| Objective: The feed intake, nutrient digestion rate, redox state, blood glucose, blood lipid,adipocytokines,and the differences of liver genes expression of obesity resistance(DIO-R),medium-weight(Med) and obese(DIO) mice were researched individual to reveal themechanism of obesity.2) The effects of different doses of resveratrol(RSV) on physiologystate of different weights were researched, which provided a theoretical basis for thedevelopment of the prevention of high-fat diet caused obesity and nutritional means tooxidative stress.Methods:The male mice of KM were fed with high-fat diet (HFD) for12weeks and weredivided into three kinds according to the body weight, such as DIO-R, Med and DIO. Eachtype of mice were divided into three groups, and each group were fed with the HFD, theHFD+0.3g/kgRSV and the HFD+0.6g/kgRSV diet for18weeks taking normal diet fed miceas control. Digestion experiments had been taken one week before the mice killed. After that,the body weight of mice,the weight of wet liver, epididymal white adipose tissue wet weight,perirenal white adipose tissue wet weight, abdominal fat rate, the CAT activity, MDA contentand other oxidation-reduction indicators of blood, liver, and adipose tissue, blood glucose,plasma TG,TCH,LDL-C,HDL-C and other blood fat biochemical indicators, IL-6, TNF-α,resistin, ADP and other levels of adipocytokines, levels of plasma leptin and insulin weretested. HE sections of adipose tissue pathology observation, liver gene chip expressionanalysis, the specific genes of RT-PCR verification on chip were proceeded at the same time.Results:1) Comparison of feed intake and nutrient digestion rate: compared with controlgroup, the feed intake decreased significantly but the digestibility of dry matter and crudeprotein significantly enhanced in the DIO-R HFD group; the digestibility of dry matter andcrude protein decreased significantly in the DIO HFD group. The digestibility of crude fatdecreased significantly in each HFD group(P<0.05).The treatment with RSV significantlydecreased the digestibility of dry matters, crude protein but increased crude fat.2)Comparison of the redox state and the inflammatory state between HFD group and controlgroup: compared with the control, mice of each HFD group had a decreased antioxidantcapacity and a increased inflammatory state,which showed as: MDA LDL-C, adipocyteinflammatory cytokines, plasma leptin and insulin, content of liver and fat and volume of fatcell of plasma and liver increased significantly(P<0.05); CAT and T-AOC of plasma,GSH-Px and T-AOC of liver, and the ADP level of adipose tissue decreasedsignificantly(P<0.05).3) Comparation of redox status and inflammatory status within theHFD groups: compared with DIO group, the antioxidant capacity enhanced and theinflammatory state reduced, which showed as: the ADP level increased significantly(P<0.05),MDA, blood glucose, TG of plasma, plasma leptin and insulin, IL-6, content of liver and fat,volume of adipose tissue decreased significantly(P<0.05). The antioxidant capacity of micefed with long-term high-fat diet showed as: Med>DIO-R>DIO, but the degree ofinflammation was opposite: Med<DIO-R<DIO.4)The ameliorative effects of different dosesof resveratrol on the mice body weight, blood lipids, redox state, and the inflammatory state: (1) Weight and abdominal fat percentage: the treatment of0.6g/kg RSV decreased the weightand abdominal fat percentage significantly and it’s weight loss was not caused by reducingfood intake. The treatment of0.3g/kg RSV could decrease the weight of mice in Med groupand the effect of reducing abdominal fat percentage was significant. RSV treatments had noeffect on body weight of mice of the DIO-R group, but0.6g/kg RSV treatment significantlyreduced their abdominal fat percentage.(2) Redox state: RSV treatments significantlyincreased the antioxidant capacity of mice in DIO group, Med group and DIO-R group, whichwere showed as: CAT and GSH-Px activity of mouse plasma,liver and adipose tissueincreased significantly; ROS and MDA content of liver, adipose tissue decreasedsignificantly(P<0.05). Blood glucose and liquids:0.6g/kg RSV treatment reduced the levels ofblood glucose, the contents of TG of plasma,TC, LDL-C, and HDL-Csignificantly(P<0.05).