| Objectives: High-fat diet is an important inducement of the metabolic syndrome( MS), and the disorder of lipid metabolism is one of the characteristics of MS. On the other hand, resveratrol plays an important role in regulating lipid metabolism disorder. The thesis aimed to explore the effects and possible mechanisms of resveratrol on lipid metabolism, hormones of energy metabolism and biological rhythms in high-fat diet-fed mice, and to provide the theoretical base of prevention and treatment of resveratrol on lipid metabolism disorder induced by high-fat diet.Methods:Male C57BL/6 mice were divided into three groups: a standard diet control group( CON, 10% energy from fat), a high-fat diet( HFD, 45% energy from fat) group and HFD supplemented with 0.1%( w/w) resveratrol( RES) group. Body weight was monitored weekly, whole body metabolic status were monitored by Comprehensive Laboratory Animal Monitoring System after every two weeks. In the 11 week, all mice were randomly divided into 4 time points( 8:00, 14:00, 20:00 and 2:00) and sacrificed after 8 h fasting respectively. Blood, liver and adipose tissue were dissected. Lipid profile, fat content and energy metabolism related hormones were determined and redox state of fat and liver tissue were tested respectively, and all of these indexes were cosine fitting analyzed by the cosinor summary. Meanwhile, hepatic histology analysis was conducted, the expressions of lipogenesis, decomposition and oxidation related genes, as well as the clock and its upstream and downstream related genes in liver were determined by q PCR. Finally, the rhythm pattern was analyzed.Results:The circadian rhythms of respiratory exchange ratio( RER) and locomotor activity were disordered in HFD mice in the 2nd week, but the body weight reached significance at the 5th week and was 1.2 fold higher than control group, indicating that metabolism rhythm disorder exceeded the occurrence of obesity. Resveratrol supplementation attenuated RER and ambulatory activity circadian rhythm and reduced body weight significantly( P<0.05). In the 11 th week when biological rhythm and body weight were interrupted in HFD mice, all the mice were sacrificed, biological parameters, haematological indexes and gene expression were used to conduct rhythm analysis. Compared to control mice, the ratio of GSH/GSSG and T-SOD levels were significantly decreased. MDA levels were remarkably increased in liver and fat tissue of HFD mice. Furthermore, rhythmic expression disappeared or delayed. HFD group had significantly increased plasma insulin, leptin, free T3 and corticosterone levels in relative to control mice, all of which lost rhythmic expression. Correlation analysis demonstrated that energy metabolism related hormones levels were significantly correlated to plasma lipid profiles. Meanwhile, the expression of clock genes Clock, Bmall, Per2 and its downstream gene sirt1 were significantly down-regulated. The upstream gene Pparα and its target genes Srebp-1c, Acc1 and Fas were significantly up-regulated, Hsl and Acox1 were significantly downregulated, all the rhythmic expressions of these genes disappeared or delayed. Resveratrol could attenuate the clock expression and oxidative stress induced by HFD, improve energy metabolism related hormones levels and their rhythm, alter the rhythmic expression of lipid metabolism, and ultimately reduce body weight in mice.Conclusions:High-fat diet induced redox imbalance, destroyed the normal expression of clock genes in peripheral tissues, led to interruption of rhythmic expression of circulating energy metabolism related hormone and lipid metabolism genes, which might be the possible mechanism for lipid metabolism rhythm disorder. Resveratrol attenuated energy metabolism related hormones levels and rhythmic expression of lipogenesis, decomposition and oxidation related genes to improve lipid metabolism rhythm disorder induced by HFD via activating Sirt1 to regulate the expression of clock genes. |
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