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Downregulation of genes involved in NFIoB 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

Byline: V. D. F. Mello (1,2), M. Kolehmainen (1), L. Pulkkinen (1), U. Schwab (1,3), U. Mager (1), D. E. Laaksonen (3), L. Niskanen (3), H. Gylling (1,3), M. Atalay (4), R. Rauramaa (5,6), M. Uusitupa (1) Keywords: CCL5; Gene expression; Inflammation; Insulin resistance; Insulin sensitivity; Metabol... Full description

Journal Title: Diabetologia 2008-11-01, Vol.51 (11), p.2060
Main Author: 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:
RNA
Publisher: Springer
ID: ISSN: 0012-186X
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title: Downregulation of genes involved in NFIoB 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:
  • 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:
  • Analysis
  • Anopheles
  • Cell research
  • Dextrose
  • Gene expression
  • Genes
  • Genetic aspects
  • Genetic research
  • Glucose
  • Glucose tolerance tests
  • Inflammation
  • Insulin
  • Insulin resistance
  • Medical research
  • Medicine, Experimental
  • Messenger RNA
  • Obesity
  • Physiological aspects
  • Proteins
  • RNA
  • Weight loss
ispartof: Diabetologia, 2008-11-01, Vol.51 (11), p.2060
description: Byline: V. D. F. Mello (1,2), M. Kolehmainen (1), L. Pulkkinen (1), U. Schwab (1,3), U. Mager (1), D. E. Laaksonen (3), L. Niskanen (3), H. Gylling (1,3), M. Atalay (4), R. Rauramaa (5,6), M. Uusitupa (1) Keywords: CCL5; Gene expression; Inflammation; Insulin resistance; Insulin sensitivity; Metabolic syndrome; Peripheral blood mononuclear cells; TLR; TNF; Weight reduction Aims/hypothesis The transcription factor nuclear factor-kappa-B (NFIoB) 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 NFIoB 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 NFIoB 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
creatorMello, V. D. F ; Kolehmainen, M ; Pulkkinen, L ; Schwab, U ; Mager, U ; Laaksonen, D. E ; Niskanen, L ; Gylling, H ; Atalay, M ; Rauramaa, R ; Uusitupa, M
creatorcontribMello, V. D. F ; Kolehmainen, M ; Pulkkinen, L ; Schwab, U ; Mager, U ; Laaksonen, D. E ; Niskanen, L ; Gylling, H ; Atalay, M ; Rauramaa, R ; Uusitupa, M
descriptionByline: V. D. F. Mello (1,2), M. Kolehmainen (1), L. Pulkkinen (1), U. Schwab (1,3), U. Mager (1), D. E. Laaksonen (3), L. Niskanen (3), H. Gylling (1,3), M. Atalay (4), R. Rauramaa (5,6), M. Uusitupa (1) Keywords: CCL5; Gene expression; Inflammation; Insulin resistance; Insulin sensitivity; Metabolic syndrome; Peripheral blood mononuclear cells; TLR; TNF; Weight reduction Aims/hypothesis The transcription factor nuclear factor-kappa-B (NFIoB) 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 NFIoB 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 Author Affiliation: (1) School of Public Health and Clinical Nutrition, Department of Clinical Nutrition, Food and Health Research Centre, University of Kuopio, P.O. Box 1627, Kuopio, 70211, Finland (2) Department of Internal Medicine, Federal University of Rio Grande do Sul, Porto Alegre, Brazil (3) Institute of Clinical Medicine, Internal Medicine, Kuopio University Hospital, Kuopio, Finland (4) Institute of Biomedicine, Physiology, University of Kuopio, Kuopio, Finland (5) Kuopio Research Institute of Exercise Medicine, University of Kuopio, Kuopio, Finland (6) Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, Kuopio, Finland Article History: Registration Date: 06/08/2008 Received Date: 21/05/2008 Accepted Date: 28/07/2008 Online Date: 30/08/2008
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subjectAnalysis ; Anopheles ; Cell research ; Dextrose ; Gene expression ; Genes ; Genetic aspects ; Genetic research ; Glucose ; Glucose tolerance tests ; Inflammation ; Insulin ; Insulin resistance ; Medical research ; Medicine, Experimental ; Messenger RNA ; Obesity ; Physiological aspects ; Proteins ; RNA ; Weight loss
