Mechanisms of Anti-Obesity Effects of Capsaicin

Obesity is a major metabolic disease. Currently, there are no effective strategies to counter obesity. Transient receptor potential vanilloid subfamily 1 (TRPV1), a non-selective cation channel protein expressed in metablically important tissues, has been pursued as a target to combat obesity. In our efforts to understand the mechanisms by which activation of TRPV1 by its selective agonist capsaicin counters obesity we discovered that mammalian white and brown adipose tissues (WAT and BAT, respectively)  endgenously express TRPV1 protein. Feeding a high fat diet suppressed the expression of TRPV1 in both WAT and BAT. Feeding capsaicin along with high fat diet countered this, prevented obesity and promoted weight loss by 1). triggering the conversion of WAT to beige like phenotype, which expresses enhanced thermogenic UCP-1 and BMP compared to WAT. 2). enhancing thermogenesis in BAT and suppressing high fat diet-induced hypertension, hyperlipidemia and glucose intolerance. Also, capsaicin stimulates the deacetylation and interaction of PPAR gamma and PRDM-16 in both WAT and BAT by activating the metabolic sensor sirtuin-1. Further studies analyzing the molecular mechanisms underlying these processes and developing TRPV1 agonists as novel anti-obesity agents are in progress.