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Contribution of Maladaptive Adipose Tissue Expansion to Development of Cardiovascular Disease

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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.

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Figure 1. Figure 1. Adipose tissue in the link of obesity and CVD. (A) Expansion of subcutaneous and VAT induces increases in oxidative stress, proinflammatory adipokines, activation of RAAS, dysregulation of adipocyte apoptosis and autophagy, and gut microbiota dysbiosis, resulting in insulin resistance, dyslipidemia, and associated CVD. (B) Interaction of ectopic adiposity and multiorgan dysregulation that is responsible for obesity and CVD. Nonalcoholic fatty liver disease is an important contributor in the obese individuals with CVD. RAAS, renin angiotensin‐aldosterone system; EC, endothelial cell; VSMC, vascular smooth muscle cell.


Figure 1. Adipose tissue in the link of obesity and CVD. (A) Expansion of subcutaneous and VAT induces increases in oxidative stress, proinflammatory adipokines, activation of RAAS, dysregulation of adipocyte apoptosis and autophagy, and gut microbiota dysbiosis, resulting in insulin resistance, dyslipidemia, and associated CVD. (B) Interaction of ectopic adiposity and multiorgan dysregulation that is responsible for obesity and CVD. Nonalcoholic fatty liver disease is an important contributor in the obese individuals with CVD. RAAS, renin angiotensin‐aldosterone system; EC, endothelial cell; VSMC, vascular smooth muscle cell.
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Guanghong Jia, Yan Jia, James R. Sowers. Contribution of Maladaptive Adipose Tissue Expansion to Development of Cardiovascular Disease. Compr Physiol 2016, 7: 253-262. doi: 10.1002/cphy.c160014