Resveratrol prevents suppression of regulatory T-cell production, oxidative stress, and inflammation of mice prone or resistant to high-fat diet-induced obesity

Abstract

Consumption of a high-fat diet (HFD) is correlated with increased oxidative stress and chronic inflammation in many organs. Regulatory T cells (Tregs) are essential negative regulators of inflammation. We hypothesized that resveratrol (trans-3,5,4'-trihydroxystilbene) could protect against HFD-induced oxidative stress and inflammation. Therefore, we examined the effect of resveratrol on oxidative stress and the relevant peripheral immune-regulating mechanisms in HFD-induced obese (DIO) and diet-resistant mice. C57BL/6 mice were fed a normal diet and an HFD for 13 weeks. Then the experimental group was subdivided into DIO and diet-resistant groups according to their body weights, which were further supplemented with 0.03% resveratrol and 0.06% resveratrol, respectively, for an additional 13 weeks. Resveratrol prevented the accumulation of chronic oxidative stress and suppression of Tregs production in HFD mice, modulated changes of cytokines in the plasma and spleen, and decreased expressions of inflammatory mediators compared with those of the DIO group. Our results indicate that resveratrol, as a feasible effective supplement for HFD, can relieve oxidative stress, inhibit inflammatory genes expression, and increase Tregs number via aryl hydrocarbon receptor activation inhibited by HFD, especially in DIO mice.

Keywords: AhR; CAT; CTLA-4; CYP1A1; DIO; DR; ELISA; FoxP3; GSH-Px; GSH/GSSG; HFD; High-fat diet–induced obesity; IL-1; Il7r; Inflammation; MCP-1; MDA; MMP-9; Mice; NAD(P)H dehydrogenase [quinone 1]; NF-κB; NQO1; Oxidative stress; PBMCs; PPARγ; QRT-PCR; Regulatory T cells; Resveratrol; TAC; TGF-β; TNF-α; Tregs; UDP glucuronosyltransferase 1A1; UGT1A1; aryl hydrocarbon receptor; catalase; cytochrome P450 1A1; cytotoxic T lymphocyte–associated antigen-4; diet resistant; enzyme-linked immunosorbent assay; forkhead box P3; glutathione peroxidase; glutathione/glutathione disulfide; high-fat diet; high-fat diet–induced obese; interleukin 1; interleukin-7 receptor; mAbs; mRNA; malondialdehyde; matrix metallopeptidase 9; messenger RNA; monoclonal antibodies; monocyte chemotactic protein-1; nuclear factor κB; peripheral blood mononuclear cells; peroxisome proliferator–activated receptor γ; quantitative real-time reverse transcription polymerase chain reaction; regulatory T cells; total antioxidant capacity; transforming growth factor β; tumor necrosis factor α.