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New insights into long-chain fatty acid uptake by heart muscle: a crucial role for fatty acid translocase/CD36.

ABSTRACT: Long-chain fatty acids are an important source of energy for several cell types, in particular for the heart muscle cell. Three different proteins, fatty acid translocase (FAT)/CD36, fatty acid transport protein and plasma membrane fatty acid binding protein, have been identified as possible membrane fatty acid transporters. Much information has been accumulated recently about the fatty acid transporting function of FAT/CD36. Several experimental models to study the influence of altered FAT/CD36 expression on fatty acid homoeostasis have been identified or developed, and underscore the importance of FAT/CD36 for adequate fatty acid transport. These models include the FAT/CD36 null mouse, the spontaneously hypertensive rat and FAT/CD36-deficient humans. The fatty acid transporting role of FAT/CD36 is further demonstrated in mice overexpressing muscle-specific FAT/CD36, and in transgenic mice generated using a genetic-rescue approach. In addition, a wealth of information has been gathered about the mechanisms that regulate FAT/CD36 gene expression and the presence of functional FAT/CD36 on the plasma membrane. Available data also indicate that FAT/CD36 may have an important role in the aetiology of cardiac disease, especially cardiac hypertrophy and diabetic cardiomyopathy. This review discusses our current knowledge of the three candidate fatty acid transporters, the metabolic consequences of alterations in FAT/CD36 levels in different models, and the mechanisms that have been identified for FAT/CD36 regulation.

SUBMITTER: Brinkmann JF

PROVIDER: S-EPMC1222912 | biostudies-other | 2002 Nov

REPOSITORIES: biostudies-other

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Project description:The rat membrane protein fatty acid translocase (FAT), which shows sequence similarity to human CD36 (a membrane protein supposedly involved in a variety of membrane processes), is implicated in the transport of long-chain fatty acids across cellular membranes. To set up an immunoassay for quantification of FAT in different tissues, we isolated a series of anti-FAT antibodies by panning a large naive phage antibody library on FAT-transfected H9c2 cells. All seven different phage antibody fragments isolated reacted specifically with FAT, and most likely recognize the same or closely located immunodominant sites on FAT, as a competitive monoclonal antibody (mAb) (CLB-IV7) completely blocked the binding of all these phage antibodies to cells. A sandwich ELISA was set up using mAb 131. 4 (directed against purified CD36 from human platelets) as capture antibody and phage antibodies and anti-phage sera as detector. With this ELISA (sensitivity 0.05 microgram/ml), the FAT content in isolated cardiomyocytes was found to be comparable with that of total heart ( approximately 3 mg/g of protein), while liver tissue and endothelial cells were below the detection limit (<0.1 mg of FAT/g of protein). During rat heart development, protein levels of FAT rose from 1.7+/-0.7 mg/g of protein on the day before birth to 3.6+/-0.4 mg/g of protein on day 70. Comparing control with streptozotocin-induced diabetic rats, a statistically significant (P<0.05) 2-4-fold increase of FAT was seen in heart (from 4.2+/-2.3 to 11.0+/-5.7 mg/g of protein), soleus (from 0.6+/-0.1 to 1.4+/-0.5 mg/g of protein) and extensor digitorum longus (EDL) muscle (from 0.3+/-0.1 to 1. 2+/-0.8 mg/g of protein). In addition, the FAT contents of each of these muscles were found to be of similar magnitude to the contents of cytoplasmic heart-type fatty-acid-binding protein in both diabetic rats and controls, supporting the suggested roles of these two proteins in cellular fatty acid metabolism. This is the first time phage display technology has been succesfully applied for direct selection, from a large naive antibody library, of antibodies that recognize selected membrane proteins in their natural context.

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New insights into long-chain fatty acid uptake by heart muscle: a crucial role for fatty acid translocase/CD36.

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