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

The Metabolic Syndrome Puzzles; Possible Pathogenesis and Management

Author(s): Basheer Abdullah Marzoog*

Volume 19, Issue 4, 2023

Published on: 07 July, 2022

Article ID: e290422204258 Pages: 8

DOI: 10.2174/1573399818666220429100411

Price: $65

Abstract

Background and Aims: Metabolic syndrome is a multifactorial pathophysiological process with complicated homeostatic disorders that arise from various systematic metabolic defects. Various theories underlie the development of metabolic syndrome but are fully not understood.

Methods: Revising PubMed and Scopus literature data on metabolic syndrome pathogenesis and management.

Results: The most accepted hypothesis is that a cluster of risk factors combined to obtain a truly metabolic syndrome. The pathophysiology of the metabolic syndrome depends on the underlying development path due to insulin resistance or chronic inflammation and is usually combined with neurohormonal disturbance. Meanwhile, these defects can be inherited via loss of function of certain genes that lead to severe obesity, early diabetes, or severe insulin resistance (with or without lipodystrophy). Chronic inflammation is also a driver of metabolic syndrome. Lifestyle is still the therapy of choice in managing metabolic syndrome, but unfortunately, during the lockdown, most people could not reserve a healthy regime; therefore, it can also be referred to as a pandemic with COVID-19.

Conclusions: This powerful illustration shows how defects in specific encoded proteins located predominantly in the brain, pancreatic beta-cell, muscle, or fat give rise to these distinct components of the metabolic syndrome. Primarily, obesity and its sequela are the initiators of metabolic syndrome. The presence of metabolic syndrome increases the risk and severity of other pathologies' emergence, even in non-related metabolic syndrome diseases such as COVID-19. The article provides new insights into the pathogeneses and management of the metabolic syndrome.

Keywords: Metabolic syndrome & dysmetabolic syndrome, hypertriglyceridemic waist, insulin resistance syndrome, obesity syndrome, syndrome X, pathogenesis & pathophysiology.

