Article

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.

Department of Clinical Nutrition, Food and Health Research Centre, University of Kuopio, Kuopio 70211, Finland.
Diabetologia (impact factor: 6.81). 09/2008; 51(11):2060-7. DOI:10.1007/s00125-008-1132-7 pp.2060-7
Source: PubMed

ABSTRACT 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.
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.
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.
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. Trial registration: ClinicalTrials.gov NCT 00621205.

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    PLoS ONE 01/2010; 5(11):e13980. · 4.09 Impact Factor
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Keywords

34 overweight participants
 
abnormal glucose metabolism
 
central role
 
diet-induced weight loss
 
gene expression
 
IKBKB expression correlated
 
immune cells
 
insulin resistance
 
insulin sensitivity
 
insulin sensitivity index
 
insulin-resistant states
 
mediating insulin resistance
 
metabolic syndrome
 
mRNA expression
 
peripheral blood mononuclear cells
 
real-time PCR
 
study inflammation
 
TNFRSF1A mRNA expression
 
Trial registration
 
weight loss intervention