Drug targeting of leptin resistance. Life Sci 2015; 140: 64-74.
[http://dx.doi.org/10.1016/j.lfs.2015.05.012] [PMID: 26071010]
[134]
Pandey NR, Zhou X, Qin Z, et al. The LIM domain only 4 protein is a metabolic responsive inhibitor of protein tyrosine phosphatase 1B that controls hypothalamic leptin signaling. J Neurosci 2013; 33(31): 12647-55.
[http://dx.doi.org/10.1523/JNEUROSCI.0746-13.2013] [PMID: 23904601]
[135]
Goldstein BJ. Protein-tyrosine phosphatase 1B (PTP1B): a novel therapeutic target for type 2 diabetes mellitus, obesity and related states of insulin resistance. Curr Drug Targets Immune Endocr Metabol Disord 2001; 1(3): 265-75.
[http://dx.doi.org/10.2174/1568008013341163] [PMID: 12477292]
[136]
Zasloff M, Williams JI, Chen Q, et al. A spermine-coupled cholesterol metabolite from the shark with potent appetite suppressant and antidiabetic properties. Int J Obes Relat Metab Disord 2001; 25(5): 689-97.
[http://dx.doi.org/10.1038/sj.ijo.0801599] [PMID: 11360152]
[137]
Lantz KA, Hart SG, Planey SL, et al. Inhibition of PTP1B by trodusquemine (MSI-1436) causes fat-specific weight loss in diet-induced obese mice. Obesity (Silver Spring) 2010; 18(8): 1516-23.
[http://dx.doi.org/10.1038/oby.2009.444] [PMID: 20075852]
[138]
Ahima RS, Patel HR, Takahashi N, Qi Y, Hileman SM, Zasloff MA. Appetite suppression and weight reduction by a centrally active aminosterol. Diabetes 2002; 51(7): 2099-104.
[http://dx.doi.org/10.2337/diabetes.51.7.2099] [PMID: 12086938]
[139]
Zinker BA, Rondinone CM, Trevillyan JM, et al. PTP1B antisense oligonucleotide lowers PTP1B protein, normalizes blood glucose, and improves insulin sensitivity in diabetic mice. Proc Natl Acad Sci USA 2002; 99(17): 11357-62.
[http://dx.doi.org/10.1073/pnas.142298199] [PMID: 12169659]
[140]
Koizumi M, Takagi-Sato M, Okuyama R, Araki K, Sun W, Nakai D. In vivo antisense activity of ENA oligonucleotides targeting PTP1B mRNA in comparison of that of 2′-MOE-modified oligonucleotides. Nucleic Acids Symp Ser (Oxf) 2007; 51(51): 111-2.
[http://dx.doi.org/10.1093/nass/nrm056] [PMID: 18029611]
[141]
Qin Z, Pandey NR, Zhou X, et al. Functional properties of Claramine: a novel PTP1B inhibitor and insulin-mimetic compound. Biochem Biophys Res Commun 2015; 458(1): 21-7.
[http://dx.doi.org/10.1016/j.bbrc.2015.01.040] [PMID: 25623533]
[142]
Krishnan N, Konidaris KF, Gasser G, Tonks NK. A potent, selective, and orally bioavailable inhibitor of the protein-tyrosine phosphatase PTP1B improves insulin and leptin signaling in animal models. J Biol Chem 2018; 293(5): 1517-25.
[http://dx.doi.org/10.1074/jbc.C117.819110] [PMID: 29217773]
[143]
Franco JG, Dias-Rocha CP, Fernandes TP, et al. Resveratrol treatment rescues hyperleptinemia and improves hypothalamic leptin signaling programmed by maternal high-fat diet in rats. Eur J Nutr 2016; 55(2): 601-10.
[http://dx.doi.org/10.1007/s00394-015-0880-7] [PMID: 25801629]
[144]
Ibars M, Ardid-Ruiz A, Suárez M, Muguerza B, Bladé C, Aragonès G. Proanthocyanidins potentiate hypothalamic leptin/STAT3 signalling and Pomc gene expression in rats with diet-induced obesity. Int J Obes 2017; 41(1): 129-36.
[http://dx.doi.org/10.1038/ijo.2016.169] [PMID: 27677620]
[145]
Lutz TA. Amylinergic control of food intake. Physiol Behav 2006; 89(4): 465-71.
[http://dx.doi.org/10.1016/j.physbeh.2006.04.001] [PMID: 16697020]
[146]
Roth JD, Roland BL, Cole RL, et al. Leptin responsiveness restored by amylin agonism in diet-induced obesity: evidence from nonclinical and clinical studies. Proc Natl Acad Sci USA 2008; 105(20): 7257-62.
[http://dx.doi.org/10.1073/pnas.0706473105] [PMID: 18458326]
[147]
Trevaskis JL, Coffey T, Cole R, et al. Amylin-mediated restoration of leptin responsiveness in diet-induced obesity: magnitude and mechanisms. Endocrinology 2008; 149(11): 5679-87.
[http://dx.doi.org/10.1210/en.2008-0770] [PMID: 18669592]
[148]
Trevaskis JL, Lei C, Koda JE, Weyer C, Parkes DG, Roth JD. Interaction of leptin and amylin in the long-term maintenance of weight loss in diet-induced obese rats. Obesity (Silver Spring) 2010; 18(1): 21-6.
