Childhood obesity impairs muscle growth and function via altered myogenic and adipogenic factors

Background: Childhood obesity is a critical public health issue that detrimentally affects muscle growth and function. Although the condition is widely prevalent, the specific mechanisms through which obesity induces these muscular impairments, as well as effective prevention strategies, remain insufficiently explored. Methods: We conducted a cross-sectional analysis of 155 children, categorized into obese and normal-weight groups, to evaluate the relationship between obesity and muscle health parameters. Concurrently, we established a murine model of obesity by exposing 3- and 8-week-old mice to a high-fat diet (HFD) to investigate the underlying mechanisms behind obesity’s effects on muscle mass, structure, and function. Additionally, vitamin C supplementation was explored as a potential preventative strategy against HFD-induced muscle impairments. Results: In juvenile mice, a HFD significantly increased both body and intramuscular fat while decreasing relative muscle mass and strength, mirroring the patterns observed in obese children. The diet downregulated key myogenic regulatory factors (MRFs) and myosin heavy chains (MHCs) in muscle tissue, alongside an upregulation of adipogenic pathways, contributing to impaired muscle growth and function. Notably, these adverse effects persisted into adulthood despite subsequent weight loss, underscoring the long-term impact of early dietary interventions. In contrast, adult mice did not exhibit significant muscular impairments after 4 weeks of HFD, suggesting age-specific dietary responses. Vitamin C supplementation effectively ameliorated these HFD-induced impairments in juvenile mice, enhancing muscle function and modifying gene expression related to muscle growth and fat metabolism. Conclusion: These results demonstrate that childhood obesity impairs muscle growth and function by altering myogenic and adipogenic pathways, effects which vitamin C supplementation can mitigate. Further research is needed to explore how a HFD induces these impairments, potentially through mechanisms such as fat accumulation and inflammation.