Pino 2019 Physiol Genomics
|Pino MF, Stephens NA, Eroshkin AM, Yi F, Hodges A, Cornnell HH, Pratley RE, Smith SR, Wang M, Han X, Coen PM, Goodpaster BH, Sparks LM (2019) Endurance training remodels skeletal muscle phospholipid composition and increases intrinsic mitochondrial respiration in men with type 2 diabetes. Physiol Genomics [Epub ahead of print].|
Abstract: 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 weeks 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 [RNAseq]. 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 % (MLCL, p ≤ 0.03), a putative marker of mitochondrial remodeling and reduced total sphingomyelin by 44.8 % (SM, p ≤ 0.05) and phosphatidylserine by 39.7 % (PS, ≤ 0.04), and tended to reduce ceramides 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. RNAseq 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 (VO2peak) following the training intervention. In summary, endurance training improves intrinsic and cell-autonomous SKM mitochondrial function and modifies lipid composition in men with T2D independent of alterations in insulin sensitivity and glycemic control.
Labels: MiParea: Respiration, Exercise physiology;nutrition;life style Pathology: Diabetes
Organism: Human Tissue;cell: Skeletal muscle Preparation: Permeabilized cells, Permeabilized tissue
Coupling state: LEAK, OXPHOS, ET Pathway: N, NS HRR: Oxygraph-2k