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

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE280926 | GEO | 2026/04/22

REPOSITORIES: GEO

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Project description:An 8-week high fat palm oil diet causes obesity and insulin resistance in C57BL/6J mice, but induces only small changes in the muscle transcriptome. Introduction: The metabolic syndrome (MS) is a cluster of metabolic abnormalities linked to an increased risk of type 2 diabetes and cardiovascular diseases. Two major characteristics of the MS are obesity and insulin resistance. In the present study we investigated the effect of obesity and insulin resistance on the mouse muscle transcriptome. Methods: C57BL/6J mice were fed a palm oil-based low fat diet (LFD) or high fat diet (HFD) for eight weeks. Microarray analysis was performed by using two complementary strategies: (1) 8-week HFD transcriptome versus 8-week LFD transcriptome and (2) transcriptome of mice sacrificed at the start of the intervention versus 8-week LFD transcriptome and 8-week HFD transcriptome, respectively. Results: HFD mice develop obesity and whole-body insulin resistance. Despite these metabolic disturbances we found that HFD induces relatively small changes in gene expression (< 1.3 fold). Only the up-regulation of FA oxidation and the down-regulation of the MAPK cascade were specific for the HFD intervention. Eight-weeks of aging induced more changed gene expression levels than the HFD, including genes involved in cell-cell interaction and development. Conclusion: Eight weeks of aging induce more pronounced changes in the muscle transcriptome than an HFD. Since only one strategy revealed the transcriptional down-regulation of the MAPK cascade, whereas both strategies showed the up-regulation of FA oxidation we suggest the use of complementary analysis strategies by the genome-wide search of gene expression changes induced by mild interventions, such as an HFD. Keywords: diet intervention and time course In this study, C57BL/6J mice were fed a high fat (HF) diet for 8 weeks to induce obesity and insulin resistance. Plasma levels of the adipokines leptin and adiponectin were measured. To investigate how these metabolic disturbances will influence the skeletal muscle transcriptome we performed whole-genome microarray analysis. Functional implications were assessed by analyses of predefined gene sets based on Gene Ontology, biochemical, metabolic and signaling pathways.

Project description:Maternal obesity can program metabolic syndrome in offspring but the mechanisms are not well characterized. Moreover, the consequences of maternal overnutrition in the absence of frank obesity remain poorly understood. This study aimed to determine the effects of maternal consumption of a high fat-sucrose diet on the skeletal muscle metabolic and transcriptional profiles of adult offspring. Female Sprague Dawley rats were fed either a diet rich in saturated fat and sucrose (HFD, 23.5% fat, 20% sucrose wt/wt) or a standard chow diet (NFD, 7% fat, 10% sucrose w/w) for the 3 weeks prior to mating and throughout pregnancy and lactation. Although maternal weights were not different between groups at conception or weaning, HFD dams were ~22% heavier than chow fed dams from mid-pregnancy until 4 days post-partum. Adult male offspring of HFD dams were not heavier than controls but demonstrated features of insulin resistance including elevated plasma insulin concentration (+40%, P<0.05). Next Generation mRNA Sequencing was used to identify differentially expressed genes in the soleus muscle of offspring, and Gene Set Enrichment Analysis (GSEA) to detect coordinated changes that are characteristic of a biological function. GSEA identified 15 pathways enriched for up-regulated genes, including cytokine signaling (P<0.005), starch and sucrose metabolism (P<0.017), and inflammatory response (P<0.024). A further 8 pathways were significantly enriched for down-regulated genes including oxidative phosphorylation (P<0.004) and electron transport (P<0.022). Western blots confirmed a ~60% reduction in the phosphorylation of the insulin signaling protein Akt (P<0.05) and ~70% reduction in mitochondrial complexes II (P<0.05) and V expression (P<0.05). On a normal diet, offspring of HFD dams developed an insulin resistant phenotype, with transcriptional evidence of muscle cytokine activation, inflammation and mitochondrial dysfunction. These data indicate that maternal overnutrition, even in the absence of pre-pregnancy obesity can promote metabolic dysregulation and predispose offspring to type 2 diabetes. Messenger RNA profile of skeletal muscle of male offspring from female Sprague Dawley rats fed either a diet rich in saturated fat and sucrose (HFD, 23.5% fat, 20% sucrose wt/wt) or a standard chow diet (NFD, 7% fat, 10% sucrose w/w) for the 3 weeks prior to mating and throughout pregnancy and lactation. There were 5 HFD samples compared to 6 NFD control samples.

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

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