title: Upregulation of skeletal muscle inflammatory genes links inflammation with insulin resistance in women with the metabolic syndrome.
abstract: The metabolic syndrome, a combination of interrelated metabolic risk factors, is associated with insulin resistance and promotes the development of cardiovascular diseases and type 2 diabetes mellitus. There is a close link between inflammation and metabolic disease, but the responsible mechanisms remain elusive. The aim of this study was to identify differentially expressed genes in insulin-resistant skeletal muscle tissue of women with the metabolic syndrome compared with healthy control women. Women with the metabolic syndrome (n = 19) and healthy control women (n = 20) were extensively phenotyped, insulin sensitivity was measured using a hyperinsulinaemic euglycaemic clamp, and a skeletal muscle biopsy was obtained. Gene expression levels were compared between the two groups by microarrays. The upregulated genes in skeletal muscle of the women with the metabolic syndrome were primarily enriched for inflammatory response-associated genes. The three most significantly upregulated of this group, interleukin 6 receptor (IL6R), histone deacetylase 9 (HDAC9) and CD97 molecule (CD97), were significantly correlated with insulin resistance. Taken together, these findings suggest an important role for a number of inflammatory-related genes in the development of skeletal muscle insulin resistance.
authors.affiliation: M. T. E. Hopman: Radboud University Nijmegen Medical Centre, Department of Physiology (392), PO Box 9101, 6500 HB Nijmegen, The Netherlands. m.hopman@fysiol.umcn.nl.
authors.forename: Fleur
authors.initials: F
authors.lastname: Poelkens
authors.forename: Gerwen
authors.initials: G
authors.lastname: Lammers
authors.forename: Elisabeth M
authors.initials: EM
authors.lastname: Pardoel
authors.forename: Cees J
authors.initials: CJ
authors.lastname: Tack
authors.forename: Maria T E
authors.initials: MT
authors.lastname: Hopman
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000235:genetics*; D005260:Female; D015309:Glucose Clamp Technique; D006655:Histone Deacetylases / Q000235:genetics*; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics* / Q000502:physiology; D024821:Metabolic Syndrome / Q000378:metabolism*; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism*; D040081:Protein Array Analysis; D043562:Receptors, G-Protein-Coupled; D019947:Receptors, Interleukin-6 / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*; D059467:Transcriptome; D015854:Up-Regulation
chemical_list: C095004:ADGRE5 protein, human; D015703:Antigens, CD; C508603:IL6R protein, human; D043562:Receptors, G-Protein-Coupled; D019947:Receptors, Interleukin-6; D012097:Repressor Proteins; C486544:HDAC9 protein, human; D006655:Histone Deacetylases