Abstract
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.
Highlights
Obesity, a global health problem, is a major cause of systemic metabolic inflammation and various diseases, including type 2 diabetes, dyslipidemia, hypertension, and cardiovascular diseases [1]
tumor necrosis factor-α (TNF-α) mRNA expression was significantly higher in the HFD group mice than in the regular diet group mice
To determine the detailed mechanisms underlying the antiinflammatory and antioxidant effects of THC, we evaluated its effect on the nuclear factor- (NF-)κB/p65 expression. p65 mRNA expression and phosphorylated p65 protein levels in the skin of high-fat diet- (HFD-)fed mice were significantly higher than those in the skin of regular-diet-fed mice. p65 mRNA expression and phosphorylated p65 protein levels were significantly lower in the skin of HFD+T100-fed mice than in the skin of HFD-fed mice (Figure 5)
Summary
A global health problem, is a major cause of systemic metabolic inflammation and various diseases, including type 2 diabetes, dyslipidemia, hypertension, and cardiovascular diseases [1]. Obesity has been linked to various skin conditions, such as lymphedema, acanthosis nigricans, striae distensae, and psoriasis [2,3,4]. Obese individuals often experience reduced skin barrier function, dry skin, and itching [5]. The mechanisms underlying obesity-associated skin pathologies remain unclear. Autophagy is the primary process involved in the cellular elimination of toxic protein aggregates, damaged organelles, and invading microorganisms [6]. Autophagy can regulate the NF-κB signaling pathway and affect immune responses [7]. Autophagy plays an important protective function against obesity and obesity-induced lipotoxic, proteotoxic, and oxidative stresses
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