Adipose Tissue Distribution, Inflammation and Its Metabolic Consequences, Including Diabetes and Cardiovascular Disease

Abstract

Adipose tissue plays essential roles in maintaining lipid and glucose homeostasis. To date several types of adipose tissue have been identified, namely white, brown, and beige, that reside in various specific anatomical locations throughout the body. The cellular composition, secretome, and location of these adipose depots define their function in health and metabolic disease. In obesity, adipose tissue becomes dysfunctional, promoting a pro-inflammatory, hyperlipidemic and insulin resistant environment that contributes to type 2 diabetes mellitus (T2DM). Concurrently, similar features that result from adipose tissue dysfunction also promote cardiovascular disease (CVD) by mechanisms that can be augmented by T2DM. The mechanisms by which dysfunctional adipose tissue simultaneously promote T2DM and CVD, focusing on adipose tissue depot-specific adipokines, inflammatory profiles, and metabolism, will be the focus of this review. The impact that various T2DM and CVD treatment strategies have on adipose tissue function and body weight also will be discussed.

Keywords: adipokines; beige adipose tissue; brown adipose tissue; insulin resistance; metabolic syndrome; subcutaneous white adipose tissue; visceral white adipose tissue.

Figure 1

Metabolically healthy obesity (MHO) vs. metabolically unhealthy obesity (MUHO). In comparison with lean metabolically healthy subjects, those with MHO have increased adiposity and BMI, but with reduced systemic inflammation and retained insulin sensitivity, thus defining them as not having metabolic syndrome (MetS). MHO subjects have elevated subcutaneous white adipose tissue (WAT) levels, without excessive accumulation of visceral fat. Their adipokine profile is similar to lean subjects, but with increased leptin, resistin, and FGF21, and decreased adiponectin, which limits their risk of developing type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) in the short term. By contrast, those with MUHO exhibit elevated insulin resistance and systemic inflammation in addition to increased adiposity and BMI over lean controls, contributing to MetS. MUHO individuals have excess subcutaneous and intra-abdominal adipose tissue, with increased hepatic fat and fat distributed amongst other visceral organs. This leads to a dysfunctional adipokine profile, characterized by reduced adiponectin and omentin, with further elevated leptin, resistin, FGF21, and cytokines when compared to lean controls. Thus, MUHO subjects are at risk for developing T2DM and CVD.

Figure 2

Adipose depots and ectopic fat sites and their features that contribute to type 2 diabetes mellitus (T2DM) or cardiovascular disease (CVD). Features of intra-abdominal white adipose tissue (WAT), subcutaneous fat, hepatic fat, heart and arterial fat (inclusive of epicardial, pericardial, and perivascular fat), pancreatic fat, skeletal muscle fat, brown adipose tissue, and a dysbiotic gut that contribute to either T2DM or CVD. Arrows indicate changes in comparison with subjects without T2DM or CVD. The T2DM treatment strategies that have been reported to improve each adipose depot feature are listed under “treatments.” Treatments: weight loss due to lifestyle changes (L); weight loss due to bariatric surgery (B); metformin (M); GLP-1 receptor agonists (G); SGLT-2 inhibitors (S); thiazolidinediones (TZDs, T); anti-inflammatory approaches (AI); microbiome modulation with pre- or pro-biotics (P).