[1]
Belenkov YN, Privalova EV, Kaplunova VY, et al. Metabolic syndrome: Development of the issue, main diagnostic criteria. Ration Pharmacother Cardiol 2018; 14(5): 757-64.
[http://dx.doi.org/10.20996/1819-6446-2018-14-5-757-764]
[2]
Alberti KGMM, Eckel RH, Grundy SM, et al. Harmonizing the metabolic syndrome: A joint interim statement of the international diabetes federation task force on epidemiology and prevention; national heart, lung, and blood institute; American heart association; World heart federation; International atherosclerosis society; and international association for the study of obesity. Circulation 2009; 120(16): 1640-5.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.109.192644] [PMID: 19805654]
[3]
Engin A. The definition and prevalence of obesity and metabolic syndrome. Adv Exp Med Biol 2017; 960: 1-17.
[http://dx.doi.org/10.1007/978-3-319-48382-5_1] [PMID: 28585193]
[4]
Aganović I, Dušek T. Pathophysiology of metabolic syndrome. EJIFCC 2007; 18(1): 3-6.
[PMID: 29632461]
[5]
Kaur J. A comprehensive review on metabolic syndrome. Cardiol Res Pract 2014; 2014: 943162.
[http://dx.doi.org/10.1155/2014/943162] [PMID: 24711954]
[6]
Després J-P, Lemieux I. Abdominal obesity and metabolic syndrome. Nature 2006; 444(7121): 881-7.
[http://dx.doi.org/10.1038/nature05488] [PMID: 17167477]
[7]
Chassaing B, Koren O, Goodrich JK, et al. Dietary emulsifiers impact the mouse gut microbiota promoting colitis and metabolic syn-drome. Nature 2015; 519(7541): 92-6.
[http://dx.doi.org/10.1038/nature14232] [PMID: 25731162]
[8]
Huang PL. A comprehensive definition for metabolic syndrome. Dis Model Mech 2009; 2(5-6): 231-7.
[http://dx.doi.org/10.1242/dmm.001180] [PMID: 19407331]
[9]
Walker BR, Colledge NR, Ralston SH, Penman ID. Davidson’s Principles & practice of medicine. Edinburgh: Churchill Livingstone Else-vier 2014.
[10]
Bonsignore MR, Steiropoulos P. Metabolic syndrome. Obstructive sleep apnoea. European Respiratory Society 2015; pp. 221-37.
[http://dx.doi.org/10.1183/2312508X.10006014]
[11]
Obesity and overweight. 2020. Available from: https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight (accessed Oct 30, 2020).
[12]
NHLBI. Metabolic Syndrome | NHLBI. NIH Available from: https://www.nhlbi.nih.gov/health-topics/metabolic-syndrome (accessed Oct 17, 2020).
[13]
Kim MK, Reaven GM, Chen Y-DDI, Kim E, Kim SH. Hyperinsulinemia in individuals with obesity: Role of insulin clearance. Obesity (Silver Spring) 2015; 23(12): 2430-4.
[http://dx.doi.org/10.1002/oby.21256] [PMID: 26524351]
[14]
Lanktree MB, Hegele RA. Metabolic syndrome. In: David SP, Ed. Genomic and precision medicine. Amsterdam: Elsevier 2017; pp. 283-99.
[http://dx.doi.org/10.1016/B978-0-12-800685-6.00015-1]
[15]
Wong SK, Chin K-Y, Suhaimi FH, Fairus A, Ima-Nirwana S. Animal models of metabolic syndrome: A review. Nutr Metab (Lond) 2016; 13(1): 65.
[http://dx.doi.org/10.1186/s12986-016-0123-9] [PMID: 27708685]
[16]
Miranda PJ, DeFronzo RA, Califf RM, Guyton JR. Metabolic syndrome: Definition, pathophysiology, and mechanisms. Am Heart J 2005; 149(1): 33-45.
[http://dx.doi.org/10.1016/j.ahj.2004.07.013]
[17]
Byrne CD, Wild SH. The metabolic syndrome. Hoboken, New Jersey: Wiley Online Library 2011.
[http://dx.doi.org/10.1002/9781444347319]
[18]
