Effects Of Dietary Energy And Resveratrol Dose On Oxidative Stress And Lipid Metabolism In Mice

Objective: With the increase of dietary fat levels, both the body redox status and lipid metabolism were changed, which led to different levels of oxidative stress. Resveratrol(RSV) could relieve oxidative stress and maintain homeostasis within the inner environment. This study aimed to explore the effects of different energy levels of diets on redox status and lipid metabolism in mice and the preventive effect of RSV, to provide a theoretical basis for reasonable supplement of RSV and other antioxidants.Methods: Ninety C57BL/6J male mice were randomly divided into nine groups: low fat diet(LF, 5% fat) and in addition were given 0.01% RSV(LFL) or 0.02% RSV(LFH) respectively, medium fat diet(MF, 10% fat) and in addition were given 0.02% RSV(MFL) or 0.04% RSV(MFH) respectively, high fat diet(HF, 20% fat) and in addition were given 0.04%(HFL) or 0.08% RSV(HFH) respectively. Indirect calorimetry analysis was conducted on 8th and 17 th week. In the end of 17 th week, mice were sacrificed. The liver morphological analysis of histological sections was performed by microscopy. Visceral adipose tissue and liver index, plasma and hepatic lipids, hepatic redox status-related indicators were measured. Hepatic antioxidant and lipid metabolism-related genes expression as well as the expression of brown adipose tissue uncoupling protein genes were analyzed by RT-PCR.Results: With the increase of dietary fat contents, plasma TG, TC, ALT, AST and hepatic TG, TC, ROS, MDA levels were gradually increased. Hepatic SOD, GSH-Px levels were gradually decreased among LF, MF and HF groups(P<0.05). Compared with LF group, hepatic fatty acid oxidation and antioxidant genes were significantly down-regulated. Lipid synthesis-related genes were significantly up-regulated in MF and HF mice, and there were remarkably different expressions of Fas, SREBP1 c and PGC-1a gene(P<0.05). 0.02% RSV could significantly elevate plasma TG, TC levels and hepatic Fas, ACC gene expression, reduce hepatic SOD, CAT, GSH-Px and hepatic Fox O3 a, catalase gene expression in LF group(P<0.05). 0.04% RSV was more effective than 0.02% RSV in reducing plasma TG, TC, ALT and hepatic TG, TC levels, down-regulating SREBP1 c and its downstream lipid synthesis-related genes expression, up-regulating AMPK/SIRT1, Fox O3 a and their downstream genes expression, improving hepatic lipid metabolism and antioxidant capacity in MF group(P<0.05). 0.04%RSV had remarkable effects on the expression of lipid synthesis, fatty acid oxidation and antioxidant-related genes and could reduce plasma and hepatic lipids, improve hepatic antioxidant enzyme levels in HF mice(P<0.05). While 0.08% RSV had less effects than the dose of 0.04%. Indirect calorimetry analysis showed that, with the prolonging feeding time, VO2, RER and activity levels had reduced significantly in MF and HF group(P<0.05). In 17 th week, VO2, RER and night activity levels were gradually decreased among LF, MF and HF groups(P<0.05), while RSV treatment had no remarkable effects.Conclusion: With the increase of dietary fat, lipid metabolism disorder were occurred, which led to different degrees of oxidative stress in mice. 0.02% RSV could lead to a certain degree of pro-oxidation phenomenon in LF mice. 0.04%RSV were more effective than 0.02% RSV in restoring the body’s antioxidant capacity and improving dietary fat induced abnormal lipid metabolism in MF mice. 0.04% RSV could partially restore the antioxidant capacity and lipid metabolism in HF mice. Whereas, 0.08% RSV might play a pro-oxidant effect in the body, could not improve hepatic redox staus and lipid metabolism.