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 |
Date Published | 05/2018 |
ISSN | 1522-1555 |
Abstract | 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. |
DOI | 10.1152/ajpendo.00051.2018 |
Alternate Journal | Am. J. Physiol. Endocrinol. Metab. |
PubMed ID | 29812987 |