Transcriptomic and epigenetic responses to short-term nutrient-exercise stress in humans.

Area of Science:

• Exercise physiology
• Molecular biology
• Nutritional science

Background:

• High-fat diets (HFD) impair skeletal muscle metabolic flexibility and induce insulin resistance.
• Exercise training improves insulin sensitivity and substrate handling in skeletal muscle.

Purpose of the Study:

• To investigate the genomic mechanisms by which exercise training ameliorates the deleterious effects of a high-fat diet on human skeletal muscle.
• To examine the transcriptional and epigenetic responses to HFD and resistance exercise.

Main Methods:

• Genome-wide gene expression profiling.
• Genome-wide DNA methylation profiling.
• Analysis of human skeletal muscle samples from 9-day high-fat diet (HFD) and HFD with resistance exercise (Ex-HFD) interventions.

Main Results:

• HFD induced immune and inflammatory gene expression, which was not affected by exercise.
• Exercise significantly altered the expression of genes related to muscle growth and structure.
• Significant DNA methylation changes were observed in both HFD and Ex-HFD groups.
• PYGM showed epigenetic regulation in both groups, while ANGPTL4 was regulated only after exercise.

Conclusions:

• Short-term exercise did not prevent HFD-induced inflammation but initiated genomic adaptations potentially protecting skeletal muscle from atrophy.
• Epigenetic modifications provide mechanistic insights into gene-specific regulation of inflammatory and metabolic processes in skeletal muscle.