Dietary capsaicin upregulates uncoupling protein 2/3 expression in visceral adipose tissue and enhances acetylcholine-induced hypotensive effect in mice

Obesity and hypertension are major risk factors for cardiovascular events. Some plant-based diets lower the prevalence of hypertension and prevent weight gain. Capsaicin, a major pungent ingredient in chili pepper, can specifically activate transient receptor potential vanilloid type-1 (TRPV1) channel. Our previous studies demonstrated that activation of TRPV1 channel by dietary capsaicin prevents adipogenesis and obesity in mice. However, little is known about the mechanism of TRPV1 activation mediated the reduction of adipogenesis and prevention of obesity. Furthermore, it is unclear whether long term dietary capsaicin could modulate blood pressure. Here, we report that capsaicin significantly increased the uncoupling proteins (UCP2 and UCP3) expression in mature adipocytes which indicated that capsaicin promoted the fat oxidation. Mice on high-fat diet (HFD) for 4 months developed obesity and increased UCP2 and UCP3 expression in visceral fat. Dietary capsaicin markedly prevented the development of obesity and further increased UCP2 and UCP3 expression in visceral fat from mice on HFD. Chronic administration of capsaicin also dose-dependently increased the acetylcholine-mediated hypotensive responses in mice, however, this effect was absent in TRPV1 deficient mice. We conclude that TRPV1 activation by dietary capsaicin increased fat oxidation and promoted hypotensive effects in mice. Dietary capsaicin may become a novel therapeutic strategy for obesity and its related cardiometabolic diseases.