Mechanistic Study of Maternal Exercise Mitigatinging High-Fat Diet Induced Skeletal Muscle Dysfunction in Offspring Mice
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-1α in 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-α level after long-term HFD.Moreover,skeletal muscle TNF-α and TNFR1 protein levels were upregulated,the mitochondrial function was impaired,the number of SDH-stained positive fibers was reduced,and AMPK and PGC-1α protein 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-1α proteins in skeletal muscle,along with higher levels of mitochondrial biogenesis-related genes and SDH-staining positive fibers.Additionally,the expression of lipid synthesis-related genes and TNF-α and TNFR1 proteins was significantly downregulated,reducing lipid deposition and fibrosis,thereby resisting skeletal muscle dysfunction caused by a long-term high-fat diet.Conclusions:Maternal exercise actives AMPK/PGC-1α signaling pathway in offspring skeletal muscle,promoting mitochondrial biogenesis,reducing obesity and ectopic lipid deposition induced by long-term HFD,and inhibiting serum TNF-α levels and skeletal muscle TNFR1 protein expression.These effects effectively alleviate muscle atrophy and fibrosis in offspring,protecting skeletal muscle against metabolic dysfunction.
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