Proteomics

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Proteomics analysis of skeletal muscle from leptin-deficient ob/ob mice reveals adaptive remodeling of metabolic characteristics and fiber type composition


ABSTRACT: Skeletal muscle insulin resistance, an early metabolic defect in the pathogenesis of type 2 diabetes, may be a cause or consequence of altered protein expressions profiles. Proteomics technology offers enormous promise to investigate molecular mechanisms underlying pathologies, however, the analysis of skeletal muscle is challenging. Using a state-of-the-art mass spectrometry (MS) based workflow, we performed a global proteomics analysis of skeletal muscle from leptin-deficient, obese, type 2 diabetic (ob/ob) and lean mice, identifying more than 6,000 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 likewise increased. Finally, the skeletal muscle proteome from ob/ob mice displayed a shift towards the ‘slow fiber type’. This detailed characterization of obese rodent models of type 2 diabetes demonstrates an efficient workflow for skeletal muscle proteomics, which may easily be adapted to other complex tissues.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Skeletal Muscle, Cell Culture, Muscle Cell

DISEASE(S): Obesity,Type 2 Diabetes Mellitus

SUBMITTER: atul shahaji deshmukh  

LAB HEAD: Prof. Matthias Mann

PROVIDER: PXD007697 | Pride | 2018-01-26

REPOSITORIES: Pride

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Proteomics Analysis of Skeletal Muscle from Leptin-Deficient ob/ob Mice Reveals Adaptive Remodeling of Metabolic Characteristics and Fiber Type Composition.

Schönke Milena M   Björnholm Marie M   Chibalin Alexander V AV   Zierath Juleen R JR   Deshmukh Atul S AS  

Proteomics 20180220 5-6


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  ...[more]

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