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
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