McCracken E, Monaghan M, Sreenivasan S. Pathophysiology of the metabolic syndrome. Clin Dermatol 2018; 36(1): 14-20.
[http://dx.doi.org/10.1016/j.clindermatol.2017.09.004] [PMID: 29241747]
[19]
Choi SM, Tucker DF, Gross DN, et al. Insulin regulates adipocyte lipolysis via an Akt-independent signaling pathway. Mol Cell Biol 2010; 30(21): 5009-20.
[http://dx.doi.org/10.1128/MCB.00797-10] [PMID: 20733001]
[20]
Kassi E, Pervanidou P, Kaltsas G, Chrousos G. Metabolic syndrome: Definitions and controversies. BMC Med 2011; 9(1): 48.
[http://dx.doi.org/10.1186/1741-7015-9-48] [PMID: 21542944]
[21]
Vijay-Kumar M, Aitken J D, Carvalho F A, et al. Metabolic syndrome and altered gut microbiota in mice lacking toll-like receptor 5. Science 2010; 328(5975): 228-31.
[http://dx.doi.org/10.1126/science.1179721]
[22]
Maury E, Brichard SM. Adipokine dysregulation, adipose tissue inflammation and metabolic syndrome. Mol Cell Endocrinol 2010; 314(1): 1-16.
[http://dx.doi.org/10.1016/j.mce.2009.07.031] [PMID: 19682539]
[23]
Bao P, Liu G, Wei Y. Association between IL-6 and related risk factors of metabolic syndrome and cardiovascular disease in young rats. Int J Clin Exp Med 2015; 8(8): 13491-9.
[PMID: 26550286]
[24]
Alessi M-C, Juhan-Vague I. PAI-1 and the metabolic syndrome: Links, causes, and consequences. Arterioscler Thromb Vasc Biol 2006; 26(10): 2200-7.
[http://dx.doi.org/10.1161/01.ATV.0000242905.41404.68] [PMID: 16931789]
[25]
Rochlani Y, Pothineni NV, Kovelamudi S, Mehta JL. Metabolic syndrome: Pathophysiology, management, and modulation by natural compounds. Ther Adv Cardiovasc Dis 2017; 11(8): 215-25.
[http://dx.doi.org/10.1177/1753944717711379]
[26]
Unger RH, Clark GO, Scherer PE, Orci L. Lipid homeostasis, lipotoxicity and the metabolic syndrome. Biochim Biophys Acta 2010; 1801(3): 209-14.
[http://dx.doi.org/10.1016/j.bbalip.2009.10.006] [PMID: 19948243]
[27]
Appel SJ, Harrell JS, Davenport ML. Central obesity, the metabolic syndrome, and plasminogen activator inhibitor-1 in young adults. J Am Acad Nurse Pract 2005; 17(12): 535-41.
[http://dx.doi.org/10.1111/j.1745-7599.2005.00083.x] [PMID: 16293162]
[28]
Murphy R, Carroll RW, Krebs JD. Pathogenesis of the metabolic syndrome: Insights from monogenic disorders. Mediators Inflamm 2013; 2013: 920214.
[http://dx.doi.org/10.1155/2013/920214] [PMID: 23766565]
[29]
Stanikova D, Surova M, Ticha L, et al. Melanocortin-4 receptor gene mutations in obese Slovak children. Physiol Res 2015; 64(6): 883-90.
[http://dx.doi.org/10.33549/physiolres.932968] [PMID: 26047380]
[30]
Sáinz N, González-Navarro CJ, Martínez JA, Moreno-Aliaga MJ. Leptin signaling as a therapeutic target of obesity. Expert Opin Ther Targets 2015; 19(7): 893-909.
[http://dx.doi.org/10.1517/14728222.2015.1018824] [PMID: 25726860]
[31]
Monteiro R, Azevedo I. Chronic inflammation in obesity and the metabolic syndrome. Mediators Inflamm 2010; 2010: 1-10.
[http://dx.doi.org/10.1155/2010/289645] [PMID: 20706689]
[32]
Costantini S, Sharma A, Colonna G. The value of the cytokinome profile. In: Nagal A, Ed. inflammatory disease - A modern perspective. London, UK: IntechOpen 2011.
[http://dx.doi.org/10.5772/25707]
[33]
Mizumura K, Choi AMK, Ryter SW. Emerging role of selective autophagy in human diseases. Front Pharmacol 2014; 5: 244.
