PGC-1α-mediated changes in phospholipid profiles of exercise-trained skeletal muscle

Abstract

This article is available online at http://www.jlr.org infl uences cell permeability and receptor stability at the cell membrane, these phospholipids may contribute to exercise training-mediated functional changes in the skeletal muscle. Phospholipids are important structural components of membranes, and they infl uence a number of physical properties related to membrane function, including fl uidity, permeability, and the anchoring of membrane-related proteins. Because altering dietary fatty acids ( 1-3 ) and Abstract Exercise training infl uences phospholipid fatty acid composition in skeletal muscle and these changes are associated with physiological phenotypes; however, the molecular mechanism of this infl uence on compositional changes is poorly understood. Peroxisome proliferator-activated receptor ␥ coactivator 1 ␣ (PGC-1 ␣ ), a nuclear receptor coactivator, promotes mitochondrial biogenesis, the fi ber-type switch to oxidative fi bers, and angiogenesis in skeletal muscle. Because exercise training induces these adaptations, together with increased PGC-1 ␣ , PGC-1 ␣ may contribute to the exercise-mediated change in phospholipid fatty acid composition. To determine the role of PGC-1 ␣ , we performed lipidomic analyses of skeletal muscle from genetically modified mice that overexpress PGC-1 ␣ in skeletal muscle or that carry KO alleles of PGC-1 ␣ . We found that PGC-1 ␣ affected lipid profi les in skeletal muscle and increased several phospholipid species in glycolytic muscle, namely phosphatidylcholine (PC) (18:0/22:6) and phosphatidylethanolamine (PE) (18:0/22:6). We also found that exercise training increased PC (18:0/22:6) and PE (18:0/22:6) in glycolytic muscle and that PGC-1 ␣ was required for these alterations. Because phospholipid fatty acid composition

Looking Beyond Structure: Membrane Phospholipids of Skeletal Muscle Mitochondria

“…It is not clear how exercise training increases synthesis/import of other mitochondrial phospholipids, but such a mechanism(s) likely involves an action of peroxisome proliferator-activated receptor gamma coactivator 1α (PGC1α). Skeletal muscle-specific overexpression of PGC1α is sufficient to increase PC and PE, while its absence results in ablation of exercise-induced increases in cellular PC and PE [63, 69]. PGC1α may also play a role in CL synthesis [68], though Akt and AMP-activated protein kinase (AMPK) are also likely involved [47, 70].…”

Metabolism and functions of docosahexaenoic acid‐containing membrane glycerophospholipids

“…In several studies in mice, rats, and humans, DHAcontaining GPLs were increased by endurance exercise training independently of diet, and DHA-containing GPL levels showed positive correlations with oxidative capacity of the skeletal muscle [110][111][112][113][114]. In mice, exercise-induced increases of DHA in PE were observed in extensor digitorum longus muscles, whereas more oxidative soleus muscle already had high DHA in PE even without training [110].…”

PLS‐ROG: Partial least squares with rank order of groups

“…Using this feature, metabolites can be selected using statistical hypothesis testing of factor loading in PCA. This approach is easy for biologist to use and has been applied for metabolomic data analysis in practice …”

“…This approach is easy for biologist to use and has been applied for metabolomic data analysis in practice. 7,8,12,13 Partial least squares regression and PLS-DA compute scores that are orthogonal with each other via a deflation procedure. However, in PLS-R and PLS-DA, this procedure does not allow scores to be represented by linear combination of each metabolite level.…”