|Title||Remodeling of skeletal muscle mitochondrial proteome with high-fat diet involves greater changes to β-oxidation than electron transfer proteins in mice.|
|Publication Type||Journal Article|
|Year of Publication||2018|
|Authors||Dasari, S, Newsom, SA, Ehrlicher, SE, Stierwalt, HD, Robinson, MM|
|Journal||Am J Physiol Endocrinol Metab|
Excess fat intake can increase lipid oxidation and expression of mitochondrial proteins, indicating remodeling of the mitochondrial proteome. Yet intermediates of lipid oxidation also accumulate and indicate a relative insufficiency to completely oxidize lipids. We investigated remodeling of the mitochondrial proteome to determine mechanisms of changes to lipid oxidation following high-fat feeding. C57BL/6J mice consumed either a high-fat diet (HFD, 60% fat from lard) or low fat diet (LFD, 10% fat) for 12 weeks. Mice were fasted 4 hours then anaesthetized by sodium pentobarbital for tissue collection. A mitochondrial-enriched fraction was prepared from gastrocnemius muscles and underwent proteomic analysis by high-resolution mass spectrometry. Mitochondrial respiratory efficiency was measured as ATP production per oxygen consumption (P:O). Intramuscular acyl-carnitines were measured by liquid-chromatography mass spectrometry. A total of 658 mitochondrial proteins were identified with 40 having higher and 14 having lower abundance in mice consuming a HFD compared to LFD. Individual proteins that changed with HFD were primarily related to β-oxidation with fewer changes to the electron transfer system. Gene set enrichment analysis identified HFD increased pathways of lipid metabolism and β-oxidation. Intramuscular concentrations of select acyl-carnitines (C18:0) were greater with HFD and reflected dietary lipid composition. Mitochondrial respiratory P:O for lipids was not different between LFD and HFD. Following the 60% fat diet, remodeling of the mitochondrial proteome revealed up-regulation of proteins regulating lipid oxidation that was not evident for all mitochondrial pathways. The accumulation of lipid metabolites with obesity may occur without intrinsic dysfunction to mitochondrial lipid oxidation.
|Alternate Journal||Am. J. Physiol. Endocrinol. Metab.|