Regulatory circuits controlling white versus brown adipocyte differentiation

Abstract

Adipose tissue is a major endocrine organ that exerts a profound influence on whole-body homoeostasis. Two types of adipose tissue exist in mammals: WAT (white adipose tissue) and BAT (brown adipose tissue). WAT stores energy and is the largest energy reserve in mammals, whereas BAT, expressing UCP1 (uncoupling protein 1), can dissipate energy through adaptive thermogenesis. In rodents, ample evidence supports BAT as an organ counteracting obesity, whereas less is known about the presence and significance of BAT in humans. Despite the different functions of white and brown adipocytes, knowledge of factors differentially influencing the formation of white and brown fat cells is sparse. Here we summarize recent progress in the molecular understanding of white versus brown adipocyte differentiation, including novel insights into transcriptional and signal transduction pathways. Since expression of UCP1 is the hallmark of BAT and a key factor determining energy expenditure, we also review conditions associated with enhanced energy expenditure and UCP1 expression in WAT that may provide information on processes involved in brown adipocyte differentiation.

Figure 1. Molecular determinants involved in white versus brown adipocyte differentiation

Factors that characterize white or brown adipogenesis are indicated in the upper and middle parts of the Figure respectively, whereas factors influencing PGC-1α activity at various levels are listed in the lower part. The mechanism by which LXR affects UCP1 expression in fat and white versus brown adipose conversion is unknown. The potential transdifferentiation of white and brown fat cells is indicated in the upper right part of the Figure. See the text for details. The involvement of TRAP220 and PGC-2 in white adipose conversion has been described [219,220].