The role of adipose tissue in cardiovascular health and disease

Abstract

Accumulating knowledge on the biology and function of the adipose tissue has led to a major shift in our understanding of its role in health and disease. The adipose tissue is now recognized as a crucial regulator of cardiovascular health, through the secretion of several bioactive products, including adipocytokines, microvesicles, and gaseous messengers, with a wide range of endocrine and paracrine effects on the cardiovascular system. The adipose tissue function and secretome are tightly controlled by complex homeostatic mechanisms and local cell-cell interactions, which can become dysregulated in obesity. Systemic or local inflammation and insulin resistance lead to a shift in the adipose tissue secretome from anti-inflammatory and anti-atherogenic towards a pro-inflammatory and pro-atherogenic profile. Moreover, the interplay between the adipose tissue and the cardiovascular system is bidirectional, with vascular-derived and heart-derived signals directly affecting adipose tissue biology. In this Review, we summarize the current knowledge on the biology and regional variability of adipose tissue in humans, deciphering the complex molecular mechanisms controlling the crosstalk between the adipose tissue and the cardiovascular system, and their possible clinical translation. In addition, we highlight the latest developments in adipose tissue imaging for cardiovascular risk stratification, and discuss how therapeutic targeting of the adipose tissue can improve prevention and treatment of cardiovascular disease.

High-Risk Atherosclerosis and Metabolic Phenotype: The Roles of Ectopic Adiposity, Atherogenic Dyslipidemia, and Inflammation

“…8 High-risk atherosclerosis is closely associated with a cluster of metabolic and inflammatory features of a phenotype characterized by an increase of ectopic body fat. 9,10 Figure 1 depicts a conceptual framework of how the accumulation of dysfunctional, ectopic fat in the abdominal cavity (visceral fat) and in organs (pericardium, liver, pancreas, and skeletal muscle)-in particular if accompanied by sarcopenia 11,12 contributes to a proatherogenic and procoagulatory state 9,10,13 and drives high-risk atherosclerosis through multiorgan/tissue involvement. Figure 1 furthermore maps the links between each of the elements within this framework.…”

“…10,14 AT secretome. While subcutaneous AT is largely neutral, or in the case of lower body AT even protective with respect to cardiovascular risk, 15 expansion of visceral and/or ectopic dysfunctional AT is closely linked to poor cardiometabolic health and MetS 9,16 (Fig. 1A).…”

“…1A). Factors that promote AT dysfunction are chronic positive energy balance in conjunction with biochemical stressors, including physical inactivity, 9 poor diet quality, 9 active/passive exposure to cigarette smoke, 17 and sleep deprivation. 18 Free fatty acid-induced cellular stress causes remodeling of AT and encompasses a set of changes, including AT inflammation and altered secretome and modulation of the browning phenotype.…”

“…AT phenotype can be modified upon lifestyle interventions. Physical exercise, 9 intermittent fasting, 25,26 diet quality, 9 and regular circadian rhythms/restorative sleep 18 promote the preservation of a healthy AT phenotype and have the potential to reverse AT dysfunction and related cardiometabolic risk. These effects occur largely independent of body mass index (BMI).…”

“…These effects occur largely independent of body mass index (BMI). 9,16 The CENTRAL-MRI trial demonstrated that in a group of 278 sedentary adults (age = 48 years, 89% men, BMI 30.8 kg/m 2 ) with abdominal obesity (75%) or dyslipidemia, a Mediterranean lowcarbohydrate dietary pattern was superior to a low-fat diet in decreasing intrahepatic, intrapericardial, and pancreatic fat (P < 0.05 for all), and that exercise had an independent contribution to visceral AT loss. 27 Further to that, mobilization of ectopic fat depots was associated with improved cardiometabolic surrogate markers such as decreased expression of atherogenic dyslipidemia.…”