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.

Protective effects of Bacillus probiotics against high-fat diet-induced metabolic disorders in mice

“…Adipocyte hypertrophy is a condition of excessive lipid accumulation beyond the adipocyte buffering capacity, which correlates positively with metabolic disorders [31,32]. Hypertrophy of adipocytes ensues various metabolic dysregulations such as tissue hypoxia, endoplasmic reticulum and oxidative stress, chronic inflammation, and ectopic fat deposition [33,34]. In this study, in addition to the significant reduction of hepatic adiposity, Bacillus treatment also exerted a suppressing effect on the adiposity of SAT and MAT (Fig 1B), which was commensurate with significantly reduced adipocyte hypertrophy in SAT and MAT of Bacillus -treated mice (Fig 5A, 5B, 5D and 5E).…”

Regulation of visceral and epicardial adipose tissue for preventing cardiovascular injuries associated to obesity and diabetes

“…Hypertrophic but not hyperplastic adipocytes, were associated with insulin resistance [21]. Thus, VAT become dysfunctional, dysregulating also adipocyte apoptosis and increasing autophagy [22]. The propensity to preferentially accumulate WAT in VAT stores under conditions of excess energy intake is highly variable from one individual to another.…”

Utility of obesity and metabolic dyslipidemia (a non‐insulin based determinate of the metabolic syndrome and insulin resistance) in predicting arterial stiffness

“…In the current study, the investigators report the use of the METS‐IR in a population at risk for CVD correlates with arterial stiffness and is a predictor of incident hypertension . The inclusion of BMI as a surrogate for visceral adiposity in the METS‐IR is relevant as recent data support a strong link between adipose tissue remodeling of both visceral fat and perivascular fat in the development of vascular IR and stiffness (Figure ) . In this regard, dysfunctional metabolic changes in adipose tissue result in altered secretion of bioactive molecules and inflammatory cytokines such as tumor necrosis factor α (TNF‐α), interleukin 6 (IL‐6), angiotensinogen, aldosterone, leptin, resistin, and monocyte chemoattractant protein‐1 (MCP‐1).…”

“…11 The inclusion of BMI as a surrogate for visceral adiposity in the METS-IR is relevant as recent data support a strong link between adipose tissue remodeling of both visceral fat and perivascular fat in the development of vascular IR and stiffness (Figure 1). [12][13][14] In this regard, dysfunctional into peripheral organs, such as the kidney and brain, where there is high flow but low pre-capillary resistance or impedance. This persistent excess pulsatile wave to the end organ, referred to as pulsatility, damages capillaries and thus tissues in these high flow organs and establishes the cardiovascular risk associated with the cardiometabolic syndrome.…”

“…In addition to the role of visceral fat, the importance of perivascular adipose tissue (PVAT) in vascular biology is increasingly recognized. PVAT not only serves as structural support for most arteries but also secretes molecules with paracrine effects on the vasculature . Hyperplasia of PVAT and infiltration of pro‐inflammatory immune cells in PVAT have been demonstrated in obesity and IR .…”