Article date: August 2016
By: Padmamalini Baskaran, Vivek Krishnan, Jun Ren, Baskaran Thyagarajan in Volume 173, Issue 15, pages 2369-2389
Background and Purpose
The 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 Approach
We 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 Results
Capsaicin 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 PPARγ 1 coactivator α and enhanced metabolic and ambulatory activity. Further, capsaicin stimulated sirtuin‐1‐dependent deacetylation of PPARγ and the transcription factor PRDM‐16 and facilitated PPARγ–PRDM‐16 interaction to induce browning of WAT. Dietary capsaicin did not protect TRPV1−/− mice from obesity.
Conclusions and Interpretations
Our 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.
DOI: 10.1111/bph.13514
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