Capsaicin Mitigates Reverbα-Involved Lipid Metabolism Disorder in HepG2 Cells and Obese Mice through a Trpv1-Dependent Mechanism

Capsaicin (CAP), the active component of chili peppers, exerts a range of health benefits, including anti-inflammatory, antitumor, obesity-prevention, metabolic control, and biological rhythm-modulating effects, primarily through the activation of the transient receptor potential vanilloid 1 (TRPV1) receptor. The research explores the role of TRPV1 and its interaction with hepatic circadian clock regulation in modulating lipid metabolism and liver health. The effect of CAP on lipid metabolism and the potential mechanism was examined in HepG2 cells and high-fat, high-sugar diet (HFFD)-induced obese mice. In vitro, CAP (50 μM) decreased lipid droplet overaccumulation (from 152.8 ± 2.30 to 110.13 ± 3.91%), enhanced mitochondrial function (from 57.94 ± 1.93 to 86.74 ± 1.83%), and alleviated circadian desynchrony through a Trpv1-dependent mechanism in HepG2 cells. In vivo, CAP (5 mg/kg) reduced the body weight gain (from 50.61 ± 3.77 to 38.36 ± 2.04%), restored the hepatic circadian rhythm, and modulated the expression of lipid-related genes through the involvement of TRPV1 in mice. This study highlighted the potential of CAP to attenuate Reverbα-mediated lipid metabolic dysfunction through a Trpv1-dependent mechanism, revealing a complex interplay between circadian regulation and lipid metabolism.