Perivascular Fat and the Microcirculation: Relevance to Insulin Resistance, Diabetes, and Cardiovascular Disease

Abstract

Type 2 diabetes and its major risk factor, obesity, are a growing burden for public health. The mechanisms that connect obesity and its related disorders, such as insulin resistance, type 2 diabetes, and hypertension, are still undefined. Microvascular dysfunction may be a pathophysiologic link between insulin resistance and hypertension in obesity. Many studies have shown that adipose tissue-derived substances (adipokines) interact with (micro)vascular function and influence insulin sensitivity. In the past, research focused on adipokines from perivascular adipose tissue (PVAT). In this review, we focus on the interactions between adipokines, predominantly from PVAT, and microvascular function in relation to the development of insulin resistance, diabetes, and cardiovascular disease.

Fig. 1

The postulated pathophysiologic framework underlying the hypothesis that microvascular dysfunction links hypertension and insulin resistance. ACE—angiotensin-converting enzyme; ARB—angiotensin II receptor blocker; RAS—renin-angiotensin system; TNFα—tumor necrosis factor α. (Adapted from Jonk [90].)

Fig. 2

Products of perivascular adipose tissue involved in regulation of (micro)vascular function. Depicted is perivascular adipose tissue in a biopsy taken from the quadriceps muscle of a type 2 diabetic patient. The black arrow indicates a microvessel. ADRF—adventitia-derived relaxing factor; Ang II—angiotensin II; Ang (1–7)—angiotensin (1–7); FABP4—fatty acid-binding protein 4; H₂S—hydrogen sulphate; IL—interleukin-; MCP-1—monocyte chemoattractant protein-1; MIP-1α—macrophage inflammatory protein-1α; ROS—reactive oxygen species; TNFα—tumor necrosis factor α