Resveratrol ameliorates chronic high altitude exposure-induced oxidative stress and suppresses lipid metabolism alteration in rats

High altitude affects energy metabolism. Resveratrol is the natural compound that activates sirtuins, which produce beneficial effects on lipid metabolism. The study was conducted to investigate the role of resveratrol in lipid metabolism of rats exposed to a high altitude hypoxia environment. Sprague-Dawley rats were divided into control, resveratrol (30mg/kg B.W./d) (Res), high altitude hypoxia (HH), and high altitude hypoxia+resveratrol (30mg/kg B.W./d) (HH+Res) groups. Rats in HH and HH+Res groups were placed in a hypobaric chamber at a stimulated elevation of 4500m for 30 days. Plasma lipid profile, antioxidant indexes, key enzyme activities, lipid metabolism-related genes, and hypoxia-inducible factors (HIFs) expression were evaluated. Results showed that resveratrol alleviated hypobaric hypoxia-induced enlargement of lung and spleen, and decreased serum malondialdehyde (MDA), plasma high density lipoprotein (HDL) and cholesterol (CHOL) contents, increased liver superoxide dismutase (SOD) activity and Sirtuin 1 (Sirt-1) expression levels, and decreased liver MDA and triglyceride (TG) levels compared to the HH group. Moreover, resveratrol increased fat hormone sensitive lipase (HSL) activity, and suppressed fat Acetyl-CoA carboxylase (ACC), Carnitine palmitoyltransferase (CPT-I) and fatty acid synthetase (FAS) activity. In addition, resveratrol decreased liver CCAAT/enhancer binding protein alpha (C/EBPα), peroxisome proliferator-activated receptor γ (PPARγ), and hypoxia inducible factor-1 alpha and hypoxia inducible factor-2 alpha (HIF-1α and HIF-2α) expression levels compared to the HH group. In conclusion, resveratrol can effectively ameliorate high altitude hypoxia-induced oxidative stress and alteration of lipid metabolism, which is associated with the HIF signaling pathway. Practical applications: Resveratrol may be a feasible agent for ameliorating high altitude-induced oxidative stress and lipid metabolism dysfunction. Moreover, the HIF-mediated alterations in genes involved in fat metabolism (Srit1, C/EBPα, and PPARγ) may be targets to prevent and treat lipid metabolic disease under a high altitude hypoxia environment.