Brown Fat and Browning for the Treatment of Obesity and Related Metabolic Disorders

Abstract

Brown fat is a specialized fat depot that can increase energy expenditure and produce heat. After the recent discovery of the presence of active brown fat in human adults and novel transcription factors controlling brown adipocyte differentiation, the field of the study of brown fat has gained great interest and is rapidly growing. Brown fat expansion and/or activation results in increased energy expenditure and a negative energy balance in mice and limits weight gain. Brown fat is also able to utilize blood glucose and lipid and results in improved glucose metabolism and blood lipid independent of weight loss. Prolonged cold exposure and beta adrenergic agonists can induce browning of white adipose tissue. The inducible brown adipocyte, beige adipocyte evolving by thermogenic activation of white adipose tissue have different origin and molecular signature from classical brown adipocytes but share the characteristics of high mitochondria content, UCP1 expression and thermogenic capacity when activated. Increasing browning may also be an efficient way to increase whole brown fat activity. Recent human studies have shown possibilities that findings in mice can be reproduced in human, making brown fat a good candidate organ to treat obesity and its related disorders.

Keywords: Adipocytes, brown; Adipose tissue, brown; Beige adipocyte; Obesity.

Fig. 1. Brown adipose tissue (BAT) targeted treatment of obesity and related metabolic disorders. Increasing BAT amount and/or BAT activity leads to increased activation of uncoupling protein 1 (UCP1) and thermogenesis leading to energy expenditure which will have anti-obesity effects. On the other hand, BAT can also increase the uptake of blood glucose and lipid. Glucose and fatty acids are oxidized or stored as glycogen or triglyceride. This results in decrease in blood glucose and lipid and increase in insulin sensitivity, leading to anti-diabetic and anti-dyslipidemic effects.