Figure 2.

Molecular players in brown adipocyte development and function. Brown adipogenic differentiation involves multiple transcriptional regulators, with PRDM16, PPRAγ and PGC1α acting as main molecular players. PPARγ is the master transcription factor in adipogenic differentiation, whose association with PRDM16 and PGC1α initiates selective induction of brown adipogenic and thermogenic gene expression. Acetylation of PPARγ and phosphorylation of PGC1α increase the activity of these transcriptional complexes. Several binding partners of PRDM16 have been identified (CCAAT/enhancer-binding protein beta, PPARγ, early B cell factor-2, euchromatic histone-lysine N-methyltransferase 1 and C-terminal-binding protein) that are involved in mediating the expression of brown adipogenic genes and suppressing the expression of myogenic and white adipogenic genes. Upon sympathetic stimulation, catecholamines (for example, norepinephrine) induce thermogenic gene expression and lipolysis mainly through ADRB-cAMP-PKA signaling. Non-canonical stimulators (for example, natriuretic peptide, BMPs, fibroblast growth factor 21) have also been identified that have critical roles in BAT development and in the browning of WAT (see text for details; main references include).^{46, 70, 95}