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Chronic exposure to a high-fat diet induces hepatic steatosis, impairs nitric oxide bioavailability, and modifies the mitochondrial proteome in mice.
MedLine Citation:
PMID:  20919931     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Abstract Obesity-related pathologies, such as nonalcoholic fatty liver disease, are linked to mitochondrial dysfunction and nitric oxide (NO) deficiency. Herein, we tested the hypothesis that a high-fat diet (HFD) modifies the liver mitochondrial proteome and alters proteins involved in NO metabolism, namely arginase 1 and endothelial NO synthase. Male C57BL/6 mice were fed a control or HFD and liver mitochondria were isolated for proteomics and reactive oxygen species measurements. Steatosis and hepatocyte ballooning were present in livers of HFD mice, with no pathology observed in the controls. HFD mice had increased serum glucose and decreased adiponectin. Mitochondrial reactive oxygen species was increased after 8 weeks in the HFD mice, but decreased at 16 weeks compared with the control, which was accompanied by increased uncoupling protein 2. Using proteomics, 22 proteins were altered as a consequence of the HFD. This cohort consists of oxidative phosphorylation, lipid metabolism, sulfur amino acid metabolism, and chaperone proteins. We observed a HFD-dependent increase in arginase 1 and decrease in activated endothelial NO synthase. Serum and liver nitrate + nitrite were decreased by HFD. In summary, these data demonstrate that a HFD causes steatosis, alters NO metabolism, and modifies the liver mitochondrial proteome; thus, NO may play an important role in the processes responsible for nonalcoholic fatty liver disease. Antioxid. Redox Signal. 15, 447-459.
Authors:
Heather B Eccleston; Kelly K Andringa; Angela M Betancourt; Adrienne L King; Sudheer K Mantena; Telisha M Swain; Heather N Tinsley; Ryan N Nolte; Tim R Nagy; Gary A Abrams; Shannon M Bailey
Publication Detail:
Type:  Journal Article     Date:  2011-03-31
Journal Detail:
Title:  Antioxidants & redox signaling     Volume:  15     ISSN:  1557-7716     ISO Abbreviation:  Antioxid. Redox Signal.     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-06-21     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100888899     Medline TA:  Antioxid Redox Signal     Country:  United States    
Other Details:
Languages:  eng     Pagination:  447-59     Citation Subset:  IM    
Affiliation:
1 Department of Environmental Health Sciences, University of Alabama at Birmingham , Birmingham, Alabama.
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