title: Contribution of Maladaptive Adipose Tissue Expansion to Development of Cardiovascular Disease.
abstract: The overweight and obesity epidemic has led to an increase in the metabolic syndrome and associated cardiovascular disease (CVD). These abnormalities include insulin resistance, type 2 diabetes mellitus, vascular stiffness, hypertension, stroke, and coronary heart disease. Visceral white adipocyte tissue (WAT) expansion and associated fibrosis/stiffness of WAT promote insulin resistance and CVD through increases in proinflammatory adipokines, oxidative stress, activation of renin-angiotensin-aldosterone system, dysregulation of adipocyte apoptosis and autophagy, dysfunctional immune modulation, and adverse changes in the gut microbiome. The expansion of WAT is partly determined by activation of peroxisome proliferator-activated receptor gamma and mammalian target of rapamycin/ribosomal S6 kinase signaling pathways. Further, the chronic activation of these signaling pathways may not only induce adipocyte hypertrophy and fibrosis, but also contribute to systemic inflammation, and impairment of insulin metabolic signaling in fat, liver, and skeletal muscle tissue. Therefore, the interplay of adipocyte dysfunction, maladaptive immune and inflammatory responses, and associated metabolic disorders often coexist leading to systemic low-grade inflammation and insulin resistance that are associated with increased CVD in obese individuals. © 2017 American Physiological Society. Compr Physiol 7:253-262, 2017.
authors.affiliation: Diabetes and Cardiovascular Research Center, University of Missouri School of Medicine, Columbia, Missouri, USA.|Harry S. Truman Memorial Veterans Hospital, Columbia, Missouri, USA.
authors.forename: Guanghong
authors.initials: G
authors.lastname: Jia
authors.affiliation: Diabetes and Cardiovascular Research Center, University of Missouri School of Medicine, Columbia, Missouri, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Jia
authors.affiliation: Diabetes and Cardiovascular Research Center, University of Missouri School of Medicine, Columbia, Missouri, USA.|Department of Medical Pharmacology and Physiology, University of Missouri School of Medicine, Columbia, Missouri, USA.|Dalton Cardiovascular Center, University of Missouri School of Medicine, Columbia, Missouri, USA.|Harry S. Truman Memorial Veterans Hospital, Columbia, Missouri, USA.
authors.forename: James R
authors.initials: JR
authors.lastname: Sowers
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D002318:Cardiovascular Diseases / Q000209:etiology* / Q000517:prevention & control; D006801:Humans; D050177:Overweight / Q000150:complications / Q000175:diagnosis / Q000628:therapy