MetS is caused by a combination of genetic[1][2] and environmental factors, namely a high caloric intake and physical inactivity.[3] The resultant excess adiposity — particularly in the intra-abdominal region (i.e., visceral fat) — leads to adipose tissue dysfunction and insulin resistance.
Expansion of visceral fat and insulin resistance increases circulating free fatty acids (FFAs), which infiltrate the liver and skeletal muscle and disrupt glucose and lipid homeostasis.[3] The liver and skeletal muscle respond by increasing the breakdown of FFAs, which results in decreased glucose uptake in muscle along with increased glucose and triglyceride production and increased high-density lipoprotein clearance in the liver.[4][5]
Additionally, expansion of visceral fat causes altered secretion of adipokines (i.e., hormones, cytokines, and other proteins secreted by fat tissue), including increased secretion of pro-inflammatory cytokines (e.g., interleukin-6, tumor necrosis factor alpha) and reduced secretion of adiponectin, contributing to a state of chronic low-grade inflammation and a deterioration in cardiometabolic health.[6]
References
- ^Nagrani R, Foraita R, Gianfagna F, Iacoviello L, Marild S, Michels N, Molnár D, Moreno L, Russo P, Veidebaum T, Ahrens W, Marron MCommon genetic variation in obesity, lipid transfer genes and risk of Metabolic Syndrome: Results from IDEFICS/I.Family study and meta-analysis.Sci Rep.(2020-04-28)
- ^Kristiansson K, Perola M, Tikkanen E, Kettunen J, Surakka I, Havulinna AS, Stancáková A, Barnes C, Widen E, Kajantie E, Eriksson JG, Viikari J, Kähönen M, Lehtimäki T, Raitakari OT, Hartikainen AL, Ruokonen A, Pouta A, Jula A, Kangas AJ, Soininen P, Ala-Korpela M, Männistö S, Jousilahti P, Bonnycastle LL, Järvelin MR, Kuusisto J, Collins FS, Laakso M, Hurles ME, Palotie A, Peltonen L, Ripatti S, Salomaa VGenome-wide screen for metabolic syndrome susceptibility Loci reveals strong lipid gene contribution but no evidence for common genetic basis for clustering of metabolic syndrome traits.Circ Cardiovasc Genet.(2012-Apr-01)
- ^Zafar U, Khaliq S, Ahmad HU, Manzoor S, Lone KPMetabolic syndrome: an update on diagnostic criteria, pathogenesis, and genetic links.Hormones (Athens).(2018-Sep)
- ^Pi-Sunyer FXThe obesity epidemic: pathophysiology and consequences of obesity.Obes Res.(2002-Dec)
- ^Fahed G, Aoun L, Bou Zerdan M, Allam S, Bou Zerdan M, Bouferraa Y, Assi HIMetabolic Syndrome: Updates on Pathophysiology and Management in 2021.Int J Mol Sci.(2022-Jan-12)
- ^André Tchernof, Jean-Pierre DesprésPathophysiology of human visceral obesity: an updatePhysiol Rev.(2013 Jan)