Gene Expression in Obesity and Insulin Resistance

NCT00621205 | Completed

• 2 other identifiers: 152/2002Finnish Academy 210449
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 1

Brief Summary

Lifestyle and genetic factors interact in the development of obesity and the metabolic syndrome. The molecular mechanisms underlying the beneficial dietary modifications are, however, unclear. We aimed to examine the effect of the long-term 30 moderate weight reduction on gene expression in adipose tissue (AT) and to identify genes and gene clusters responsive to treatment and thereby likely contributing to the development of the metabolic syndrome. Thus, randomized controlled and individualized weight reduction and physical exercise intervention was conducted. In the WR group, glucose metabolism improved that was not seen in other groups. Moreover, an inverse correlation between the change in SI and the change in body weight was found (r =-0.44, p=0.026). Down-regulation of gene expression (p\<0.01) involving gene ontology groups of extracellular matrix, cell death was seen. Such changes did not occur in the other groups.

Conditions

Insulin Resistance; Metabolic Syndrome

Keywords

Insulin resistance, weight reduction, adipose tissue, peripheral; mononuclear cells, gene expression profile, transcriptomics

Interventions

Weight reduction, Resistance training, Aerobic exercise training, Control BEHAVIORAL

Weight reduction: 12 weeks intensive weight loss, 20 weeks maintenance Resistance and aerobic exercise training: individualized and progressive training programs

Eligibility Criteria

• Age: 40 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The subjects had impaired fasting glycemia (fasting plasma glucose concentration 5.6-7.0 mmol/L) or impaired glucose tolerance (2-hour plasma glucose concentration 7.8-11.0 mmol/L)
• AND at least 2 other features of the metabolic syndrome according to the Adult Treatment Panel III criteria as modified by the AHA:
• waist circumference \>102 cm (males)/ \>88 cm (females)
• fasting serum triacylglycerol concentration \>1.7 mmol/L
• fasting serum HDL-cholesterol \<1.0 mmol/L (males) / \<1.3 mmol/L (females)
• blood pressure \>130/80 mmHg.

You may not qualify if:

• liver, kidney and thyroid dysfunction

Sponsors & Collaborators

• Marjukka Kolehmainen: lead
• University of Eastern Finland: collaborator
• Wageningen University: collaborator

Study Sites (1)

University of Kuopio, School of Public Health and Clinical Nutrition, Department of Clinical Nutrition and Food and Health Research Centre

Kuopio, FI-70211, Finland

Location

Related Publications (5)

• Kolehmainen M, Salopuro T, Schwab US, Kekalainen J, Kallio P, Laaksonen DE, Pulkkinen L, Lindi VI, Sivenius K, Mager U, Siitonen N, Niskanen L, Gylling H, Rauramaa R, Uusitupa M. Weight reduction modulates expression of genes involved in extracellular matrix and cell death: the GENOBIN study. Int J Obes (Lond). 2008 Feb;32(2):292-303. doi: 10.1038/sj.ijo.0803718. Epub 2007 Sep 11.

  PMID: 17848939 RESULT

• de Mello VD, Kolehmainen M, Schwab U, Mager U, Laaksonen DE, Pulkkinen L, Niskanen L, Gylling H, Atalay M, Rauramaa R, Uusitupa M. Effect of weight loss on cytokine messenger RNA expression in peripheral blood mononuclear cells of obese subjects with the metabolic syndrome. Metabolism. 2008 Feb;57(2):192-9. doi: 10.1016/j.metabol.2007.08.024.

  PMID: 18191048 RESULT

• Hallikainen M, Kolehmainen M, Schwab U, Laaksonen DE, Niskanen L, Rauramaa R, Pihlajamaki J, Uusitupa M, Miettinen TA, Gylling H. Serum adipokines are associated with cholesterol metabolism in the metabolic syndrome. Clin Chim Acta. 2007 Aug;383(1-2):126-32. doi: 10.1016/j.cca.2007.05.006. Epub 2007 May 18.

  PMID: 17573060 RESULT

• de Mello VD, Kolehmainen M, Pulkkinen L, Schwab U, Mager U, Laaksonen DE, Niskanen L, Gylling H, Atalay M, Rauramaa R, Uusitupa M. 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. Diabetologia. 2008 Nov;51(11):2060-7. doi: 10.1007/s00125-008-1132-7. Epub 2008 Aug 30.

  PMID: 18758745 DERIVED

• Schwab U, Seppanen-Laakso T, Yetukuri L, Agren J, Kolehmainen M, Laaksonen DE, Ruskeepaa AL, Gylling H, Uusitupa M, Oresic M; GENOBIN Study Group. Triacylglycerol fatty acid composition in diet-induced weight loss in subjects with abnormal glucose metabolism--the GENOBIN study. PLoS One. 2008 Jul 9;3(7):e2630. doi: 10.1371/journal.pone.0002630.

  PMID: 18612464 DERIVED

MeSH Terms

Conditions

Insulin Resistance; Metabolic Syndrome; Weight Loss

Interventions

Resistance Training

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Body Weight Changes; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Exercise Therapy; Rehabilitation; Aftercare; Continuity of Patient Care; Patient Care; Therapeutics; Physical Therapy Modalities; Physical Conditioning, Human; Exercise; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Officials

• Helena Gylling, Professor

  Unievrsity of Kuopio

  PRINCIPAL INVESTIGATOR

• Matti IJ Uusitupa, Professor

  University of Eastern Finland

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Senior scientist

Study Record Dates

• First Submitted: February 11, 2008
• First Posted: February 22, 2008
• Study Start: October 1, 2003
• Primary Completion: December 1, 2004
• Study Completion: December 1, 2005
• Last Updated: April 17, 2012

Record last verified: 2012-04

Locations

FI (1)