Document Detail

Cyclic GMP signaling in cardiomyocytes modulates fatty acid trafficking and prevents triglyceride accumulation.
MedLine Citation:
PMID:  18590915     Owner:  NLM     Status:  MEDLINE    
While the balance between carbohydrates and fatty acids for energy production appears to be crucial for cardiac homeostasis, much remains to be learned about the molecular mechanisms underlying this relationship. Given the reported benefits of cGMP signaling on the myocardium, we investigated the impact of its chronic activation on cardiac energy metabolism using mice overexpressing a constitutively active cytoplasmic guanylate cyclase (GC(+/0)) in cardiomyocytes. Ex vivo working GC(+/0) heart perfusions with (13)C-labeled substrates revealed an altered pattern of exogenous substrate fuel selection compared to controls, namely a 38+/-9% lower contribution of exogenous fatty acids to acetyl-CoA formation, while that of carbohydrates remains unchanged despite a two-fold increase in glycolysis. The lower contribution of exogenous fatty acids to energy production is not associated with changes in energy demand or supply (contractile function, oxygen consumption, tissue acetyl-CoA or CoA levels, citric acid cycle flux rate) or in the regulation of beta-oxidation (acetyl-CoA carboxylase activity, tissue malonyl-CoA levels). However, GC(+/0) hearts show a two-fold increase in the incorporation of exogenous oleate into triglycerides. Furthermore, the following molecular data are consistent with a concomitant increase in triglyceride hydrolysis: (i) increased abundance of hormone sensitive lipase (HSL) protein (24+/-11%) and mRNA (22+/-4%) as well as (ii) several phosphorylation events related to HSL inhibitory (AMPK) and activation (ERK 1/2) sites, which should contribute to enhance its activity. These changes in exogenous fatty acid trafficking in GC(+/0) hearts appear to be functionally relevant, as demonstrated by their resistance to fasting-induced triglyceride accumulation. While the documented metabolic profile of GC(+/0) mouse hearts is partly reminiscent of hypertrophied hearts, the observed changes in lipid trafficking have not been previously documented, and may be part of the molecular mechanism underlying the benefits of cGMP signaling on the myocardium.
Ramzi J Khairallah; Maya Khairallah; Roselle Gélinas; Bertrand Bouchard; Martin E Young; Bruce G Allen; Gary D Lopaschuk; Christian F Deschepper; Christine Des Rosiers
Related Documents :
8593485 - Stereospecific taurine conjugation of the trans-oh metabolite (active metabolite) of cs...
11876265 - Regulation of phosphatidic acid phosphohydrolase 1 by fatty acids.
3511845 - Enzymatic bases for the fatty acid positioning in phospholipids of brevibacterium ammon...
6731835 - Determination of malonyl-coenzyme a in rat heart, kidney, and liver: a comparison betwe...
15894855 - A suicide using a homemade carbon monoxide "death machine".
310855 - Characterization of lipopolysaccharide of haemophilus influenzae.
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2008-05-27
Journal Detail:
Title:  Journal of molecular and cellular cardiology     Volume:  45     ISSN:  1095-8584     ISO Abbreviation:  J. Mol. Cell. Cardiol.     Publication Date:  2008 Aug 
Date Detail:
Created Date:  2008-08-15     Completed Date:  2008-11-07     Revised Date:  2010-10-04    
Medline Journal Info:
Nlm Unique ID:  0262322     Medline TA:  J Mol Cell Cardiol     Country:  England    
Other Details:
Languages:  eng     Pagination:  230-9     Citation Subset:  IM    
Montreal Heart Institute, University of Montreal, Montreal, Quebec, Canada.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Acetyl Coenzyme A / metabolism
Biological Transport, Active / physiology
Cyclic GMP / physiology*
Fatty Acids / metabolism*
Glycolysis / physiology
Mice, Inbred C57BL
Mice, Transgenic
Myocytes, Cardiac / metabolism*,  physiology
Oleic Acid / metabolism
Signal Transduction / physiology*
Triglycerides / antagonists & inhibitors*,  metabolism*
Grant Support
77791//Canadian Institutes of Health Research; HL-074259/HL/NHLBI NIH HHS
Reg. No./Substance:
0/Fatty Acids; 0/Triglycerides; 112-80-1/Oleic Acid; 72-89-9/Acetyl Coenzyme A; 7665-99-8/Cyclic GMP

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Cytopathological process by multiple nucleopolyhedrovirus in the testis of Bombyx mori L., 1758 (Lep...
Next Document:  Substance use disorders and suicide attempts in bipolar subtypes.