The mitochondrial multi-omic response to exercise training across rat tissues.

Area of Science:

• Exercise physiology
• Mitochondrial biology
• Metabolomics

Background:

• Mitochondria are vital for metabolic homeostasis.
• Endurance training impacts mitochondrial function, but adaptations are not fully characterized.
• A systematic, multi-tissue analysis of exercise-induced mitochondrial changes is needed.

Purpose of the Study:

• To comprehensively map the temporal, multi-omic changes in mitochondrial analytes across multiple tissues in response to endurance training.
• To identify specific tissues and molecular pathways affected by exercise.
• To explore the link between exercise-induced mitochondrial adaptations and human metabolic diseases.

Main Methods:

• Multi-omic analysis (proteomics, metabolomics) of mitochondrial analytes.
• Longitudinal study design with 19 tissues from male and female rats trained for 1, 2, 4, or 8 weeks.
• Gene knockdown experiments to investigate the role of specific mitochondrial proteins.

Main Results:

• Significant mitochondrial adaptations were observed in the adrenal gland, brown adipose tissue, colon, heart, and skeletal muscle.
• The colon exhibited non-linear response dynamics, while brown adipose and adrenal tissues showed downregulated mitochondrial pathways.
• Protein acetylation and lipid metabolism shifted in the liver; oxidative proteins increased in striated muscles.
• Exercise-upregulated networks were found to be downregulated in human diabetes and cirrhosis.
• Knockdown of HSD17B10 increased oxygen consumption, suggesting metabolic stress.

Conclusions:

• Exercise training induces widespread and tissue-specific mitochondrial adaptations.
• The study provides a valuable temporal atlas of mitochondrial responses to exercise.
• Identified mitochondrial pathways and proteins may be relevant to metabolic dysfunction in diseases like diabetes and cirrhosis.