Abstract
Background: Sarcopenia, recognized as an age-related loss of muscle mass and function, is a critical risk for geriatric health. We previously demonstrated that maternal high-fat diet (HFD) suppresses mitochondrial biogenesis during fetal skeletal muscle development, but the longitudinal effect of maternal HFD challenge on offspring muscle sarcopenia and fitness impairment remains unclear. Mitochondrial polymerase γ (PolG) mutation accelerates mitochondrial DNA mutations and leads to premature aging. Methods: To determine the mechanisms underlying the longitudinal effect of maternal HFD challenge on offspring sarcopenia and aging, heterozygote mitochondrial polymerase γ mutated (PolgAmut/+) female mice were fed either a control diet (CD) or HFD during pregnancy, which were mated with heterozygote PolgA male mice. Thus, we had four experimental groups: maternal CD (M-CD) + WT, M-CD + PolgAmut, M-HFD + WT and M-HFD + PolgAmut. Six-month-old offspring mice were utilized for testing metabolic health, maximal muscle strength and cardiorespiratory fitness capacity. Then, 9-month-old offspring mice were used for biochemical and histochemical analyses. Results: Maternal high-calorie diet during pregnancy decreased offspring muscle strength and cardiorespiratory function (p < 0.05), which were associated with loss of muscle mass (p < 0.05). These adverse outcomes were most dramatic in M-HFD with PolG mutation (p < 0.05). Maternal HFD challenge activated muscle atrophy signalling, including MuRF1 and Atrogin-1 (p < 0.05), which were worsened in PolgA mice (p < 0.05). Furthermore, M-HFD increased the accumulation of intramuscular fibrosis in PolgA offspring (p < 0.05). In addition, M-HFD increased the risk of neuromuscular damage by attenuating GABAA receptor pathway in PolgA mice (p < 0.05). Conclusions: Maternal high-calorie diet during pregnancy induced offspring muscle atrophy and intramuscular fibrosis, especially with PolG mutation, underscoring mitochondrial dysfunction in linking maternal HFD to offspring premature aging.