Journal
PROTEOMICS
Volume 18, Issue 5-6, Pages -Publisher
WILEY
DOI: 10.1002/pmic.201700375
Keywords
fatty acid oxidation; insulin resistance; metabolism; mitochondria; obesity
Funding
- Max-Planck-Society for the Advancement of Science
- Federation of European Biochemical Societies (FEBS)
- Swedish Diabetes Foundation [DIA2015-052]
- Novo Nordisk Foundation Center for Protein Research [NNF14CC001]
- Swedish Research Council [2011-3550]
- Novo Nordisk Foundation Center for Basic Metabolic Research Copenhagen, Denmark
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Skeletal muscle insulin resistance, an early metabolic defect in the pathogenesis of type 2 diabetes (T2D), may be a cause or consequence of altered protein expression profiles. Proteomics technology offers enormous promise to investigate molecular mechanisms underlying pathologies, however, the analysis of skeletal muscle is challenging. Using state-of-the-art multienzyme digestion and filter-aided sample preparation (MED-FASP) and a mass spectrometry (MS)-based workflow, we performed a global proteomics analysis of skeletal muscle from leptin-deficient, obese, insulin resistant (ob/ob) and lean mice in mere two fractions in a short time (8 h per sample). We identified more than 6000 proteins with 118 proteins differentially regulated in obesity. This included protein kinases, phosphatases, and secreted and fiber type associated proteins. Enzymes involved in lipid metabolism in skeletal muscle from ob/ob mice were increased, providing evidence against reduced fatty acid oxidation in lipid-induced insulin resistance. Mitochondrial and peroxisomal proteins, as well as components of pyruvate and lactate metabolism, were increased. Finally, the skeletal muscle proteome from ob/ob mice displayed a shift toward the slow fiber type. This detailed characterization of an obese rodent model of T2D demonstrates an efficient workflow for skeletal muscle proteomics, which may easily be adapted to other complex tissues.
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