[http://dx.doi.org/10.1038/oby.2009.187] [PMID: 19543217]
[149]
Le Foll C, Johnson MD, Dunn-Meynell AA, Boyle CN, Lutz TA, Levin BE. Amylin-induced central IL-6 production enhances ventromedial hypothalamic leptin signaling. Diabetes 2015; 64(5): 1621-31.
[http://dx.doi.org/10.2337/db14-0645] [PMID: 25409701]
[150]
Lutz TA, Coester B, Whiting L, et al. Amylin selectively signals onto POMC neurons in the arcuate nucleus of the hypothalamus. Diabetes 2018; 67(5): 805-17.
[http://dx.doi.org/10.2337/db17-1347] [PMID: 29467172]
[151]
Trevaskis JL, Wittmer C, Athanacio J, Griffin PS, Parkes DG, Roth JD. Amylin/leptin synergy is absent in extreme obesity and not restored by calorie restriction-induced weight loss in rats. Obes Sci Pract 2016; 2(4): 385-91.
[http://dx.doi.org/10.1002/osp4.62] [PMID: 28090343]
[152]
Müller TD, Sullivan LM, Habegger K, et al. Restoration of leptin responsiveness in diet-induced obese mice using an optimized leptin analog in combination with exendin-4 or FGF21. J Pept Sci 2012; 18(6): 383-93.
[http://dx.doi.org/10.1002/psc.2408] [PMID: 22565812]
[153]
Kim YW, Kim JY, Park YH, et al. Metformin restores leptin sensitivity in high-fat-fed obese rats with leptin resistance. Diabetes 2006; 55(3): 716-24.
[http://dx.doi.org/10.2337/diabetes.55.03.06.db05-0917] [PMID: 16505235]
[154]
Ida S, Murata K, Kaneko R. Effects of pioglitazone treatment on blood leptin levels in patients with type 2 diabetes. J Diabetes Investig 2018; 9(4): 917-24.
[http://dx.doi.org/10.1111/jdi.12783] [PMID: 29194996]
[155]
Iepsen EW, Lundgren J, Dirksen C, et al. Treatment with a GLP-1 receptor agonist diminishes the decrease in free plasma leptin during maintenance of weight loss. Int J Obes 2015; 39(5): 834-41.
[http://dx.doi.org/10.1038/ijo.2014.177] [PMID: 25287751]
[156]
Kanoski SE, Ong ZY, Fortin SM, Schlessinger ES, Grill HJ. Liraglutide, leptin and their combined effects on feeding: additive intake reduction through common intracellular signalling mechanisms. Diabetes Obes Metab 2015; 17(3): 285-93.
[http://dx.doi.org/10.1111/dom.12423] [PMID: 25475828]
[157]
Clemmensen C, Chabenne J, Finan B, et al. GLP-1/glucagon coagonism restores leptin responsiveness in obese mice chronically maintained on an obesogenic diet. Diabetes 2014; 63(4): 1422-7.
[http://dx.doi.org/10.2337/db13-1609] [PMID: 24379349]
[158]
Andreoli MF, Donato J, Cakir I, Perello M. Leptin resensitisation: a reversion of leptin-resistant states. J Endocrinol 2019; 241(3): R81-96.
[http://dx.doi.org/10.1530/JOE-18-0606] [PMID: 30959481]
[159]
Kars M, Yang L, Gregor MF, et al. Tauroursodeoxycholic Acid may improve liver and muscle but not adipose tissue insulin sensitivity in obese men and women. Diabetes 2010; 59(8): 1899-905.
[http://dx.doi.org/10.2337/db10-0308] [PMID: 20522594]
[160]
Xiao C, Giacca A, Lewis GF. Sodium phenylbutyrate, a drug with known capacity to reduce endoplasmic reticulum stress, partially alleviates lipid-induced insulin resistance and beta-cell dysfunction in humans. Diabetes 2011; 60(3): 918-24.
[http://dx.doi.org/10.2337/db10-1433] [PMID: 21270237]
[161]
Facey A, Dilworth L, Irving R. A Review of the Leptin Hormone and the Association with Obesity and Diabetes Mellitus. J Diabetes Metab 2017; 8: 3.
[http://dx.doi.org/10.4172/2155-6156.1000727]
[162]
Jeong YT, Kim YD, Jung YM, et al. Low molecular weight fucoidan improves endoplasmic reticulum stress-reduced insulin sensitivity through AMP-activated protein kinase activation in L6 myotubes and restores lipid homeostasis in a mouse model of type 2 diabetes. Mol Pharmacol 2013; 84(1): 147-57.
[http://dx.doi.org/10.1124/mol.113.085100] [PMID: 23658008]
[163]
Hosoi T, Yamaguchi R, Noji K, et al. Flurbiprofen ameliorated obesity by attenuating leptin resistance induced by endoplasmic reticulum stress. EMBO Mol Med 2014; 6(3): 335-46.
[http://dx.doi.org/10.1002/emmm.201303227] [PMID: 24421337]

Rights & Permissions Print Cite
Article Metrics
16
© 2024 Bentham Science Publishers | Privacy Policy