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* Cardiovascular Research Institute Maastricht, Laboratory of Molecular Metabolism and Endocrinology, Department of Internal Medicine, University of Maastricht, Maastricht, The Netherlands
Department of Plastic Surgery, Academic Hospital Maastricht, The Netherlands
1 To whom correspondence should be addressed. e-mail: tdb{at}sint.azm.nl
Subjects with familial combined hyperlipidemia (FCHL) are characterized by a complex metabolic phenotype with hyperlipidemia, insulin resistance, and central obesity. FCHL is due to impaired adipose tissue function superimposed on hepatic overproduction of lipoproteins. We investigated adipose tissue as an interesting target tissue for differential gene expression in FCHL. Human cDNA expression array analyses, in which adipose tissue from five FCHL patients was compared with that from four age, gender, and BMI matched controls, resulted in the identification of 22 up-regulated and three down-regulated genes. The genes differentially expressed imply activation of the adipocyte cell cycle genes. Furthermore, the differential expression of the genes coding for tumor necrosis factor
, interleukin 6, and intracellular adhesion molecule 1 support a role for adipose tissue in insulin resistance in FCHL subjects.
The observed changes represent a primary genetic defect, an adaptive response, or a contribution of both.
Abbreviations: apo, apolipoprotein; BMI, body mass index; CAD, coronary artery disease; CCDN1, G1/S-specific cyclin D1; CCDN2, G1/S-specific cyclin D2; CDKN1A, cyclin-dependent kinase inhibitor 1A; ERBB3, v-erb-b2 erythroblastic leukemia viral oncogen homolog 3; FCHL, familial combined hyperlipidemia; GADD45, DNA damage-inducible gene GADD45; ICAM1, intracellular adhesion molecule 1; ID1, DNA binding protein inhibitor ID1; IFNGR2, interferon gamma receptor 2; IL-6, interleukin 6; KRBH, Krebs-Ringer bicarbonate; TC, total cholesterol; TG, triglycerides; TNF
, tumor necrosis factor alpha
Supplementary key words atlas human cDNA expression array TNF
IL-6 cell cycle genes
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