Activity-Based Protein Profiling Reveals Mitochondrial Oxidative Enzyme Impairment and Restoration in Diet-Induced Obese Mice
| Autor: | Richard D. Smith, Thomas E. Angel, Michael P. Lewis, Natalie C. Sadler, Erika M. Zink, LeeAnna M. Pederson, Aaron T. Wright, Lacie M. Chauvigné-Hines, Susan D. Wiedner |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Male
Proteomics Time Factors Proteome Mouse Respiratory chain lcsh:Medicine Mitochondrion Biochemistry Mass Spectrometry Oxidative Phosphorylation Mice Adenosine Triphosphate Endocrinology 0302 clinical medicine lcsh:Science 2. Zero hunger 0303 health sciences Multidisciplinary Molecular Structure Enzyme Classes Systems Biology digestive oral and skin physiology food and beverages Animal Models Enzymes Chemistry medicine.anatomical_structure Medicine Metabolic Pathways Oxidation-Reduction Research Article medicine.medical_specialty Citric Acid Cycle 030209 endocrinology & metabolism Citrate (si)-Synthase Oxidative phosphorylation Biology Diet High-Fat Peptide Mapping Electron Transport Complex IV Mitochondrial Proteins Enzyme Regulation 03 medical and health sciences Model Organisms Insulin resistance Internal medicine Chemical Biology medicine Animals Obesity Muscle Skeletal 030304 developmental biology Diabetic Endocrinology Organic Chemistry Organic Synthesis lcsh:R nutritional and metabolic diseases Skeletal muscle Lipid metabolism Diabetes Mellitus Type 2 Lipid Metabolism medicine.disease Mitochondria Muscle Mice Inbred C57BL Citric acid cycle Metabolism lcsh:Q Diet-induced obese Protein Abundance Chromatography Liquid |
| Zdroj: | PLoS ONE, Vol 7, Iss 10, p e47996 (2012) PLoS ONE |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0047996 |
| Popis: | High-fat diet (HFD) induced obesity and concomitant development of insulin resistance (IR) and type 2 diabetes mellitus have been linked to mitochondrial dysfunction. However, it is not clear whether mitochondrial dysfunction is a direct effect of a HFD, or if mitochondrial function is reduced with increased HFD duration. We hypothesized that the function of mitochondrial oxidative and lipid metabolism functions in skeletal muscle mitochondria for HFD mice are similar, or elevated, relative to standard diet (SD) mice; thereby, IR is neither cause nor consequence of mitochondrial dysfunction. We applied a chemical probe approach to identify functionally reactive ATPases and nucleotide-binding proteins in mitochondria isolated from skeletal muscle of C57Bl/6J mice fed HFD or SD chow for 2-, 8-, or 16-weeks; feeding time points known to induce IR. A total of 293 probe-labeled proteins were identified by mass spectrometry-based proteomics, of which 54 differed in abundance between HFD and SD mice. We found proteins associated with the TCA cycle, oxidative phosphorylation (OXPHOS), and lipid metabolism were altered in function when comparing SD to HFD fed mice at 2-weeks, however by 16-weeks HFD mice had TCA cycle, β-oxidation, and respiratory chain function at levels similar to or higher than SD mice. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|