[http://dx.doi.org/10.3389/fphar.2014.00244] [PMID: 25414669]
[34]
Yang Y, Jiang G, Zhang P, Fan J. Programmed cell death and its role in inflammation. Mil Med Res 2015; 2(1): 12.
[http://dx.doi.org/10.1186/s40779-015-0039-0] [PMID: 26045969]
[35]
Nailwal H, Chan FK-M. Necroptosis in anti-viral inflammation. Cell Death Differ 2019; 26(1): 4-13.
[http://dx.doi.org/10.1038/s41418-018-0172-x] [PMID: 30050058]
[36]
Jorgensen I, Miao EA. Pyroptotic cell death defends against intracellular pathogens. Immunol Rev 2015; 265(1): 130-42.
[http://dx.doi.org/10.1111/imr.12287] [PMID: 25879289]
[37]
Gray J, Yeo GSH, Cox JJ, et al. Hyperphagia, severe obesity, impaired cognitive function, and hyperactivity associated with functional loss of one copy of the Brain-Derived Neurotrophic Factor (BDNF) gene. Diabetes 2006; 55(12): 3366-71.
[http://dx.doi.org/10.2337/db06-0550] [PMID: 17130481]
[38]
Yeo GSH, Connie Hung C-C, Rochford J, et al. A de novo mutation affecting human TrkB associated with severe obesity and developmental delay. Nat Neurosci 2004; 7(11): 1187-9.
[http://dx.doi.org/10.1038/nn1336] [PMID: 15494731]
[39]
Festi D, Schiumerini R, Eusebi LH, Marasco G, Taddia M, Colecchia A. Gut microbiota and metabolic syndrome. World J Gastroenterol 2014; 20(43): 16079-94.
[http://dx.doi.org/10.3748/wjg.v20.i43.16079] [PMID: 25473159]
[40]
Tilg H, Kaser A. Gut microbiome, obesity, and metabolic dysfunction. J Clin Invest 2011; 121(6): 2126-32.
[http://dx.doi.org/10.1172/JCI58109] [PMID: 21633181]
[41]
Tomas E, Stanojevic V, McManus K, et al. GLP-1(32-36)amide pentapeptide increases basal energy expenditure and inhibits weight gain in obese mice. Diabetes 2015; 64(7): 2409-19.
[http://dx.doi.org/10.2337/db14-1708] [PMID: 25858562]
[42]
Armani A, Berry A, Cirulli F, Caprio M. Molecular mechanisms underlying metabolic syndrome: The expanding role of the adipocyte. FASEB J 2017; 31(10): 4240-55.
[http://dx.doi.org/10.1096/fj.201601125RRR] [PMID: 28705812]
[43]
Yanai H. Metabolic syndrome and COVID-19. Cardiol Res 2020; 11(6): 360-5.
[http://dx.doi.org/10.14740/cr1181] [PMID: 33224380]
[44]
Ghoneim S, Butt MU, Hamid O, Shah A, Asaad I. The incidence of COVID-19 in patients with metabolic syndrome and non-alcoholic steatohepatitis: A population-based study. Metab Open 2020; 8: 100057.
[http://dx.doi.org/10.1016/j.metop.2020.100057] [PMID: 32924000]
[45]
Tumova J, Andel M, Trnka J. Excess of free fatty acids as a cause of metabolic dysfunction in Skeletal Muscle. Physiol Res 2016; 65: 193-207.
[http://dx.doi.org/10.33549/physiolres.932993]
[46]
Singh RB, Pella D, Mechirova V, Otsuka K. Can brain dysfunction be a predisposing factor for metabolic syndrome? Biomed Pharmacother 2004; 58 (Suppl. 1): S56-68.
[http://dx.doi.org/10.1016/S0753-3322(04)80011-8] [PMID: 15754841]
[47]
Beigh SH, Jain S. Prevalence of metabolic syndrome and gender differences. Bioinformation 2012; 8(13): 613-6.
[http://dx.doi.org/10.6026/97320630008613] [PMID: 22829741]
[48]
Rochlani Y, Pothineni NV, Mehta JL. Metabolic syndrome: Does it differ between women and men? Cardiovasc Drugs Ther 2015; 29(4): 329-38.
[http://dx.doi.org/10.1007/s10557-015-6593-6] [PMID: 25994831]
[49]
