摘要
目的:探究母代运动对子代小鼠长期高脂饮食导致骨骼肌功能障碍的保护效应及其机制。方法:雌性C57BL/6小鼠随机分为对照组(maternal control,M-Con)和运动组(maternal exercise,M-Ex)。M-Ex组小鼠孕前4周及孕期进行跑台运动;M-Con组在孕前及孕期均维持常规生活方式,在M-EX组小鼠训练时置于相同环境。M-Con组和M-Ex组与同龄野生型C57BL/6雄性小鼠交配后获得子代小鼠,子代小鼠正常饲养至3周龄后进行为期12周的高脂饮食(high-fat diet,HFD)干预。通过运动表现检测子代小鼠骨骼肌功能;利用组织化学染色分析子代小鼠骨骼肌纤维横截面积、脂质沉积、纤维化和纤维类型;利用蛋白质印迹(Western blot)检测子代小鼠骨骼肌mTOR、P70s6k、Fbx32、TNF-α、TNFR1、AMPK和PGC-1α的蛋白质表达水平;利用实时荧光定量PCR(RT-PCR)检测脂质合成相关基因和线粒体生物发生相关基因表达水平。结果:与正常饲养的野生型小鼠(Sham)相比,M-Con组子代小鼠(HFD.Con)长期高脂饮食后,运动表现显著下降,骨骼肌肌指数和纤维横截面积显著降低,骨骼肌脂质合成相关基因表达显著升高,骨骼肌异位脂质沉积与纤维化面积显著增加,血浆TNF-α水平显著升高,骨骼肌TNF-α及TNFR1蛋白表达显著上调,骨骼肌线粒体功能障碍,琥珀酸脱氢酶染色阳性纤维数量显著降低,AMPK、PGC-1α蛋白表达显著降低。与HFD.Con组相比,M-Ex组子代小鼠(HFD.Ex)骨骼肌AMPK、PGC-1α蛋白表达水平显著升高,线粒体生物发生相关基因表达及琥珀酸脱氢酶染色阳性纤维数量显著增加,脂质合成相关基因及TNF-α和TNFR1蛋白表达水平显著下调,脂质沉积和纤维化面积显著降低,有效抵抗长期高脂饮食导致的骨骼肌功能障碍。结论:母代运动通过激活子代小鼠骨骼肌AMPK-PGC-1α信号通路,促进骨骼肌线粒体生物发生,降低子代小鼠长期高脂饮食导致的肥胖和骨骼肌脂质异位沉积,�
Objective:To investigate the protective effects and underlying mechanisms of maternal exercise on skeletal muscle dysfunction induced by long-term high-fat diet(HFD)in offspring mice.Methods:Female C57BL/6 mice were randomly divided into maternal con group(M-Con)and maternal exercise group(M-Ex).The M-Ex group underwent treadmill exercise for 4 weeks before and during pregnancy,while the M-Con group maintained a regular lifestyle.Both groups were kept in the same environment during the training period.Offspring mice were obtained by mating M-Con and the M-Ex females with age-matched wild-type C57BL/6 males.After normal rearing until 3 weeks of age,the offspring were subjected to a 12-week HFD intervention.Skeletal muscle function in offspring was assessed by exercise performance tests,and the cross-sectional area(CSA),lipid deposition,fibrosis and fiber type of skeletal muscle fibers were analyzed by histochemical staining.The protein expression of mTOR,P70s6k,Fbx32,TNF-α,TNFR1,AMPK and PGC-1αin skeletal muscle was detected by Western blot,and the expression of genes related to lipid synthesis and mitochondrial biogenesis was detected by RT-PCR.Results:Compared to wild-type mice with normal diet(Sham),offspring from the M-Con group(HFD.Con)showed significantly reduced exercise performance,decreased skeletal muscle index and fiber CSA,increased expression of lipid synthesis-related genes,elevated ectopic lipid deposition and fibrosis in skeletal muscle,and higher plasma TNF-αlevel after long-term HFD.Moreover,skeletal muscle TNF-αand TNFR1 protein levels were upregulated,the mitochondrial function was impaired,the number of SDH-stained positive fibers was reduced,and AMPK and PGC-1αprotein expression level were significantly downregulated.Compared with the HFD.Con group,offspring mice(HFD.Ex)from the M-Ex group showed significantly increased expression of AMPK and PGC-1αproteins in skeletal muscle,along with higher levels of mitochondrial biogenesis-related genes and SDH-staining positive fibers.Additionally
作者
石海旺
李婕
于浩洋
张福龙
杨罗丹
段锐
SHI Haiwang;LI Jie;YU Haoyang;ZHANG Fulong;YANG Luodan;DUAN Rui(School of Physical Education and Sports Science,South China Normal University,Guangzhou 510006,China)
出处
《体育科学》
CSSCI
北大核心
2024年第2期50-62,共13页
China Sport Science
基金
国家自然科学基金面上项目(31971096)。
