Healthy versus Unhealthy Adipose Tissue Expansion: the Role of Exercise

Abstract

Although the hallmark of obesity is the expansion of adipose tissue, not all adipose tissue expansion is the same. Expansion of healthy adipose tissue is accompanied by adequate capillary angiogenesis and mitochondria-centered metabolic integrity, whereas expansion of unhealthy adipose tissue is associated with capillary and mitochondrial derangement, resulting in deposition of immune cells (M1-stage macrophages) and excess production of pro-inflammatory cytokines. Accumulation of these dysfunctional adipose tissues has been linked to the development of obesity comorbidities, such as type 2 diabetes, hypertension, dyslipidemia, and cardiovascular disease, which are leading causes of human mortality and morbidity in modern society. Mechanistically, vascular rarefaction and mitochondrial incompetency (for example, low mitochondrial content, fragmented mitochondria, defective mitochondrial respiratory function, and excess production of mitochondrial reactive oxygen species) are frequently observed in adipose tissue of obese patients. Recent studies have demonstrated that exercise is a potent behavioral intervention for preventing and reducing obesity and other metabolic diseases. However, our understanding of potential cellular mechanisms of exercise, which promote healthy adipose tissue expansion, is at the beginning stage. In this review, we hypothesize that exercise can induce unique physiological stimuli that can alter angiogenesis and mitochondrial remodeling in adipose tissues and ultimately promote the development and progression of healthy adipogenesis. We summarize recent reports on how regular exercise can impose differential processes that lead to the formation of either healthy or unhealthy adipose tissue and discuss key knowledge gaps that warrant future research.

Keywords: Adipose tissue; Angiogenesis; Exercise; Mitochondrion.

Figure 1

Schematic of the proposed mechanism. Excessive caloric intake and low energy expenditure create a positive energy balance, leading to adipose tissue expansion to store the excess energy. Adipose tissue can grow in size (hypertrophy) or in unit number (hyperplasia). Angiogenesis and mitochondrial remodeling are activated after exercise and act as signals for healthy adipose tissue expansion. Adipogenesis is the primary factor allowing hyperplasia to occur. Hyperplasia appears to preserve metabolic functions of the tissue. Hypertrophied adipose tissue is characterized by hypoxia, inflammation, fibrosis, and insulin insensitivity. When enough adipose tissue is dysfunctional, changes to adipokines, metabolites, and immune cells contribute to metabolic diseases such as diabetes, dyslipidemia, hypertension, and atherosclerosis. TNF-α, tumor necrosis factor alpha.