Document Detail

Altered glutathione homeostasis in heart augments cardiac lipotoxicity associated with diet-induced obesity in mice.
MedLine Citation:
PMID:  22021075     Owner:  NLM     Status:  MEDLINE    
Obesity-related cardiac lipid accumulation is associated with increased myocardial oxidative stress. The role of the antioxidant glutathione in cardiac lipotoxicity is unclear. Cystathionine β-synthase (Cbs) catalyzes the first step in the trans-sulfuration of homocysteine to cysteine, which is estimated to provide ∼50% of cysteine for hepatic glutathione biosynthesis. As cardiac glutathione is a reflection of the liver glutathione pool, we hypothesize that mice heterozygous for targeted disruption of Cbs (Cbs(+/-)) are more susceptible to obesity-related cardiolipotoxicity because of impaired liver glutathione synthesis. Cbs(+/+) and Cbs(+/-) mice were fed a high fat diet (60% energy) from weaning for 13 weeks to induce obesity and had similar increases in body weight and body fat. This was accompanied by increased hepatic triglyceride but no differences in hepatic glutathione levels compared with mice fed chow. However, Cbs(+/-) mice with diet-induced obesity had greater glucose intolerance and lower total and reduced glutathione levels in the heart, accompanied by lower plasma cysteine levels compared with Cbs(+/+) mice. Higher triglyceride concentrations, increased oxidative stress, and increased markers of apoptosis were also observed in heart from Cbs(+/-) mice with diet-induced obesity compared with Cbs(+/+) mice. This study suggests a novel role for Cbs in maintaining the cardiac glutathione pool and protecting against cardiac lipid accumulation and oxidative stress during diet-induced obesity in mice.
Sanjoy Ghosh; Dian C Sulistyoningrum; Melissa B Glier; C Bruce Verchere; Angela M Devlin
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-10-23
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  286     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-12-05     Completed Date:  2012-02-21     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  42483-93     Citation Subset:  IM    
Department of Pathology, University of British Columbia, Vancouver, British Columbia, V5Z 4H4, Canada.
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MeSH Terms
Cystathionine beta-Synthase / genetics
Cysteine / blood
Disease Models, Animal
Glutathione / metabolism*
Heart / physiology
Liver / metabolism
Mice, Inbred C57BL
Mice, Transgenic
Obesity / metabolism*
Grant Support
//Canadian Institutes of Health Research
Reg. No./Substance:
52-90-4/Cysteine; 70-18-8/Glutathione; EC beta-Synthase

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