Upregulation of skeletal muscle inflammatory genes links inflammation with insulin resistance in women with the metabolic syndrome

Abstract

New Findings: • What is the central question of this study? There is a close relationship between insulin resistance and inflammation, but it is largely unknown how these processes are linked in skeletal muscle tissue. • What is the main finding and its importance? Gene expression microarray analysis identified three inflammatory genes the expression level of which was highly correlated with insulin resistance in women with the metabolic syndrome. This suggests an important role for these genes in the development of skeletal muscle insulin resistance. 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. © 2013 The Authors. Experimental Physiology © 2013 The Physiological Society.