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Obesity-Induced Lysine Acetylation Increases Cardiac Fatty Acid Oxidation 3 and Impairs Insulin Signaling.
MedLine Citation:
PMID:  24966184     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
AIMS: Lysine acetylation is a novel post-translational pathway that regulates the activities of enzymes involved in both fatty acids and glucose metabolism. We examined whether lysine acetylation controls heart glucose and fatty acid oxidation in high fat diet (HFD) obese and SIRT3 KO mice.
METHODS AND RESULTS: C57BL/6 mice were placed on either a HFD (60% fat) or low fat diet (LFD) (4% fat) for 16- or 18-wk. Cardiac fatty acid oxidation rates were significantly increased in HFD vs LFD mice (845±76 vs 551±87 nmol.g dry wt(-1).min(-1), p<0.05). Activities of the fatty acid oxidation enzymes, long chain acyl CoA dehydrogenase (LCAD) and β-hydroxyacyl CoA dehydrogenase (β-HAD) were increased in hearts from HFD vs LFD mice, and were associated with LCAD and β-HAD hyperacetylation. Cardiac protein hyperacetylation in HFD fed mice was associated with a decrease in SIRT3 expression, while expression of the mitochondrial acetylase, GCN5L1, did not change. Interestingly, SIRT3 deletion in mice also led to an increase in cardiac fatty acid oxidation compared to WT mice (422±29 vs 291±17 nmol.g dry wt(-1).min(-1), p<0.05). Cardiac lysine acetylation was increased in SIRT3 KO mice compared to WT, including increased acetylation and activity of LCAD and β-HAD. Although the HFD and SIRT3 deletion decreased glucose oxidation, pyruvate dehydrogenase (PDH) acetylation was unaltered. However, the HFD did increase Akt acetylation, while decreasing its phosphorylation and activity.
CONCLUSION: We conclude that increased cardiac fatty acid oxidation in response to high fat feeding is controlled, in part, via the downregulation of SIRT3 and concomitant increased acetylation of mitochondrial β-oxidation enzymes.
Authors:
Osama Abo Alrob; Sowndramalingam Sankaralingam; Cary Ma; Cory S Wagg; Natasha Fillmore; Jagdip S Jaswal; Michael N Sack; Richard Lehner; Mahesh P Gupta; Evangelos D Michelakis; Raj S Padwal; David E Johnstone; Arya M Sharma; Gary D Lopaschuk
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-6-25
Journal Detail:
Title:  Cardiovascular research     Volume:  -     ISSN:  1755-3245     ISO Abbreviation:  Cardiovasc. Res.     Publication Date:  2014 Jun 
Date Detail:
Created Date:  2014-6-26     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0077427     Medline TA:  Cardiovasc Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.
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