Maternal Exercise Protects Offspring Sarcopenic Obesity By Regulating Muscular Fibrosis

Sarcopenic obesity recognized as obese patients with age-related loss of muscle mass and function is at critical risk for geriatric health. We previously demonstrated that maternal obesity not only induces offspring vulnerable to obesity, but also deteriorates offspring muscle development and function. On the other hand, maternal exercise cross-generationally enhances offspring muscular development and fitness; however, the effect of maternal exercise on longitudinal muscle loss and metabolism in sarcopenic obese offspring remains unclear. PURPOSE: To determine the mechanisms underlying longitudinal effect of maternal exercise on sarcopenic obesity. METHODS: Heterozygote mitochondrial polymerase γ (Polgmut/+) mutated mice, known as an aging mouse model, were fed either a control diet or high-fat diet (HFD) to induce sarcopenic obese offspring mice (wild-type, WT, or Polgmut/mut). In another set, exercise during pregnancy was subjected to Polg mutated mice. Six-month-old offspring mice were utilized for cardiovascular and maximal strength fitness tests. Then, 9-month-old offspring mice were used for sample collection for biochemical and histochemical analyses, including RNA-seq, gene expression, immunoblotting, and immunohistochemistry (IHC). Statistical analyses were conducted using two-way ANOVA followed by Tukey’s test and unpaired Student’s t-test. RESULTS: Maternal high-caloric diet during pregnancy induced offspring sarcopenic obesity by loss of muscle mass and reduced expression of development markers determined by RNA-seq and excessive adiposity in Polg mutated fetal and aged offspring muscle (P < 0.05). Maximal oxygen consumption rates (OCRs) and grip strength of Polg mutation-induced aged offspring were decreased in response to maternal HFD challenge (P < 0.05), which might be due to the increased muscular fibrosis (P < 0.05). On the other hand, maternal exercise dynamically expressed muscle developmental markers (P < 0.05) and protected adverse outcomes in mitochondrial biogenesis and energy metabolism (P < 0.05) due to maternal HFD challenge. CONCLUSION: Maternal exercise during pregnancy protected offspring muscular fibrosis induced by maternal HFD challenge and Polg mutation, thereby leading to healthy metabolism and normal muscular function. This work was supported by the National Institutes of Health Grant R01-HD067449 and R21-AG084142.