Exercise Intergenerationally Drives Muscle-Based Thermogenesis and Myogenesis in Offspring Impaired Due to Maternal Obesity

Abstract

Abstract Objectives Maternal obesity (MO) predisposes metabolic dysfunction in offspring muscle. Skeletal muscle-dependent non-shivering thermogenesis (NST) is emerging as a critical mechanism for maintaining energy homeostasis, but the effects of maternal exercise on muscle-based thermogenesis in offspring remains unexplored. In addition, the impact of maternal obesity and exercise on fetal muscle development is unclear, which will also be examined. The objective of the current study is to explore the effects of maternal exercise on muscle-based thermogenesis and myogenesis in fetuses impaired due to MO. Methods Female C57BL/6 J mice were randomized and assigned to either control (CON, 10 kcal% from fat) or obesogenic diet (OB, 60 kcal% from fat) for 8 weeks to induce obesity and then mated. Then, pregnant mice in obesogenic diet were further separated into two groups with/without exercise (daily 60 min exercise) during pregnancy, which resulted in three treatments: control (CON), OB, and OB-EX (n = 6 per group). Fetal skeletal muscles were collected at embryonic day 18.5 (E18.5). In another cohort of animals, maternal mice were allowed to give birth and surface temperature of neonates was measured. Statistical analysis were conducted using one way analysis of variance (ANOVA); a pregnancy/litter was considered as an experimental unit. Results OB reduced surface temperature of neonates (P < 0.01). In E18.5 fetal muscle, OB downregulated muscle-based thermogenic gene expression (P < 0.05), including Sln, Serca2, and Ryr1. In addition, the expression of mitochondriogenic genes (P < 0.05), including Ppargc1a and Tfam, was also reduced in OB fetal female and male muscle. These adverse changes were prevented due to exercise during pregnancy. Furthermore, maternal exercise protected against the downregulation of myogenesis-related gene expression, including MyoD, Myogenin, Myf5, and Pax7, due to MO. Conclusions Exercise during pregnancy enhanced muscle-based thermogenic gene expression and myogenesis which were impaired due to MO, suggesting that maternal exercise intergenerationally improves metabolic health of offspring. Funding Sources Supported by NIH Grant R01HD067449.