title: Downregulation of genes involved in NFkappaB activation in peripheral blood mononuclear cells after weight loss is associated with the improvement of insulin sensitivity in individuals with the metabolic syndrome: the GENOBIN study.
abstract: OBJECTIVE
  The transcription factor nuclear factor-kappa-B (NFkappaB) is implicated in inflammatory responses, obesity and the metabolic syndrome, while immune cells appear to play a central role in mediating insulin resistance and can be used as a model to study inflammation and its relationship with insulin resistance. In peripheral blood mononuclear cells of overweight participants with the metabolic syndrome, we evaluated (1) the effect of diet-induced weight loss on the expression of genes involved in NFkappaB activation and (2) their association with insulin sensitivity. The genes studied were: TNF receptors TNFRSF1A and TNFRSF1B, and IL1R1, TLR4, TLR2, ICAM1, CCL5 and IKBKB.
  
  
  METHODS
  We analysed data from 34 overweight participants with abnormal glucose metabolism and the metabolic syndrome, who were randomised to a weight-reduction (n = 24) or control group (n = 10) for 33 weeks. The mRNA expression was measured using real-time PCR. Measures of insulin and glucose homeostasis were assessed by IVGTT and OGTT.
  
  
  RESULTS
  In general, the genes studied were downregulated after weight loss intervention. The changes in TLR4, TLR2, CCL5 and TNFRSF1A mRNA expression were associated with an increase in insulin sensitivity index independently of the change in waist circumference (p < 0.05). The change in IKBKB expression correlated with most of the changes in gene expression in the weight-reduction group.
  
  
  CONCLUSIONS
  These results suggest that proteins encoded by CCL5, TLR2 and TLR4, and TNFRSF1A might contribute to insulin-resistant states that characterise obesity and the metabolic syndrome.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT 00621205.
authors.affiliation: Department of Clinical Nutrition, Food and Health Research Centre, University of Kuopio, Kuopio 70211, Finland.
authors.forename: V D F
authors.initials: VD
authors.lastname: de Mello
authors.forename: M
authors.initials: M
authors.lastname: Kolehmainen
authors.forename: L
authors.initials: L
authors.lastname: Pulkkinen
authors.forename: U
authors.initials: U
authors.lastname: Schwab
authors.forename: U
authors.initials: U
authors.lastname: Mager
authors.forename: D E
authors.initials: DE
authors.lastname: Laaksonen
authors.forename: L
authors.initials: L
authors.lastname: Niskanen
authors.forename: H
authors.initials: H
authors.lastname: Gylling
authors.forename: M
authors.initials: M
authors.lastname: Atalay
authors.forename: R
authors.initials: R
authors.lastname: Rauramaa
authors.forename: M
authors.initials: M
authors.lastname: Uusitupa