@article{3129d54b2dc64a6aae137203a0496686,
title = "Remodeling of skeletal muscle mitochondrial proteome with high-fat diet involves greater changes to β-oxidation than electron transfer proteins in mice",
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, indicating a relative insufficiency to completely oxidize lipids. We investigated remodeling of the mitochondrial proteome to determine mechanisms of changes in lipid oxidation following high-fat feeding. C57BL/6J mice consumed a high-fat diet (HFD, 60% fat from lard) or a low-fat diet (LFD, 10% fat) for 12 wk. Mice were fasted for 4 h and then anesthetized by pentobarbital sodium overdose 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 the ratio of ATP production to O2 consumption. Intramuscular acylcarnitines were measured by liquid chromatography-mass spectrometry. A total of 658 mitochondrial proteins were identified: 40 had higher abundance and 14 had lower abundance in mice consuming the HFD than in mice consuming the LFD. Individual proteins that changed with the HFD were primarily related to β-oxidation; there were fewer changes to the electron transfer system. Gene set enrichment analysis indicated that the HFD increased pathways of lipid metabolism and β-oxidation. Intramuscular concentrations of select acylcarnitines (C18:0) were greater in the HFD mice and reflected dietary lipid composition. Mitochondrial respiratory ATP production-to-O2 consumption ratio for lipids was not different between LFD and HFD mice. After the 60% fat diet, remodeling of the mitochondrial proteome revealed upregulation 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.",
keywords = "Lipid, Mitochondria, Obesity, Proteomics, Skeletal muscle",
author = "Surendra Dasari and Newsom, {Sean A.} and Ehrlicher, {Sarah E.} and Stierwalt, {Harrison D.} and Robinson, {Matthew M.}",
note = "Funding Information: This study was funded by National Institute of Diabetes and Digestive and Kidney Diseases Grant K01 DK-103829 (M. M. Robinson). This project was supported in part through the Mayo Clinic Medical Genome Facility Proteomics Core and its supporting grant from the National Cancer Institute (5P30 CA-15083-43C1). Research reported in this publication was supported in part by National Institutes of Health Grant KL2 TR-002370 (S. A. Newsom) awarded through the Oregon Clinical and Translational Research Institute by National Center for Advancing Translational Sciences under Grant UL1 TR-0002369. Funding Information: We thank Dr. Sreekumaran Nair, Dr. Ian Lanza, Dr. Manjunatha Shan-karappa, Kate Klaus, and Dawn Morse (Mayo Clinic) and Emily Burney and Bergen Sather (Oregon State University) for skilled assistance and contributions; Carrie Jo Heppelmann, Michael Holmes, and Dr. Bob Bergen 3rd (Proteomics Core at Mayo Clinic); Dr. Bryan Bergman and Dr. Kathleen Harrison (University of Colorado Denver) for assistance with lipidomics analysis; Felix Morales-Palomo (University of Castilla-La Mancha) for technical support; and Dr. Donald Jump (Oregon State University) for generously providing primers for quantitative PCR analysis. This study was funded by National Institute of Diabetes and Digestive and Kidney Diseases Grant K01 DK-103829 (M. M. Robinson). This project was supported in part through the Mayo Clinic Medical Genome Facility Proteomics Core and its supporting grant from the National Cancer Institute (5P30 CA-15083-43C1). Research reported in this publication was supported in part by National Institutes of Health Grant KL2 TR-002370 (S. A. Newsom) awarded through the Oregon Clinical and Translational Research Institute by National Center for Advancing Translational Sciences under Grant UL1 TR-0002369. Publisher Copyright: {\textcopyright} 2018 American Physiological Society. All rights reserved.",
year = "2018",
month = oct,
doi = "10.1152/ajpendo.00051.2018",
language = "English (US)",
volume = "315",
pages = "E425--E434",
journal = "American Journal of Physiology",
issn = "0193-1849",
publisher = "American Physiological Society",
number = "4",
}