Document Detail

Relationship of glucose and oleate metabolism to cardiac function in lipin-1 deficient (fld) mice.
MedLine Citation:
PMID:  22058427     Owner:  NLM     Status:  MEDLINE    
Lipin-1 is the major phosphatidate phosphatase (PAP) in the heart and a transcriptional coactivator that regulates fatty acid (FA) oxidation in the liver. As the control of FA metabolism is essential for maintaining cardiac function, we investigated whether lipin-1 deficiency affects cardiac metabolism and performance. Cardiac PAP activity in lipin-1 deficient [fatty liver dystrophy (fld)] mice was decreased by >80% compared with controls. Surprisingly, oleate oxidation and incorporation in triacylglycerol (TG), as well as glucose oxidation, were not significantly different in perfused working fld hearts. Despite this, [³H]oleate accumulation in phosphatidate and phosphatidylinositol was increased in fld hearts, reflecting the decreased PAP activity. Phosphatidate accumulation was linked to increased cardiac mammalian target of rapamycin complex 1 (mTORC1) signaling and endoplasmic reticulum (ER) stress. Transthoracic echocardiography showed decreased cardiac function in fld mice; however, cardiac dysfunction was not observed in ex vivo perfused working fld hearts. This showed that changes in systemic factors due to the global absence of lipin-1 could contribute to the decreased cardiac function in vivo. Collectively, this study shows that fld hearts exhibit unchanged oleate esterification, as well as oleate and glucose oxidation, despite the absence of lipin-1. However, lipin-1 deficiency increases the accumulation of newly synthesized phosphatidate and induces aberrant cell signaling.
Bernard P C Kok; Petra C Kienesberger; Jason R B Dyck; David N Brindley
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-11-05
Journal Detail:
Title:  Journal of lipid research     Volume:  53     ISSN:  0022-2275     ISO Abbreviation:  J. Lipid Res.     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2011-12-16     Completed Date:  2012-04-09     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  0376606     Medline TA:  J Lipid Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  105-18     Citation Subset:  IM    
Signal Transduction Research Group, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada.
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MeSH Terms
Fatty Liver / physiopathology
Glucose / metabolism*
Heart / physiology*
Myocardium / metabolism
Nuclear Proteins / deficiency*
Oleic Acid / metabolism*
Phosphatidate Phosphatase / deficiency*
Triglycerides / biosynthesis
Grant Support
//Canadian Institutes of Health Research
Reg. No./Substance:
0/Nuclear Proteins; 0/Triglycerides; 112-80-1/Oleic Acid; 50-99-7/Glucose; EC protein, mouse; EC Phosphatase

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