| Feeding on high- fat diet(HFD) will lead to two phenotypes- obesity prone(OP) and obesity resistant(OR). Studies had shown that HFD induced oxidative stress is one of the important factors affecting the pathogenesis of osteoporosis, and quercetin plays an important role in regulating oxidative stress, thyroid hormone metabolism and bone metabolism. The thesis aims to explore the femur property and energy metabolism changes in HFD induced OP and OR mice and to understand the intervention effect of quercetin and its possible mechanism. Provided theoretical base of prevention and treatment of quercetin on osteoporosis induced by HFD.To investigate the effect of HFD on bone of OP and OR mice, we induced a mice model of different obesity phenotypes. Part 1: mice were randomly divided into 1) regular diet group(C), 2) HFD group, 3) groups of HFD+different doses of quercetin: 0.25%(Q1), 0.05%(Q2), 0.1%(Q3). After feeding for 7 weeks, The lightest 1/3 HFD mice were obesity OR group, and the heaviest 1/3 were OP group. Each group was executed at the end of 7t h and 17 th week. Blood parameters, femur parameters, redox state, expressions of osteoblast and osteoclast differentiation related gene expressions, and anti-oxidant related gene expressions were measured respectively. Part 2: comparison of the effects of restoring diet and adding quercetin. Mice were randomly divided into: regular diet group(C) high fat diet gro up(HFD). OP and OR were induced in the same way as part 1. After feeding HFD for 10 weeks, the OP and OR mice were both divided into 3 groups: continu ing fed HFD(OP-HFD, O R-HFD), changing HFD into a regular diet(OP-C, OR-C), HFD+0.1% quercetin(OP+Q, OR+Q). Put the mice to death at the end of the 17 t h week. Indicators were measured the same as part 1.After fed on HFD for 7 weeks, The bone mineral density, maximum load, diameter of femur, ash weight, dry weight, and femoral bone calcium content of OR mice were significantly lower than group C(P<0.05). The diameter of femur, ash weight, dry weight, length of OP mice was significantly higher than group C and OR(P<0.05). Plasma T3 levels and the expression of TRα1 were both significantly increased in OP and OR mice, but OP mice was higher than OR mice. The expression of GSK-3β was down regulated, and the expression of Nrf2 was up regulated in OR mice, while the OP mice had the opposite results. SOD level in OR mice was significantly lower(P<0.05), while MDA was significantly higher(P<0.05). SOD level in OP mice was significantly lower(P<0.05) than group C and group OR, while the MDA was significantly higher(P<0.05) than that of both group C and group OR. The expressions of osteoblast differentiation marker genes Bglap2, Runx2, col1a1 were significantly upregulated while the expressions of osteoclast differentiation marker genes RANGK L/OPG, CTSK were significant down regulated(P<0.05) in both OP and O R mice. These results suggested that 7 weeks of HFD induced oxidative stress in femur of OP and O R mice, but OP mice was worse. Higher T3 level and bone turnover lead to increased femur property in OP mice.After fed on HFD for 17 weeks, GSH/GSSG, T-AOC, SOD levels were significantly reduced, and MDA levels were significantly increased in both OP and OR mice. The expressions of osteoblast differentiation marker genes were significantly upregulated while the expressions of osteoclast differentiation marker genes were significant down regulated(P<0.05) in both OP and OR mice. Femur property parameters were decreased in both OP and OR mice. These results suggested that femur antioxidant capacity were weakened, femur had severe oxidative stress in both Group OP and OR. Q uercetin could improve the antioxidant capacity of the femur by inhibiting the expression of GSK-3β, and activating Nrf2. Which lead to increased osteoblast differentiation and inhibited osteoclast differentiation of OP mice, thus femur property was increased. After 7 weeks of HFD, 0.05% quercetin were able to improve the redox state of HFD mice. After 17 weeks of HFD, 0.1% of quercetin could improved the femur property of HFD-fed mice.Reverting to a regular diet for 7 weeks could better recover the redox state and femur property of OR mice than adding quercetin. Femur oxidative stress was more severe in OP mice than in OR mice, thus reverting to a regular diet improved femur property of OP mice slightly. Quercetin could improve the redox state in femur of OP mice thus improved femur property.In conclusion, feeding on a short-term HFD decreased femoral antioxidant capacity of OP and OR mice, bone turnover rate was faster in OP mice than in OR mice. OP mice had increased femur property; Feeding on a long-term HFD, OP and O R mice both had severe femoral oxidative stress which reduced femur property. Adding appropriate amount of quercetin improved femoral antioxidant capacity which lead to inhibited bone absorption and increased bone formation. So that femur property was increased. Reverting to a regular diet could improve femur property of O R mice effectively. Adding quercetin in HFD could better improve femur property of OP mice... |
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