Regitz-Zagrosek V, Lehmkuhl E, Weickert MO. Gender differences in the metabolic syndrome and their role for cardiovascular disease. Clin Res Cardiol 2006; 95(3): 136-47.
[http://dx.doi.org/10.1007/s00392-006-0351-5] [PMID: 16598526]
[50]
Pedersen BK, Saltin B. Exercise as medicine - evidence for prescribing exercise as therapy in 26 different chronic diseases. Scand J Med Sci Sports 2015; 25 (Suppl. 3): 1-72.
[http://dx.doi.org/10.1111/sms.12581] [PMID: 26606383]
[51]
De Sousa SMC, Norman RJ. Metabolic syndrome, diet and exercise. Best Pract Res Clin Obstet Gynaecol 2016; 37: 140-51.
[http://dx.doi.org/10.1016/j.bpobgyn.2016.01.006] [PMID: 26972165]
[52]
Pérez-Rubio KG, González-Ortiz M, Martínez-Abundis E, Robles-Cervantes JA, Espinel-Bermúdez MC. Effect of berberine administration on metabolic syndrome, insulin sensitivity, and insulin secretion. Metab Syndr Relat Disord 2013; 11(5): 366-9.
[http://dx.doi.org/10.1089/met.2012.0183] [PMID: 23808999]
[53]
Padiya R, Khatua TN, Bagul PK, Kuncha M, Banerjee SK. Garlic improves insulin sensitivity and associated metabolic syndromes in fruc-tose fed rats. Nutr Metab (Lond) 2011; 8(1): 53.
[http://dx.doi.org/10.1186/1743-7075-8-53] [PMID: 21794123]
[54]
Leiherer A, Stoemmer K, Muendlein A, et al. Quercetin impacts expression of metabolism- and obesity-associated genes in SGBS adipo-cytes. Nutrients 2016; 8(5): 282.
[http://dx.doi.org/10.3390/nu8050282] [PMID: 27187453]
[55]
Bhat M, Kothiwale SK, Tirmale AR, Bhargava SY, Joshi BN. Antidiabetic properties of Azardiracta indica and Bougainvillea spectabilis: In vivo studies in murine diabetes model. Evidence-Based Complement Altern Med 2011; 2011: 1-9.
[http://dx.doi.org/10.1093/ecam/nep033]
[56]
Gillies PJ, Bhatia SK, Belcher LA, Hannon DB, Thompson JT, Vanden Heuvel JP. Regulation of inflammatory and lipid metabolism genes by eicosapentaenoic acid-rich oil. J Lipid Res 2012; 53(8): 1679-89.
[http://dx.doi.org/10.1194/jlr.M022657] [PMID: 22556214]
[57]
de Souza CG, Sattler JA, de Assis AM, Rech A, Perry MLS, Souza DO. Metabolic effects of sulforaphane oral treatment in streptozotocin-diabetic rats. J Med Food 2012; 15(9): 795-801.
[http://dx.doi.org/10.1089/jmf.2012.0016] [PMID: 22925073]
[58]
Chen S, Zhao X, Ran L, et al. Resveratrol improves insulin resistance, glucose and lipid metabolism in patients with non-alcoholic fatty liver disease: A randomized controlled trial. Dig Liver Dis 2015; 47(3): 226-32.
[http://dx.doi.org/10.1016/j.dld.2014.11.015] [PMID: 25577300]
[59]
Cao H, Graves DJ, Anderson RA. Cinnamon extract regulates glucose transporter and insulin-signaling gene expression in mouse adipocytes. Phytomedicine 2010; 17(13): 1027-32.
[http://dx.doi.org/10.1016/j.phymed.2010.03.023] [PMID: 20554184]
[60]
Aggarwal BB. Targeting inflammation-induced obesity and metabolic diseases by curcumin and other nutraceuticals. Annu Rev Nutr 2010; 30(1): 173-99.
[http://dx.doi.org/10.1146/annurev.nutr.012809.104755] [PMID: 20420526]
[61]
Kalashnikova MF. Metabolic syndrome: A modern view on concept, prevention methods and treatment. Eff Pharmacother Endocrinol 2013; 55(5): 52-63.
[62]
Park H-K, Ahima RS. Physiology of leptin: Energy homeostasis, neuroendocrine function and metabolism. Metabolism 2015; 64(1): 24-34.
[http://dx.doi.org/10.1016/j.metabol.2014.08.004] [PMID: 25199978]
[63]