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6Niskanen, L
7Gylling, H
8Atalay, M
9Rauramaa, R
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0Downregulation of genes involved in NFIoB 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
1Diabetologia
descriptionByline: V. D. F. Mello (1,2), M. Kolehmainen (1), L. Pulkkinen (1), U. Schwab (1,3), U. Mager (1), D. E. Laaksonen (3), L. Niskanen (3), H. Gylling (1,3), M. Atalay (4), R. Rauramaa (5,6), M. Uusitupa (1) Keywords: CCL5; Gene expression; Inflammation; Insulin resistance; Insulin sensitivity; Metabolic syndrome; Peripheral blood mononuclear cells; TLR; TNF; Weight reduction Aims/hypothesis The transcription factor nuclear factor-kappa-B (NFIoB) 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 NFIoB 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 Author Affiliation: (1) School of Public Health and Clinical Nutrition, Department of Clinical Nutrition, Food and Health Research Centre, University of Kuopio, P.O. Box 1627, Kuopio, 70211, Finland (2) Department of Internal Medicine, Federal University of Rio Grande do Sul, Porto Alegre, Brazil (3) Institute of Clinical Medicine, Internal Medicine, Kuopio University Hospital, Kuopio, Finland (4) Institute of Biomedicine, Physiology, University of Kuopio, Kuopio, Finland (5) Kuopio Research Institute of Exercise Medicine, University of Kuopio, Kuopio, Finland (6) Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, Kuopio, Finland Article History: Registration Date: 06/08/2008 Received Date: 21/05/2008 Accepted Date: 28/07/2008 Online Date: 30/08/2008
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titleDownregulation of genes involved in NFIoB 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
authorMello, V. D. F ; Kolehmainen, M ; Pulkkinen, L ; Schwab, U ; Mager, U ; Laaksonen, D. E ; Niskanen, L ; Gylling, H ; Atalay, M ; Rauramaa, R ; Uusitupa, M
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11Insulin
12Insulin resistance
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19RNA
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atitleDownregulation of genes involved in NFIoB 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
jtitleDiabetologia
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abstractByline: V. D. F. Mello (1,2), M. Kolehmainen (1), L. Pulkkinen (1), U. Schwab (1,3), U. Mager (1), D. E. Laaksonen (3), L. Niskanen (3), H. Gylling (1,3), M. Atalay (4), R. Rauramaa (5,6), M. Uusitupa (1) Keywords: CCL5; Gene expression; Inflammation; Insulin resistance; Insulin sensitivity; Metabolic syndrome; Peripheral blood mononuclear cells; TLR; TNF; Weight reduction Aims/hypothesis The transcription factor nuclear factor-kappa-B (NFIoB) 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 NFIoB 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 Author Affiliation: (1) School of Public Health and Clinical Nutrition, Department of Clinical Nutrition, Food and Health Research Centre, University of Kuopio, P.O. Box 1627, Kuopio, 70211, Finland (2) Department of Internal Medicine, Federal University of Rio Grande do Sul, Porto Alegre, Brazil (3) Institute of Clinical Medicine, Internal Medicine, Kuopio University Hospital, Kuopio, Finland (4) Institute of Biomedicine, Physiology, University of Kuopio, Kuopio, Finland (5) Kuopio Research Institute of Exercise Medicine, University of Kuopio, Kuopio, Finland (6) Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, Kuopio, Finland Article History: Registration Date: 06/08/2008 Received Date: 21/05/2008 Accepted Date: 28/07/2008 Online Date: 30/08/2008
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