期刊
PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS
卷 88, 期 1, 页码 71-77出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.plefa.2012.04.009
关键词
Lipotoxicity; Insulin resistance; CD36; Vesicle-associated membrane protein
资金
- Dutch Diabetes Research Foundation [2006.00.044]
- CTMM, the Center for Translational Molecular Medicine, Project PREDICCt [01C-104]
- Netherlands Heart Foundation
- Dutch Diabetes Research Foundation
- Dutch Kidney Foundation
The fatty acid transporter and scavenger receptor CD36 is increasingly being implicated in the pathogenesis of insulin resistance and its progression towards type 2 diabetes and associated cardiovascular complications. The redistribution of CD36 from intracellular stores to the plasma membrane is one of the earliest changes occurring in the heart during diet induced obesity and insulin resistance. This elicits an increased rate of fatty acid uptake and enhanced incorporation into triacylglycerol stores and lipid intermediates to subsequently interfere with insulin-induced GLUT4 recruitment (i.e., insulin resistance). In the present paper we discuss the potential of CD36 to serve as a target to rectify abnormal myocardial fatty acid uptake rates in cardiac lipotoxic diseases. Two approaches are described: (i) immunochemical inhibition of CD36 present at the sarcolemma and (ii) interference with the subcellular recycling of CD36. Using in vitro model systems of high-fat diet induced insulin resistance, the results indicate the feasibility of using CD36 as a target for adaptation of cardiac metabolic substrate utilization. In conclusion, CD36 deserves further attention as a promising therapeutic target to redirect fatty acid fluxes in the body. (c) 2012 Elsevier Ltd. All rights reserved.
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