title: Up-regulation of CD36/FAT in preadipocytes in familial combined hyperlipidemia.
abstract: 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.
authors.affiliation: Laboratory of Molecular Metabolism and Endocrinology, Department of Internal Medicine, Maastricht, The Netherlands. steven.meex@intmed.unimaas.nl
authors.forename: Steven J R
authors.initials: SJ
authors.lastname: Meex
authors.forename: Carla J H
authors.initials: CJ
authors.lastname: van der Kallen
authors.forename: Marleen M J
authors.initials: MM
authors.lastname: van Greevenbroek
authors.forename: Petra M H
authors.initials: PM
authors.lastname: Eurlings
authors.forename: Mohammed
authors.initials: M
authors.lastname: El Hasnaoui
authors.forename: Chris T A
authors.initials: CT
authors.lastname: Evelo
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Lindsey
authors.forename: Joost J F P
authors.initials: JJ
authors.lastname: Luiken
authors.forename: Jan F C
authors.initials: JF
authors.lastname: Glatz
authors.forename: Tjerk W A
authors.initials: TW
authors.lastname: de Bruin
mesh_terms: D017667:Adipocytes / Q000166:cytology*; D000273:Adipose Tissue / Q000473:pathology; D000328:Adult; D015992:Body Mass Index; D018955:CD36 Antigens / Q000096:biosynthesis*; D002454:Cell Differentiation; D003001:Cloning, Molecular; D017931:DNA Primers / Q000737:chemistry; D015536:Down-Regulation; D020224:Expressed Sequence Tags; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D015723:Gene Library; D006801:Humans; D006950:Hyperlipidemia, Familial Combined / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D007333:Insulin Resistance; D008055:Lipids / Q000737:chemistry; D008297:Male; D024821:Metabolic Syndrome / Q000378:metabolism; D008875:Middle Aged; D008954:Models, Biological; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
chemical_list: D018955:CD36 Antigens; D017931:DNA Primers; D005227:Fatty Acids; D008055:Lipids; D012333:RNA, Messenger