Meex Steven J R, van der Kallen Carla J H, van Greevenbroek Marleen M J, Eurlings Petra M H, El Hasnaoui Mohammed, Evelo Chris T A, Lindsey Patrick J, Luiken Joost J F P, Glatz Jan F C, de Bruin Tjerk W A
Laboratory of Molecular Metabolism and Endocrinology, Department of Internal Medicine, Maastricht, The Netherlands.
FASEB J. 2005 Dec;19(14):2063-5. doi: 10.1096/fj.04-2403fje. Epub 2005 Oct 11.
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.
家族性混合性高脂血症（FCHL）具有代谢综合征的许多特征。强大的遗传因素使其成为研究代谢综合征和胰岛素抵抗遗传背景的理想模型。脂肪组织被认为与FCHL表型有关，甚至是其基础，并且是基因表达研究中一个有趣的靶组织。然而，脂肪组织基因表达实验的解释很复杂，因为表达差异不仅可能是遗传特征的直接结果，还可能反映细胞水平对代谢影响的适应性。在本研究中，我们测量了来自FCHL患者和对照受试者的原代培养人前脂肪细胞中的基因表达水平。由于分离的前脂肪细胞在标准化条件下可复制数周，先前代谢影响的作用相当小，而遗传缺陷在体外得以保留并表达。主要发现是FCHL前脂肪细胞中CD36/FAT上调，在两组独立受试者中得到证实，并且CD36/FAT介导的脂肪酸摄取随之增加。先前已表明CD36/FAT过表达与其他胰岛素抵抗状态有关。目前的数据表明，FCHL中CD36/FAT过表达在脂肪细胞分化的早期就已出现，并且可能源于遗传。
