Abstract
Brown adipocytes are a specialized cell type that is critical for adaptive thermogenesis, energy homeostasis, and metabolism. In response to cold, both classical brown fat and the newly identified “beige” or “brite” cells are activated by β-adrenergic signaling and catabolize stored lipids and carbohydrates to produce heat via UCP1. Once thought to be non-existent in adults, recent studies have discovered active classical brown and beige fat cells in humans, thus reinvigorating interest in brown and beige adipocytes. This review will focus on the newly discovered transcription factors and microRNAs that specify and orchestrate the classical brown and beige fat cell development.
Highlights
Brown adipocytes are a specialized cell type that is critical for adaptive thermogenesis, energy homeostasis, and metabolism
Several studies have revealed that adult human brown adipose tissue (BAT) is more similar to the mouse beige cells [10, 20,21,22], while other studies showed that it is closer to the classical BAT [23, 24]
Knockdown of PRD1-BF-1-RIZ1 homologous-Domain Member 16 (PRDM16) in primary brown preadipocytes leads to myocyte differentiation and ectopic PRDM16 expression in myoblasts turns them into brown fat cells upon adipogenic stimulation [11]. These results suggest that PRDM16 controls a cell fate switch between brown fat and myocyte differentiation in bipotent progenitors
Summary
External adipogenic signals activate a cascade of core transcription factors that are critical for both brown and white adipocyte differentiation. Adipogenic stimulation of either white or brown preadipocytes leads to a sequential activation of core transcription factors [25, 28, 29] (Figure 1). One of the earliest activated transcription factors are CCAAT-enhancer-binding protein-β (CEBP-β) and CEBP-δ, which form a heterodimer and transcriptionally activate peroxisome proliferator-activated receptor γ (PPARγ), along with another family member, CEBP-α. PPARγ is a member of the nuclear hormone receptor superfamily and is the master regulator of adipogenesis as its sole expression is sufficient to convert fibroblasts into adipocytes [30]. Zfp423, which contains 30 Kruppel-like zinc fingers and a SMAD-binding domain, was identified as a regulator of preadipocyte determination by activating the transcription of PPARγ [31] (Figure 1). Deletion of Zfp423 in mice inhibits both brown and white adipogenesis
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