The DOI matches its Crossref record; 57 of the 57 references it cites were found in a registry or an index.
CD36 Deficiency Rescues Lipotoxic Cardiomyopathy
Abstract
Obesity-related diabetes mellitus leads to increased myocardial uptake of fatty acids (FAs), resulting in a form of cardiac dysfunction referred to as lipotoxic cardiomyopathy. We have shown previously that chronic activation of the FA-activated nuclear receptor, peroxisome proliferator-activated receptor α (PPARα), is sufficient to drive the metabolic and functional abnormalities of the diabetic heart. Mice with cardiac-restricted overexpression of PPARα (myosin heavy chain [MHC]-PPARα) exhibit myocyte lipid accumulation and cardiac dysfunction. We sought to define the role of the long-chain FA transporter CD36 in the pathophysiology of lipotoxic forms of cardiomyopathy. MHC-PPARα mice were crossed with CD36-deficient mice (MHC-PPARα/CD36 −/− mice). The absence of CD36 prevented myocyte triacylglyceride accumulation and cardiac dysfunction in the MHC-PPARα mice under basal conditions and following administration of high-fat diet. Surprisingly, the rescue of the MHC-PPARα phenotype by CD36 deficiency was associated with increased glucose uptake and oxidation rather than changes in FA utilization. As predicted by the metabolic changes, the activation of PPARα target genes involved in myocardial FA-oxidation pathways in the hearts of the MHC-PPARα mice was unchanged in the CD36-deficient background. However, PPARα-mediated suppression of genes involved in glucose uptake and oxidation was reversed in the MHC-PPARα/ CD36 −/− mice. We conclude that CD36 is necessary for the development of lipotoxic cardiomyopathy in MHC-PPARα mice and that novel therapeutic strategies aimed at reducing CD36-mediated FA uptake show promise for the prevention or treatment of cardiac dysfunction related to obesity and diabetes.
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“Indeed, genetic ablation of expression of the FA transporter (CD36) reversed lipotoxicity in PPAR-α overexpressing mice (382).”
From Cardiac remodeling in obesity (2008) · cites this paper as [382]
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Cites
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Peroxisome Proliferator-Activated Receptors: Nuclear Control of Metabolism
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Myocardial Substrate Metabolism in the Normal and Failing Heart
Stanley, W. C., Recchia, F. A., & Lopaschuk, G. D. (2005) · Physiological Reviews · doi:10.1152/physrev.00006.2004 · Cited by 2,095
New type of cardiomyopathy associated with diabetic glomerulosclerosis
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“Lipotoxic cardiomyopathy has been described in animal models of obesity and diabetes.15,16 In addition, humans with inborn errors in mitochondrial FA oxidation also develop cardiomyopathy associated with myocyte lipid accumulation.42 Proposed mechanisms for the development of cardiac dysfunction secondary to myocyte l…”
BackgroundPGC-1 coactivators: inducible regulators of energy metabolism in health and disease
Finck, B. N. (2006) · Journal of Clinical Investigation · doi:10.1172/jci27794 · Cited by 1,461
Self-citationLipotoxic heart disease in obese rats: Implications for human obesity
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Self-citationThe cardiac phenotype induced by PPARα overexpression mimics that caused by diabetes mellitus
Finck, B. N., Lehman, J. J., Leone, T. C., Welch, M. J., Bennett, M. J., Kovács, A. D., Han, X., Gross, R. W., Kozak, R., Lopaschuk, G. D., et al. (2002) · Journal of Clinical Investigation · doi:10.1172/jci14080 · Cited by 887
Self-citationExpression cloning and characterization of a novel adipocyte long chain fatty acid transport protein
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Cited by
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Myocardial Fatty Acid Metabolism in Health and Disease
Lopaschuk, G. D., Ussher, J. R., Folmes, C. D. L., Jaswal, J. S., & Stanley, W. C. (2010) · Physiological Reviews · doi:10.1152/physrev.00015.2009 · Cited by 2,228
Jia, G., Hill, M. A., & Sowers, J. R. (2018) · Circulation Research · doi:10.1161/circresaha.117.311586 · Cited by 1,872
Diabetic Cardiomyopathy Revisited
Boudina, S., & Abel, E. D. (2007) · Circulation · doi:10.1161/circulationaha.106.679597 · Cited by 1,543
CD36, a Scavenger Receptor Involved in Immunity, Metabolism, Angiogenesis, and Behavior
Silverstein, R. L., & Febbraio, M. (2009) · Science Signaling · doi:10.1126/scisignal.272re3 · Cited by 1,141
Self-citationTan, Y., Zhang, Z., Zheng, C., Wintergerst, K. A., Keller, B. B., & Cai, L. (2020) · Nature Reviews Cardiology · doi:10.1038/s41569-020-0339-2 · Cited by 862
Metadata
- Authors
- Yang, J., Sambandam, N., Han, X., Gross, R. W., Courtois, M., Kovacs, A., Febbraio, M., Finck, B. N., & Kelly, D. P.
- Affiliations
- Cleveland Clinic (US)
- From the Center for Cardiovascular Research (J.Y., N.S., R.W.G., M.C., A.K., D.P.K.) and Departments of Medicine (J.Y., N.S., X.H., R.W.G., M.C., A.K., B.N.F., D.P.K.), Molecular Biology & Pharmacology (R.W.G., D.P.K.), and Pediatrics (D.P.K.), Washington University School of Medicine, St Louis, Mo; and Department of Cell Biology (M.F.), Lerner Research Institute, Cleveland Clinic, Ohio.
- Venue
- Circulation Research
- Published
- 2007-04-27
- Volume
- 100
- Issue
- 8
- Pages
- 1208-1217
- ISSN
- 0009-7330 (ISSN-L)
- 1524-4571
- OpenAlex
- W2160476964
- Cited by
- 246
- References
- 57
- Citations by year
- 2026: 5 · 2025: 8 · 2024: 10 · 2023: 5 · 2022: 11 · 2021: 13 · 2020: 13 · 2019: 7 · 2018: 18 · 2017: 12 · 2016: 16 · 2015: 14 · 2014: 11 · 2013: 12 · 2012: 22
- FWCI
- 7.41
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Circulation Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (P01HL57278, P01HL057278, P50HL077113, K08HL076452, KO8 HL076452)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30 DK-52574, P30-DK56341, P30DK056341, P30DK052574)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Disease and Adiposity
- Keywords
- CD36, lipotoxic cardiomyopathy, PPARα, fatty acid uptake, cardiac dysfunction, triglyceride accumulation, glucose uptake, glucose oxidation, fatty acid oxidation, obesity, diabetes mellitus, myosin heavy chain, high-fat diet, myocardial lipid metabolism
- MeSH terms
- Animals, Diabetic Angiopathies, Fatty Acids, Glucose, Mice, Inbred C57BL, Mice, Transgenic, Obesity, Oxidation-Reduction, Phenotype, Mice, Knockout, CD36 Antigens, PPAR alpha, Adiposity, Mice
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