The effects of exercise training on the skeletal muscle (SKM) lipidome and mitochondrial function have not been thoroughly explored in individuals with
Type 2 diabetes (T2D). We hypothesize that 10 wk of supervised
endurance training improves SKM mitochondrial function and
insulin sensitivity that are related to alterations in
lipid signatures within SKM of T2D (males n = 8). We employed integrated multi-omics data analyses including ex vivo lipidomics (MS/MS-shotgun) and transcriptomics (
RNA-Seq). From biopsies of SKM, tissue and primary myotubes mitochondrial respiration were quantified by high-resolution respirometry. We also performed hyperinsulinemic-euglycemic clamps and blood draws before and after the training. The lipidomics analysis revealed that
endurance training (>95% compliance) increased
monolysocardiolipin by 68.2% (P ≤ 0.03), a putative marker of mitochondrial remodeling, and reduced total
sphingomyelin by 44.8% (P ≤ 0.05) and
phosphatidylserine by 39.7% (P ≤ 0.04) and tended to reduce
ceramide lipid content by 19.8%.
Endurance training also improved intrinsic mitochondrial respiration in SKM of T2D without alterations in
mitochondrial DNA copy number or
cardiolipin content.
RNA-Seq revealed 71 transcripts in SKM of T2D that were differentially regulated.
Insulin sensitivity was unaffected, and HbA1c levels moderately increased by 7.3% despite an improvement in cardiorespiratory fitness (V̇o2peak) following the training intervention. In summary,
endurance training improves intrinsic and cell-autonomous SKM mitochondrial function and modifies
lipid composition in men with T2D independently of alterations in
insulin sensitivity and
glycemic control.