Cold exposure induces nuclear translocation of CRTC3 in brown adipose tissue.

Abstract

In mammals, cold stress activates the cAMP-protein kinase A (PKA) signaling pathway, increases brown adipose tissue (BAT) activity, and induces thermogenesis to maintain body temperature. The cAMP responsive element binding protein (CREB)-regulated transcription coactivator 3 (CRTC3) plays important role in adipose development and energy metabolism. However, the effect of cold exposure on the intracellular localization of CRTC3 in BAT is unclear. Here, we report that cold-treated mice have higher expression of uncoupling protein 1 (UCP1) in adipose tissues and lower body weights and fat masses. Notably, cold exposure results in the nuclear translocation of CRTC3 in BAT. Moreover, forskolin (FSK), the activator of PKA pathway, induces the nuclear translocation of CRTC3 in brown adipocytes. At the molecular level, cold exposure and FSK treatment decrease liver kinase B1 (Lkb1) expression in brown adipocytes, which is related to the nuclear localization of CRTC3. These results demonstrate that the localization of CRTC3 involves in regulating cold-induced upregulation of UCP1 in BAT and provide useful information for understanding the molecular regulation of BAT thermogenesis induced by a cold environment.