Regulatory Mechanisms of Capsaicin in Ucp1-Involved Thermogenic Biorhythm in Mouse Brown Adipose Tissue and C3H10T1/2 Cell Differentiation

Obesity and metabolic disorders are significant global health challenges, contributing to the prevalence of numerous chronic diseases. Capsaicin (CAP) has demonstrated the ability to promote the browning of white adipose tissue (WAT) and enhance thermogenesis in brown adipose tissue (BAT), thereby maintaining energy homeostasis primarily through uncoupling protein 1 (UCP1)-mediated thermogenesis. The thermogenic function of BAT is regulated by circadian rhythms, and disruptions in these rhythms may contribute to metabolic dysfunctions and obesity. However, the effects of CAP on the circadian regulation of BAT thermogenesis remain unclear. This study investigates the effect of CAP on circadian thermogenesis in BAT and its potential to counteract obesity induced by a high-fat, high-fructose diet (HFFD) in murine and cell models. The results demonstrated that CAP significantly reduced weight gain and adiposity, preserved the thermogenic capacity of BAT, and restored the circadian rhythms of key thermogenic genes in BAT. CAP also promoted the differentiation of C3H10T1/2 mesenchymal stem cells into brown adipocytes and enhanced mitochondrial function by mitigating oxidative stress and improving mitochondrial membrane potential through a circadian involvement mechanism. These findings highlight CAP as a promising therapeutic agent for regulating energy expenditure and preventing obesity-related metabolic disorders.