Study On The Ameliorative Effects Of Resveratrol And Quercetin On Thyroid Hormones Function In Obese Mice Induced By High-fat Diet

Objectives: To 27 weeks, high fat diet induced obese mice, The present study aimed to find the periodic change of thyroid hormones level and of liver partial deiodinase1 and hormone receptor, by antioxidant intervention, to explore Whether the combination of resveratrol and quercetin had a more advantage on liver oxidative damage, abnormal secretion of thyroid hormone(TH)and energy metabolism, for the further study of chronic disease mechanisms, then provide the theoretical basis of prevention.Methods: 200 Male C57BL/6 Mice were fed with standard diet chow and provided tap water ad libitum for a 1 week acclimation period, randomly divided into 5 groups: a standard diet control group(Control), high fat diet group(HFD), quercetin(Que) group fed with HFD and supplemented with 0.1% quercetin(1 g/kg diet),(Rsv) group fed with HFD and supplemented with 0.1% resveratrol(1g/kg diet); combined quercetin and resveratrol(R+Q) group fed with HFD and supplemented with 0.05% quercetin and 0.05% resveratrol(0.5 g quercetin + 0.5 g resveratrol Per kg diet); mice were sacrificed at 3rd 、7th、17th、27th weeks, before sacrificed Indirect calorimetry was Performed. Plasma lipid Profiles, T3 target genes FAS, ACC1, CYP7A1(lipid metabolism genes)were analyzed by RT-PCR; thyroid stimulating hormone(TSH), thyroxine(T4), triiodothyronine(T3) were measured, liver deiodinase, thyroid hormone receptor analyzed by RT-PCR and western bolt; the expression level of mi RNA-224 and mi RNA-34 a analyzed by RT-PCR in liver tissue; oxidative stress markers were measured.Results: 1) after 7 weeks, compared with group control, HFD mice body weight, abdominal fat membrane fat, testosterone significantly elevated(P < 0.05), and continue to 27 weeks; 2) 7 and 27 weeks CLAMS metabolic system analysis results show that high-fat diets mice RER values were significantly lower than the control group, with energy intake increased significantly(P < 0.05), the energy expenditure decreased significantly(P <0.05); 3) from 7 to 27 weeks obes mice had more serious hepatic steatosis, serum triglyceride, cholesterol, LDL-C was significantly higher than control group, but HDL-C were significantly reduced, the liver TG and TC were significantly higher than control group, compared with control mice, T3 target genes(e.g. Acc1, Fas) involved in lipid synthesis is up-regualtion and Pgc1α, Cy P7a1 and CPt1α are down-regulation; 4) 7 to 17 weeks, in HFD group mice, TSH, T4 level was significantly higher than control group(P < 0.05), T3 level with no difference, compared with the control group, to 27 weeks, in HFD mice TSH levels increased significantly, T3 levels decreased significantly, but there is no difference with total T4; in the early high fat diet intervention, liver D1 and TRβ1 is significantly higher than control group(P < 0.05), from 17 weeks to 27 weeks HFD group D1 and TRβ1 expression was significantly lower than control group(P < 0.05). 5) at 7 weeks Mi RNA224 of HFD mice was significantly lower than control group, to 27 weeks mi RNA224 expression quantity increases significantly, 7 and 27 weeks mi RNA34 a is significantly higher than control group(P<0.05); 6) oxidative stress happened with a high-fat diet, MDA significantly increased, GSH/GSSG, SOD, T-AOC level were significantly decreased; 7) Resveratrol and quercetin can effectively alleviate the high fat body caused by oxidative stress, by enhancing the activity of D1 then regulated serum T3 levels, improve the TRβ1 protein expression and its T3 target genes m RNA level, promote energy metabolism, thus reducing body weight, and to keep the normal blood lipid levels, which in the early days, difference of resveratrol, quercetin and R+Q group is not obvious, but for long time, R+Q group has a certain advantage.Conclusion: High fat-diet can regulate mi RNA-224 mi RNA-34 a levels and decrease liver D1 and TRβ1 levels, led to the thyroid hormone disorder(T3), genes related lipid metabolism and plasma lipids abnormal. Resveratrol and quercetin can reduce the negative influence of high fat diet in varying degrees, but for Long-term HFD feeding combined supplementation with quercetin and resveratrol was more efficacious.