Brown Adipose Tissue, Thermogenesis, and Obesity: A Review of Literature

Abstract

The white adipose tissue (WAT) mass in adult humans ranges between 10-35 kg. The cells are normally sensitive to insulin in the fed state, and to glucagon and adrenaline in fasting or during exercise. Well-fed sedentary individuals are prone to weight gain as they fall victims to the anabolic mechanisms led mainly by insulin. Brown adipose tissue (BAT), by contrast, stores smaller amounts of triglycerides in multi-locular droplets, is highly vascularized and its cells are rich in unique mitochondria which are capable of uncoupling oxidation from phosphorylation or ATP formation. The tissue is innerved by the sympathetic nervous system and is highly sensitive to iodothyronines. It releases heat in the body in response to sympathetic activity. BAT unique mitochondria express numerous cristae and, unlike ordinary mitochondria on other body cells including WAT cells, they express uncoupling protein-1 (UCP-1, or thermogenin). UCP-1 allows the mitochondria to oxidize more fat and glucose as they escape the controlling mechanisms that depend on the coupling of oxidation to the demand for ATP, i.e., uncouples oxidative phosphorylation. Thermogenin (UCP-1) is a natural un-coupler of oxidative phosphorylation as it dissipates the proton gradient generated across the inner mitochondrial membrane, which is required to attain a certain level for the activation of ATP synthesis in mitochondrial matrix. In BAT, ATP synthesis is inhibited, as the protons are dissipated, and most energy is released as heat. The different proportions and activity of BAT and WAT in different individuals might explain why some people are more prone to weight gain, and find it difficult to lose weight, than others; and also explains the tendency for weight gain as individuals get older. New approaches in the battle against obesity, metabolic syndrome and type 2 diabetes mellitus are expected through better understanding of how this balance between WAT and BAT is controlled. Interestingly, long term adrenergic stimulation of WAT induces browning of some white adipocytes, and the tissue gradually turns into & quot; beige & quot; adipose tissue, which shares characteristics of brown adipose tissue like thermogenesis, larger number of mitochondria and smaller lipid droplets, all developing in a gradual way. The adipose tissue interconverts its cell types in order to adapt for the changing metabolic balance and other stimuli. This phenomenon is currently incompletely understood, albeit significant for our understanding of obesity, metabolic syndrome and type 2 diabetes mellitus and many consequent complications of insulin resistance. Moreover, the nervous system is involved in the regulation of WAT and BAT through effects on fat cell proliferation, differentiation, trans-differentiation and apoptosis. The brain interacts with different adipocytes and adipokines in the pathogenesis of obesity, type 2 diabetes mellitus, anorexia, cachexia and other syndromes. This review will target many of these aspects in an attempt to draw more attention in the direction of this major health issue.