Maternal exercise programs skeletal muscle metabolic dysfunction in offspring mice challenged with high fat diet.

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Exercise, including maternal exercise becomes increasingly less common. Though improper maternal nutrition and obesity are known to affect fetal muscle development and predisposes offspring to metabolic dysfunction, the effects of maternal exercise (ME) on fetal muscle development and offspring metabolic health are largely undefined.PURPOSETo investigate the effects of maternal exercise on mitochondrial biogenesis during fetal muscle development, and muscle function and metabolic health in offspring following high fat diet (HFD) challenge.METHODSFemale C57BL/6J mice were randomized and assigned into a control (CON) or an exercise (EX) group (n = 6 per group) fed a normal chow. Exercise was performed every morning for 60 min during pregnancy. Then, the animals were mated, and the skeletal muscle samples were collected at embryonic day 18.5, weaning, and after 8 weeks of high fat diet (HFD; 60 kcal% from fat) challenge in both females and males. Statistical analysis were conducted using student’s t‐test and/or one/two way analysis of variance (ANOVA).RESULTSME muscle fiber diameters and enhanced muscle endurance capacity in offspring (P < 0.05), which were positively associated with switching muscle fibers from type IIb/x to type I and IIa and mitochondrial biogenesis (P < 0.05), but negatively correlated with atrophy‐related Atrogin‐1 and Murf1 gene expression (P < 0.05). Mechanistically, ME enhanced DNA demethylation of Pgc‐1a promoter and its expression during fetal muscle development. Importantly, such changes in DNA methylation maintained in offspring muscle before and after HFD challenge, resulting in elevated Pgc‐1a mRNA expression and increased contents of PGC‐1a1 and 4 isoforms, which improved metabolic health.CONCLUSIONSThis study identifies that ME enhances DNA demethylation of the Pgc‐1a promoter during fetal muscle development, which has programming effects on the exercise endurance capacity and metabolic health of muscle in offspring.Support or Funding InformationThis work was supported by National Institutes of Health Grants R01‐HD067449.Maternal exercise (ME) enhances adaptation to endurance training of offspring mice (A,B) and the proportion of muscle type I fiber composition before and following HFD challenge (C). ME decreases muscle atrophy‐related genes following HFD challenge (D,E). Data are mean ± s.e.m. and each dot represents one litter.; two‐sided P values by unpaired Student’s t‐test (D,E) or two‐way repeated measures ANOVA followed by Tukey’s test (B).Figure 1