Biochemistry of adipose tissue: an endocrine organ

Abstract

Adipose tissue is no longer considered to be an inert tissue that stores fat. This tissue is capable of expanding to accommodate increased lipids through hypertrophy of existing adipocytes and by initiating differentiation of pre-adipocytes. Adipose tissue metabolism exerts an impact on whole-body metabolism. As an endocrine organ, adipose tissue is responsible for the synthesis and secretion of several hormones. These are active in a range of processes, such as control of nutritional intake (leptin, angiotensin), control of sensitivity to insulin and inflammatory process mediators (tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), resistin, visfatin, adiponectin, among others) and pathways (plasminogen activator inhibitor 1 (PAI-1) and acylation stimulating protein (ASP) for example). This paper reviews some of the biochemical and metabolic aspects of adipose tissue and its relationship to inflammatory disease and insulin resistance.

Keywords: adipocytes; adipokines; adipose tissue.

Figure 1

The most significant physiological functions of white adipose tissue such as coagulation, appetite regulation, immunity, glucose and lipid metabolism, reproduction, angiogenesis, fibrinolysis, body weight homeostasis and vascular tone control

Figure 2

Primary metabolic role of adipose tissue. In the feeding state, insulin-dependent glucose transport 4 (GLUT 4) allows the uptake of glucose from the bloodstream to adipocytes. Glycolysis occurs, producing glycerol-3-phosphate (glycerol-3-P), a substrate required for lipogenesis. Fatty acids from liver carried by very low-density lipoproteins (VLDL) and chylomicrons from the intestine are esterified with glycerol-3-P to form lipid droplets of triacylglycerols (TAGs). In the fasting state and in stress conditions, hormonesensitive lipase is activated for lipolysis. Some steps are required to produce glycerol, which travels to the liver, and fatty acids. These free fatty acids will tra vel in the bloodstream to the liver, muscle and to other organs to be oxidized. In the bloodstream fatty acids are immediately bound to albumin

Figure 3

Some of the factors secreted by white adipose tissue, which underlie the multifunctional nature of this endocrine organ: adiponectin, leptin, angio tensin, resistin, visfatin, acylation stimulating protein (ASP), sex steroids, glucocorticoids, tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), and free fatty acids (FFA), among others

Figure 4

The expansion of adipose tissue leads to adipocyte hypertrophy in obesity. The release of che mokines that induce recruitment of macrophages from the bloodstream increases infiltration and inflammation with enhanced production of pro-inflammatory cytokines such as tumor necrosis factor α (TNF-α) and IL-6. This is accomplished by increased release of FFA and dysregulated secretion of leptin, adiponectin and resistin. The macrophage and adipose tissue-derived adipokines acts in a paracrine or autocrine way, which exacerbates adipose tissue inflammation. Altered adipokine secretion, at the systemic level, can lead to decreased muscle and liver insulin sensitivity through enhanced ectopic lipid deposition and inflammation. These effects lead to increased liver glucose production (by means of gluconeogenesis and glycogenolysis). In contrast, muscle metabolism is reshuffled to a pattern of low glucose uptake and low FFA oxidation (with increases in levels of glycerol substrate for liver gluconeogenesis). These events lead to an increase of plasma glucose and, subsequently, an increase of insulin resistance. Adapted from: Galic S et al., 2010