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

Abstract

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 dietinduced obesity using wild-type and TRPV1 À/À 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 protein8b in WAT. Capsaicin triggered browning of WAT by promoting sirtuin-1 expression and activity via TRPV1 channel-dependent elevation of intracellular Ca 2+ and phosphorylation of Ca 2+ /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 À/À 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. IntroductionObesity is the hallmark of metabolic syndrome (Maestu et al., 2010). It foreshadows type II diabetes, dyslipidemia, vascular anomalies and the overall risk of cardiovascular diseases (Arya et al., 2002). Decreased physical activity coupled with increased high-fat diet (HFD) intake prompts obesity (Yagi et al., 2014). Effective clinical management is still lacking to combat obesity. Recent studies indicate that high fructose in a diet is a critical factor leading to obesity as the combination of sugars and refined carbohydrates along with fat lead to metabolic syndrome Lucan and DiNicolantonio, 2015). Recent evidence suggests that browning of white adipose tissue (WAT) might serve as a novel strategy to improve metabolic health (Bartelt and Heeren, 2014). WAT stores energy in the form of fat, while brown adipocytes promote energy expenditure via thermogenesis by burning fat. Browning of WAT favours the energy expenditure by triggering thermogenesis, which suppresses diet-induced weight gain (Cao et al., 2011;Bordicchia et al., 2012;Bi et al., 2014). Further analysis of molecular mechanisms underscoring induction of browning of WAT led to identification of adipogenic factors, their stabilization and interaction with proteins, which serve as catalysts for browning of WAT (Ohno et al., 2012;Qia...

TRPV1 activation counters diet-induced obesity through sirtuin-1 activation and PRDM-16 deacetylation in brown adipose tissue

“…We have previously reported that TRPV1 activation caused beiging of inguinal WAT 9 . This report provides evidence for the expression of TRPV1 protein in BAT and demonstrates that CAP counters diet-induced obesity by activating TRPV1 in BAT.…”

Role of Thermo-Sensitive Transient Receptor Potential Channels in Brown Adipose Tissue

“…58,63,64) Because it would be difficult for dietary intake of capsaicin directly to activate TRPV1 expressed in adipose tissue, these phenotypes might be caused via mechanisms other than TRPV1 expression in adipose tissue. Rather, TRPV1 expressed in peripheral sensory neurons derived from the nodose ganglion is more important for controlling energy metabolism (see also references from Saito et al 65) and Uchida et al…”

Phytochemicals as novel agents for the induction of browning in white adipose tissue

“…The effect of capsaicin/capsinoid treatment has been compared to that of chronic cold exposure, in which sympathetic stimulation results in the activation of BAT [87]. Similarly to the aforementioned curcumin, capsaicin binds to the intestinal transient receptor potential vanilloid 1(TRPV1) receptor, also referred to as the capsaicin receptor, thereby launching the sympathetic response observed with treatment [89]. Surprisingly, capsaicin has also been proven to be harmful to humans and these harmful effects are mediated, in part, by the capsaicin receptor, TRPV1 [90–92].…”