| Increased CD36 expression in middle-aged mice contributes to obesity-related cardiac hypertrophy in the absence of cardiac dysfunction. | |
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MedLine Citation:
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PMID: 21387178 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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As aging is a significant risk factor for the development of left ventricular hypertrophy and cardiovascular disease, we hypothesized that hearts from middle-aged mice may be more sensitive to the effects of a high fat (HF) diet than hearts from young mice. To investigate this, young (10-12 week old) and middle-aged (40-44 week old) male mice were fed a low fat (LF) or HF diet (10 or 60 kcal% fat, respectively) for 12 weeks. Following this 12-week period, we show that CD36 protein expression was not changed in hearts from young mice yet was increased 1.5-fold in the middle-aged HF group compared with LF-fed age-matched counterparts. Correlated with increased CD36 expression, middle-aged mice displayed a greater degree of cardiac hypertrophy compared with young mice when fed a HF diet, and this was observed in the absence of cardiac dysfunction. Furthermore, middle-aged CD36 knockout mice were protected against HF diet-induced cardiac hypertrophy, supporting a link between CD36 and cardiac hypertrophy. To further explore potential mechanisms that may explain why middle-aged mice are more susceptible to HF diet-induced cardiac hypertrophy, we investigated mediators of cardiac growth. We show that myocardial ceramide levels were significantly increased in middle-aged mice fed a HF diet compared with LF-fed controls, which was also correlated with inhibition of AMP-activated protein kinase (AMPK). Consistent with AMPK being a negative regulator of cardiac hypertrophy, decreased AMPK activity also resulted in the activation of the mTOR/p70S6K pathway, which is known to enhance protein synthesis associated with cardiac hypertrophy. Together, these data suggest that increased myocardial CD36 expression in hearts from middle-aged mice may contribute to HF diet-induced cardiac hypertrophy and that this may be mediated by elevated ceramide levels signaling through AMPK. Overall, we suggest that inhibition of CD36-mediated fatty acid uptake may prevent obesity-related cardiomyopathies in the middle-aged population. |
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Authors:
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Miranda M Y Sung; Debby P Y Koonen; Carrie-Lynn M Soltys; René L Jacobs; Maria Febbraio; Jason R B Dyck |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-3-10 |
Journal Detail:
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Title: Journal of molecular medicine (Berlin, Germany) Volume: - ISSN: 1432-1440 ISO Abbreviation: - Publication Date: 2011 Mar |
Date Detail:
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Created Date: 2011-3-9 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9504370 Medline TA: J Mol Med Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Cardiovascular Research Centre, Department of Pediatrics, University of Alberta, Edmonton, AB, Canada. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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