Obesity-Induced Changes in Adipose Tissue Microenvironment and Their Impact on Cardiovascular Disease

Abstract

Obesity is causally linked with the development of cardiovascular disorders. Accumulating evidence indicates that cardiovascular disease is the collateral damage of obesity-driven adipose tissue dysfunction that promotes a chronic inflammatory state within the organism. Adipose tissues secrete bioactive substances, referred to as adipokines, which largely function as modulators of inflammation. The microenvironment of adipose tissue will affect the adipokine secretome, having actions on remote tissues. Obesity typically leads to the upregulation of proinflammatory adipokines and the downregulation of anti-inflammatory adipokines, thereby contributing to the pathogenesis of cardiovascular diseases. In this review, we focus on the microenvironment of adipose tissue and how it influences cardiovascular disorders, including atherosclerosis and ischemic heart diseases, through the systemic actions of adipokines.

Keywords: adipokines; adipose tissue; atherosclerosis; myocardial infarction; obesity.

Figure 1

Adipose tissue depots occur throughout the body. Studies suggest that visceral adipose tissue accumulation is a major risk factor for cardio-metabolic disease, whereas subcutaneous fat appears to be neutral or protective. Other adipose tissue depots of note include the epicardium, the perivascular space, and bone marrow, but the functional significance of these tissues is largely unknown. Brown adipose tissue occurs in the supraclavicular and paraspinal regions. In contrast to white adipose tissue, brown adipose tissue is very metabolically active and it functions to utilize fuel to produce heat. In addition, ectopic lipid can accumulate in tissues, such as liver, in metabolically dysfunctional organisms.

Figure 2

Functional adipose tissue (left), predominantly found in lean organisms, tends to express anti-inflammatory adipokines that protect against cardiovascular disease. In contrast, excess adipose tissue expansion promotes dysfunction (right), leading to the expression of pro-inflammatory adipokines that promote cardiovascular disease. Dysfunctional adipose tissue is characterized by enlarged adipocytes, vascular rarefaction, increased inflammatory cell infiltrate and the appearance of crown-like structures.

Figure 3

Obesity leads to adipose tissue dysfunction, triggering the release of pro-inflammatory adipokines which can directly act on cardiovascular tissues to promote disease. The adipokine imbalance can also affect the function of metabolically important tissues and the microvasculature, promoting insulin resistance and indirectly contributing to CVD.

Figure 4

Selected anti- and pro-inflammatory adipokines with summaries of their regulation and actions in the cardiovascular system.