Unwiring the transcriptional heat circuit.

Abstract

Mature adipocytes are postmitotic (1), and therefore development of adipocytes requires the proliferation and differentiation of progenitor cells into mature adipocytes. The identity of adipose precursor cells and the molecular mechanisms that control their proliferation and differentiation are only partially understood. Brown adipose tissue (BAT) is specialized for energy expenditure through a process mediated by uncoupling protein 1 (UCP1) that uncouples respiration from ATP synthesis and generates heat (2). Current knowledge defines two types of thermogenic adipocytes based on their distinct origins, anatomical locations, and differential abilities to respond to stimuli. The classical brown adipocytes mainly develop during embryonic stage, form a discrete depot, and exert a high level of basal thermogenic capacity. The other type of brown fat-like cells, called beige or brite adipocytes, are dispersed in white adipose tissue (WAT) and are recruited and induced in response to certain stimuli. Although beige adipocytes also generate heat by UCP1-mediated proton leak, they arise from a myogenic factor 5-negative (Myf5−) developmental lineage distinct from brown adipocytes, which develop from Myf5+ progenitors (Fig. 1) (3, 4). Aside from the adrenergic pathways that activate thermogenesis in both brown and beige adipocytes, whether there exists a common factor that marks and specifies the fate of these thermo-competent cells remains unknown. In PNAS, Wang et al. (5) identify early B-cell factor 2 (Ebf2) as a marker that specifies the brown and beige adipocyte lineage from muscle, dermal, and white adipocyte lineages and provide new insight into transcriptional targets of Ebf2 that may play a role in activating the thermogenic gene program.