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Title: Activity-Based Protein Profiling Reveals Mitochondrial Oxidative Enzyme Impairment and Restoration in Diet-Induced Obese Mice

Abstract

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 the 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.

Authors:
; ; ; ; ; ; ; ;
Publication Date:
Research Org.:
Pacific Northwest National Laboratory (PNNL), Richland, WA (US), Environmental Molecular Sciences Laboratory (EMSL)
Sponsoring Org.:
USDOE
OSTI Identifier:
1057356
Report Number(s):
PNNL-SA-88011
47292
DOE Contract Number:  
AC05-76RL01830
Resource Type:
Journal Article
Journal Name:
PLoS One, 7(10):Article No. e47996
Additional Journal Information:
Journal Name: PLoS One, 7(10):Article No. e47996
Country of Publication:
United States
Language:
English
Subject:
Environmental Molecular Sciences Laboratory

Citation Formats

Sadler, Natalie C., Angel, Thomas E., Lewis, Michael P., Pederson, Leeanna M., Chauvigne-Hines, Lacie M., Wiedner, Susan D., Zink, Erika M., Smith, Richard D., and Wright, Aaron T. Activity-Based Protein Profiling Reveals Mitochondrial Oxidative Enzyme Impairment and Restoration in Diet-Induced Obese Mice. United States: N. p., 2012. Web. doi:10.1371/journal.pone.0047996.
Sadler, Natalie C., Angel, Thomas E., Lewis, Michael P., Pederson, Leeanna M., Chauvigne-Hines, Lacie M., Wiedner, Susan D., Zink, Erika M., Smith, Richard D., & Wright, Aaron T. Activity-Based Protein Profiling Reveals Mitochondrial Oxidative Enzyme Impairment and Restoration in Diet-Induced Obese Mice. United States. doi:10.1371/journal.pone.0047996.
Sadler, Natalie C., Angel, Thomas E., Lewis, Michael P., Pederson, Leeanna M., Chauvigne-Hines, Lacie M., Wiedner, Susan D., Zink, Erika M., Smith, Richard D., and Wright, Aaron T. Wed . "Activity-Based Protein Profiling Reveals Mitochondrial Oxidative Enzyme Impairment and Restoration in Diet-Induced Obese Mice". United States. doi:10.1371/journal.pone.0047996.
@article{osti_1057356,
title = {Activity-Based Protein Profiling Reveals Mitochondrial Oxidative Enzyme Impairment and Restoration in Diet-Induced Obese Mice},
author = {Sadler, Natalie C. and Angel, Thomas E. and Lewis, Michael P. and Pederson, Leeanna M. and Chauvigne-Hines, Lacie M. and Wiedner, Susan D. and Zink, Erika M. and Smith, Richard D. and Wright, Aaron T.},
abstractNote = {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 the 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.},
doi = {10.1371/journal.pone.0047996},
journal = {PLoS One, 7(10):Article No. e47996},
number = ,
volume = ,
place = {United States},
year = {2012},
month = {10}
}