| Cyclic GMP signaling in cardiomyocytes modulates fatty acid trafficking and prevents triglyceride accumulation. | |
| | |
MedLine Citation:
|
PMID: 18590915 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
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. |
| | |
Authors:
|
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
:
|
5472165 - Differences between manganese and magnesium ions with regard to fatty acid biosynthesis... 7608065 - Purification of a malonyltransferase from streptomyces coelicolor a3(2) and analysis of... 1778415 - Synthesis of 3-furylmethylpenicillin using an enzymatic procedure. 7622515 - Discovery of an epidermal stearoyl-acyl carrier protein thioesterase. its potential rol... 5472165 - Differences between manganese and magnesium ions with regard to fatty acid biosynthesis... 8855145 - Standardization of pyridinium crosslinks, pyridinoline and deoxypyridinoline, for use a... |
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 |
Affiliation:
|
Montreal Heart Institute, University of Montreal, Montreal, Quebec, Canada. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Acetyl Coenzyme A
/
metabolism Animals Biological Transport, Active / physiology Cyclic GMP / physiology* Fatty Acids / metabolism* Glycolysis / physiology Male Mice Mice, Inbred C57BL Mice, Transgenic Myocytes, Cardiac / metabolism*, physiology Oleic Acid / metabolism Signal Transduction / physiology* Triglycerides / antagonists & inhibitors*, metabolism* |
| Grant Support | |
ID/Acronym/Agency:
|
77791//Canadian Institutes of Health Research; HL-074259/HL/NHLBI NIH HHS |
| Chemical | |
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.