Up-regulation of CD36/FAT in preadipocytes in familial combined hyperlipidemia

Laboratory of Molecular Metabolism and Endocrinology, Department of Internal Medicine, Maastricht, The Netherlands.
The FASEB Journal (Impact Factor: 5.04). 01/2006; 19(14):2063-5. DOI: 10.1096/fj.04-2403fje
Source: PubMed


Familial combined hyperlipidemia (FCHL) shows many features of the metabolic syndrome. The strong genetic component makes it an excellent model to study the genetic background of metabolic syndrome and insulin resistance. Adipose tissue is believed to contribute to, or even underlie, the FCHL phenotype and is an interesting target tissue for gene expression studies. However, interpretation of adipose tissue gene expression experiments is complex since expression differences cannot only arise as a direct consequence of a genetic trait, but may also reflect an adaptation to metabolic influences at the cellular level. In the present study, we measured gene expression levels in cultured primary human preadipocytes from FCHL and control subjects. Since isolated preadipocytes were allowed to replicate for weeks under standardized conditions, the contribution of previous metabolic influences is rather small whereas genetic defects are preserved and expressed in vitro. The main finding was up-regulation of CD36/FAT in FCHL preadipocytes, confirmed in two independent groups of subjects, and a concomitant increase in CD36/FAT-mediated fatty acid uptake. CD36/FAT overexpression has previously been shown to be associated with other insulin-resistant states. The present data suggest that CD36/FAT overexpression in FCHL occurs very early in adipocyte differentiation and may be of genetic origin.

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    • "The results of subsequent studies on CD36 gene polymorphisms suggested the association between these genetic variants and altered serum lipids and also impaired glucose metabolism (Lepretre et al., 2004; Meex et al., 2005; Morii et al., 2009). Because of the prevalence of MetS in Iran (32.1% in adults) (Zabetian et al., 2007) and the absence of association studies on CD36 gene in our population, this study was designed to examine the association of rs10499859A > G and rs13246513C > T polymorphisms with the MetS and its components . "
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    • "For example, Fyn was reported to be the kinase responsible for 3T3L1 adipocyte insulin-stimulated caveolin tyrosine phosphorylation and to associate with lipid raft proteins flotilin and CD36 (Bull et al., 1994; Huang et al., 1991; Mastick and Saltiel, 1997). In this regard, CD36, also known as FAT (Fatty Acid Translocase), facilitates long-chain fatty acid uptake in skeletal muscle and adipose tissue and is linked to phenotypic features of the metabolic syndrome, including insulin resistance and dyslipidemia (Drover and Abumrad, 2005; Drover et al., 2005; Meex et al., 2005; Pravenec et al., 2003). Thus, the physical association of Fyn with CD36 further suggests a functional coupling between lipid raft organization and the regulation of fatty acid translocation and potentially fatty acid metabolism. "
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