Activity-based protein profiling reveals mitochondrial oxidative enzyme impairment and restoration in diet-induced obese mice.
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...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3480472?pdf=render |
| _version_ | 1819268060403466240 |
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| author | Natalie C Sadler Thomas E Angel Michael P Lewis Leeanna M Pederson Lacie M Chauvigné-Hines Susan D Wiedner Erika M Zink Richard D Smith Aaron T Wright |
| author_facet | Natalie C Sadler Thomas E Angel Michael P Lewis Leeanna M Pederson Lacie M Chauvigné-Hines Susan D Wiedner Erika M Zink Richard D Smith Aaron T Wright |
| author_sort | Natalie C Sadler |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-23T21:27:03Z |
| format | Article |
| id | doaj.art-c06d9f4157e64aedb65e641b732f8928 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-23T21:27:03Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-c06d9f4157e64aedb65e641b732f89282022-12-21T17:30:34ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-01710e4799610.1371/journal.pone.0047996Activity-based protein profiling reveals mitochondrial oxidative enzyme impairment and restoration in diet-induced obese mice.Natalie C SadlerThomas E AngelMichael P LewisLeeanna M PedersonLacie M Chauvigné-HinesSusan D WiednerErika M ZinkRichard D SmithAaron T WrightHigh-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.http://europepmc.org/articles/PMC3480472?pdf=render |
| spellingShingle | Natalie C Sadler Thomas E Angel Michael P Lewis Leeanna M Pederson Lacie M Chauvigné-Hines Susan D Wiedner Erika M Zink Richard D Smith Aaron T Wright Activity-based protein profiling reveals mitochondrial oxidative enzyme impairment and restoration in diet-induced obese mice. PLoS ONE |
| title | Activity-based protein profiling reveals mitochondrial oxidative enzyme impairment and restoration in diet-induced obese mice. |
| title_full | Activity-based protein profiling reveals mitochondrial oxidative enzyme impairment and restoration in diet-induced obese mice. |
| title_fullStr | Activity-based protein profiling reveals mitochondrial oxidative enzyme impairment and restoration in diet-induced obese mice. |
| title_full_unstemmed | Activity-based protein profiling reveals mitochondrial oxidative enzyme impairment and restoration in diet-induced obese mice. |
| title_short | Activity-based protein profiling reveals mitochondrial oxidative enzyme impairment and restoration in diet-induced obese mice. |
| title_sort | activity based protein profiling reveals mitochondrial oxidative enzyme impairment and restoration in diet induced obese mice |
| url | http://europepmc.org/articles/PMC3480472?pdf=render |
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