Journal
DIABETOLOGIA
Volume 51, Issue 11, Pages 2060-2067Publisher
SPRINGER
DOI: 10.1007/s00125-008-1132-7
Keywords
CCL5; gene expression; inflammation; insulin resistance; insulin sensitivity; metabolic syndrome; peripheral blood mononuclear cells; TLR; TNF; weight reduction
Categories
Funding
- Sigrid Juselius Foundation, the Academy of Finland [209445, 211497]
- State subsidy funding system (EVO) [5179, 5198]
- Ministry of Education in Finland [125/722/2003]
- Yrjo Johansson Foundation,
- Finnish Foundation
- City of Kuopio
- Conselho Nacional de Desenvolvimento Cient fico e Tecnologico (National Council of Scientific and Technological Development), Brazil
- Austrian Academy of Sciences
- Academy of Finland (AKA) [209445, 209445] Funding Source: Academy of Finland (AKA)
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Aims/hypothesis The transcription factor nuclear factor-kappa-B (NF kappa B) 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 NF kappa B 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/interpretation 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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