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

Cell Metab. 2024 Jun 4;36(6):1411-1429.e10. doi: 10.1016/j.cmet.2023.12.021. Epub 2024 May 2.

Abstract

Mitochondria have diverse functions critical to whole-body metabolic homeostasis. Endurance training alters mitochondrial activity, but systematic characterization of these adaptations is lacking. Here, the Molecular Transducers of Physical Activity Consortium mapped the temporal, multi-omic changes in mitochondrial analytes across 19 tissues in male and female rats trained for 1, 2, 4, or 8 weeks. Training elicited substantial changes in the adrenal gland, brown adipose, colon, heart, and skeletal muscle. The colon showed non-linear response dynamics, whereas mitochondrial pathways were downregulated in brown adipose and adrenal tissues. Protein acetylation increased in the liver, with a shift in lipid metabolism, whereas oxidative proteins increased in striated muscles. Exercise-upregulated networks were downregulated in human diabetes and cirrhosis. Knockdown of the central network protein 17-beta-hydroxysteroid dehydrogenase 10 (HSD17B10) elevated oxygen consumption, indicative of metabolic stress. We provide a multi-omic, multi-tissue, temporal atlas of the mitochondrial response to exercise training and identify candidates linked to mitochondrial dysfunction.

Keywords: HSD17B10; acetylome; aerobic; exercise; metabolism; metabolomics; mitochondria; multi-omics; proteomics; transcriptomics.

MeSH terms

  • Adipose Tissue, Brown / metabolism
  • Adrenal Glands / metabolism
  • Animals
  • Female
  • Humans
  • Male
  • Mitochondria* / metabolism
  • Multiomics
  • Muscle, Skeletal / metabolism
  • Physical Conditioning, Animal*
  • Rats
  • Rats, Sprague-Dawley