Capsaicin induces browning of white adipose tissue and counters obesity by activating TRPV1 channel-dependent mechanisms

Background and PurposeThe growing epidemic of obesity and metabolic diseases necessitates the development of novel strategies to prevent and treat such diseases. Current research suggests that browning of white adipose tissue (WAT) promotes energy expenditure to counter obesity. Recent research suggests that activation of the TRPV1 channels counters obesity. However, the mechanism by which activation of TRPV1 channels counters obesity still remains unclear. Experimental ApproachWe evaluated the effect of dietary capsaicin to induce a browning program in WAT by activating TRPV1 channels to prevent diet-induced obesity using wild-type and TRPV1(-/-) mouse models. We performed experiments using preadipocytes and fat pads from these mice. Key ResultsCapsaicin stimulated the expression of brown fat-specific thermogenic uncoupling protein-1 and bone morphogenetic protein-8b in WAT. Capsaicin triggered browning of WAT by promoting sirtuin-1 expression and activity via TRPV1 channel-dependent elevation of intracellular Ca2+ and phosphorylation of Ca2+/calmodulin-activated protein kinase II and AMP-activated kinase. Capsaicin increased the expression of PPAR 1 coactivator and enhanced metabolic and ambulatory activity. Further, capsaicin stimulated sirtuin-1-dependent deacetylation of PPAR and the transcription factor PRDM-16 and facilitated PPAR-PRDM-16 interaction to induce browning of WAT. Dietary capsaicin did not protect TRPV1(-/-) mice from obesity. Conclusions and InterpretationsOur results show for the first time that activation of TRPV1 channels by dietary capsaicin triggers browning of WAT to counteract obesity. Our results suggest that activation of TRPV1 channels is a promising strategy to counter obesity.