(4) Inflammatory state: RSV treatment significantly reduced theinflammatory state of the mice in the DIO, Med DIO-R groups, showed as: the adipocyteprotection cytokines ADP level increased significantly, and the adipocyte inflammatorycytokines, resistin, IL-6and TNF-α level, plasma leptin and insulin levels decreasedsignificantly(P<0.05).(5) slices of liver and adipose tissue: RSV treatments significantlyreduced the liver fat content of the high-fat diet mouse, so that some of the fat cell volumewas significantly reduced, which showed a significant dose-dependent. The results showedthat the requirements of different body weight levels of mice on resveratrol were different.0.6g/kg RSV treatment played a significant role in the improvement in the redox state, bloodglucose and lipid, inflammatory state of the DIO mice. Similar results were showed in0.3g/kgresveratrol treatment of DIO-R and Med mice.0.6g/kg RSV treatment caused oxidative stress,dyslipidemia and aggravated inflammation of the DIO-R mice, prompting the dose wasovertop and promoted oxidation.5)Expression and analysis of liver genes:(1) Analysis ofsignificant gene networks and cluster: changes depented channels of weight and RSVtreatment: circadian rhythm, PPAR signaling pathway; the main regulatory pathway ofresveratrol: cell adhesion molecules,leukocyte transendothelial migration and ubiauitinmediated proteolysis, which closely related to inflammatory state and oxidative stress.(2)Expression of gene related to the glucose and lipid metabolism: the gene Cyp7a1whichmaintain the balance of the cholesterol and other lipid in the liver inceased significantly in theDIO-R HFD group, but decreased in the DIO HFD group, prompting metabolic disorders inthe DIO group, and0.6g/kg RSV treatment significantly increased Cyp7a1expression in theliver of DIO mice to maintain the balance of lipid metabolism. SCD1relating withunsaturated fat synthesis was significantly upregulated in DIO-R the HFD group, promptingthe reducing accumulation of saturated fatty acids and triglycerides by increasing theaccumulation of unsaturated fats in the DIO-R group. The Pck1decreased significantly in theDIO-R HFD group and the Med HFD group,which remain stable levels of blood glucose. TheAcacb which reduced the synthesis of fat, decreased in the Med HFD group, and the treatmentof0.6g/kg RSV significantly reduced Acacb expression in the liver of DIO mice but inhibitedfat synthesis. The Socs3increased significantly in the DIO HFD group, prompting leptinresistance in the DIO group. The Irs1decreased significantly in the DIO HFD group,showeding insulin resistance in the DIO group. The Raf1relating with anti-apoptosis decreased in all the HFD groups with adipocyte differentiation intensified, and the treatmentof0.3g/kg RSV can significantly increased the expression of the gene and could inhibiteadipocyte differentiation. RSV treatments enabled the expression levels of genes restored orpartially restored to normal levels in the DIO group. In addition to Pck1, Acacb and Socs3,the trends of gene expression of Cyp7a1and Irs1were similar in the liver.Conclusion:1) Whether HFD induced obesity or not, the high-fat diet could cause miceoxidative stress and chronic systemic inflammatory state, prompting high-fat diet habits ofthose who need exogenous antioxidant supplements.2) The resveratrol can significantlyimproved long-term high-fat diet mice body redox status and chronic inflammatory state,increased the expression of Cyp7a1,Irs1and Raf1and decreased the expression ofAcacb,Socs3.etc.3) The treatment of0.6g/kg resveratrol had a significant improvement inredox state, lipid metabolism, fat cells, cytokine secretion, liver-related gene expression of theDIO mice, and similar results were showed in0.3g/kg resveratrol treatment in DIO-R and Medmice. |
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