Fig. 1 |. The biogenesis of beige fat.

In response to cold stimuli, norepinephrine is released from the sympathetic nerve endings and binds to β3-AR, which leads to increased levels of intracellular cAMP and subsequent activation of signaling via the kinase PKA and the mitogen-activated protein kinase p38. p38 phosphorylates transcriptional co-regulators, such as PGC1α, and promotes the expression of thermogenic genes (Ucp1, Cidea and Cox8b) and mitochondrial biogenesis. In the nucleus, Naap10 and GCN5 inhibit the transcriptional activity of PGC1α through N-terminal acetylation and lysine acetylation, respectively. The deacetylase SIRT1 removes the acetylation on PGC1α catalyzed by GCN5⁷. The N-terminal deacetylase remains unknown. Yellow ovals indicate lipid droplets.