Paz-Filho G, Mastronardi CA, Licinio J. Leptin treatment: Facts and expectations. Metabolism 2015; 64(1): 146-56.
[http://dx.doi.org/10.1016/j.metabol.2014.07.014] [PMID: 25156686]
[64]
Hoffman EL, VonWald T, Hansen K. The metabolic syndrome. S D Med 2015; (Spec No.): 24-8.
[http://dx.doi.org/10.1210/jcem.89.6.9995]
[65]
Anagnostis P, Selalmatzidou D, Sapranidis M, et al. Comparative effects of sibutramine and orlistat on weight loss, glucose metabolism and leptin levels in non-diabetic obese patients: A prospective study. Indian J Endocrinol Metab 2012; 16(1): 146-7.
[http://dx.doi.org/10.4103/2230-8210.91214] [PMID: 22276270]
[66]
Montan PD, Sourlas A, Olivero J, Silverio D, Guzman E, Kosmas CE. Pharmacologic therapy of obesity: Mechanisms of action and cardiometabolic effects. Ann Transl Med 2019; 7(16): 393-3.
[http://dx.doi.org/10.21037/atm.2019.07.27] [PMID: 31555707]
[67]
Zhang K, Zhou S, Wang C, Xu H, Zhang L. Acupuncture on obesity: Clinical evidence and possible neuroendocrine mechanisms. Evid Based Complement Alternat Med 2018; 2018: 6409389.
[http://dx.doi.org/10.1155/2018/6409389] [PMID: 30013603]
[68]
Vardanyan GS, Harutyunyan HS, Aghajanov MI, Vardanyan RS. Neurochemical regulators of food behavior for pharmacological treat-ment of obesity: Current status and future prospects. Future Med Chem 2020; 12(20): 1865-84.
[http://dx.doi.org/10.4155/fmc-2019-0361] [PMID: 33040605]
[69]
Chen W, Pang Y. Metabolic syndrome and PCOS: Pathogenesis and the role of metabolites. Metabolites 2021; 11(12): 869.
[http://dx.doi.org/10.3390/metabo11120869] [PMID: 34940628]
[70]
Willer CJ, Speliotes EK, Loos RJ, et al. Six new loci associated with body mass index highlight a neuronal influence on body weight regu-lation. Nat Genet 2009; 41(1): 25-34.
[http://dx.doi.org/10.1038/ng.287] [PMID: 19079261]
[71]
McFall-Ngai M, Hadfield MG, Bosch TCG, et al. Animals in a bacterial world, a new imperative for the life sciences. Proc Natl Acad Sci USA 2013; 110(9): 3229-36.
[http://dx.doi.org/10.1073/pnas.1218525110] [PMID: 23391737]
[72]
Maitre Y, Mahalli R, Micheneau P, Delpierre A, Amador G, Denis F. Evidence and therapeutic perspectives in the relationship between the oral microbiome and Alzheimer’s Disease: A systematic review. Int J Environ Res Public Health 2021; 18(21): 11157.
[http://dx.doi.org/10.3390/ijerph182111157] [PMID: 34769677]
[73]
Willyard C. How gut microbes could drive brain disorders. Nature 2021; 590(7844): 22-5.
[http://dx.doi.org/10.1038/d41586-021-00260-3] [PMID: 33536656]
[74]
Finelli C. Metabolic syndrome, Alzheimer’s disease, and COVID 19: A possible correlation. Curr Alzheimer Res 2021; 18(12): 915-24.
[http://dx.doi.org/10.2174/1567205018666211209095652] [PMID: 34886772]
[75]
Yu B, Yu L, Klionsky DJ. Nutrition acquisition by human immunity, transient overnutrition and the cytokine storm in severe cases of COVID-19. Med Hypotheses 2021; 155: 110668.
[http://dx.doi.org/10.1016/j.mehy.2021.110668] [PMID: 34467856]
[76]
Marzoog B A, Vlasova TI. Transcription factors in deriving β cell regeneration: A potential novel therapeutic target. Curr Mol Med 2022; 22(5): 421-30.
[http://dx.doi.org/10.2174/1566524021666210712144638]

Rights & Permissions Print Cite
Article Metrics
1
© 2024 Bentham Science Publishers | Privacy Policy