Tetrahydrocurcumin Ameliorates Skin Inflammation by Modulating Autophagy in High-Fat Diet-Induced Obese Mice

Obesity can induce chronic low-grade inflammation via oxidative stress. Tetrahydrocurcumin (THC) is a major curcumin metabolite with anti-inflammatory and antioxidant effects, but little is known about its effects on the skin of obese individuals. Thus, the aim of this study was to investigate the effects of THC on inflammatory cytokine production, oxidative stress, and autophagy in the skin of mice with high-fat diet- (HFD-) induced obesity. Eight-week-old C57BL/6J mice were fed a regular diet, HFD (60% of total calories from fat), or HFD supplemented with THC (100 mg/kg/day orally) for 12 weeks. We measured their body weights during the experimental period. After 12-week treatments, we performed western blotting and real-time polymerase chain reaction analyses on skin samples to evaluate the expression of inflammatory cytokines, oxidative stress markers, and autophagy markers. We observed higher tumor necrosis factor-α (TNF-α), NADPH oxidase 2 (Nox2), Nox4, and phosphorylated p65 levels; lower nuclear factor erythroid 2-related factor 2 (Nrf2) expression; and higher light chain 3 (LC3), autophagy-related 5 (Atg5), and Beclin 1 expression in the skin of HFD mice compared to the corresponding levels in the skin of mice fed with regular diet. THC administration decreased TNF-α, Nox2, Nox4, and phosphorylated p65 levels and activated the Nrf2 pathway. Interestingly, THC administration suppressed the expression of the autophagy markers LC3, Atg5, and Beclin 1. Overall, HFD-fed mice exhibited an elevation in inflammation, oxidative stress, and autophagy in their skin. THC ameliorated obesity-related skin pathology, and therefore, it is a potential therapeutic agent for obesity-related inflammatory skin diseases.