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Downregulation of genes involved in NFκB 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

Aims/hypothesis The transcription factor nuclear factor-kappa-B (NFκB) 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 w... Full description

Journal Title: Diabetologia 2008-08-30, Vol.51 (11), p.2060-2067
Main Author: de Mello, V. D. F
Other Authors: Kolehmainen, M , Pulkkinen, L , Schwab, U , Mager, U , Laaksonen, D. E , Niskanen, L , Gylling, H , Atalay, M , Rauramaa, R , Uusitupa, M
Format: Electronic Article Electronic Article
Language: English
Subjects:
TLR
TNF
Publisher: Berlin/Heidelberg: Springer-Verlag
ID: ISSN: 0012-186X
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recordid: cdi_springer_primary_2008_125_51_11_1132
title: Downregulation of genes involved in NFκB 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
format: Article
creator:
  • de Mello, V. D. F
  • Kolehmainen, M
  • Pulkkinen, L
  • Schwab, U
  • Mager, U
  • Laaksonen, D. E
  • Niskanen, L
  • Gylling, H
  • Atalay, M
  • Rauramaa, R
  • Uusitupa, M
subjects:
  • Article
  • CCL5
  • Gene expression
  • Human Physiology
  • Inflammation
  • Insulin resistance
  • Insulin sensitivity
  • Internal Medicine
  • Medicine
  • Medicine & Public Health
  • Metabolic Diseases
  • Metabolic syndrome
  • Peripheral blood mononuclear cells
  • TLR
  • TNF
  • Weight reduction
ispartof: Diabetologia, 2008-08-30, Vol.51 (11), p.2060-2067
description: Aims/hypothesis The transcription factor nuclear factor-kappa-B (NFκB) 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 NFκB 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  
language: eng
source:
identifier: ISSN: 0012-186X
fulltext: no_fulltext
issn:
  • 0012-186X
  • 1432-0428
url: Link


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titleDownregulation of genes involved in NFκB 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
creatorde Mello, V. D. F ; Kolehmainen, M ; Pulkkinen, L ; Schwab, U ; Mager, U ; Laaksonen, D. E ; Niskanen, L ; Gylling, H ; Atalay, M ; Rauramaa, R ; Uusitupa, M
creatorcontribde Mello, V. D. F ; Kolehmainen, M ; Pulkkinen, L ; Schwab, U ; Mager, U ; Laaksonen, D. E ; Niskanen, L ; Gylling, H ; Atalay, M ; Rauramaa, R ; Uusitupa, M
descriptionAims/hypothesis The transcription factor nuclear factor-kappa-B (NFκB) 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 NFκB 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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subjectArticle ; CCL5 ; Gene expression ; Human Physiology ; Inflammation ; Insulin resistance ; Insulin sensitivity ; Internal Medicine ; Medicine ; Medicine & Public Health ; Metabolic Diseases ; Metabolic syndrome ; Peripheral blood mononuclear cells ; TLR ; TNF ; Weight reduction
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atitleDownregulation of genes involved in NFκB 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
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date2008-08-30
risdate2008
volume51
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pages2060-2067
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abstractAims/hypothesis The transcription factor nuclear factor-kappa-B (NFκB) 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 NFκB 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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pubSpringer-Verlag
doi10.1007/s00125-008-1132-7
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