Gene Expression in Obesity and Insulin Resistance

Metabolic Syndrome Clinical Trial

— Genobin  

Official title:

Gene Expression in Adipose Tissue of Genes Involved in Obesity, Insulin Resistance and Lipid Metabolism Before and After Weight Loss or an Intensive Exercise Period

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00621205
• Other study ID #: 152/2002
• Secondary ID: Finnish Academy
• Status: Completed
• Phase: N/A
• First received: February 11, 2008
• Last updated: April 16, 2012
• Start date: October 2003
• Est. completion date: December 2005

Study information

• Verified date: April 2012
• Source: University of Eastern Finland
• Contact: n/a
• Is FDA regulated: No
• Health authority: Finland: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

Description:

The objective of the study is to examine the expression of genes and gene regions involved in obesity, insulin resistance and lipid metabolism. We aim to identify new genes which are involved in the development of metabolic aberrations characteristic of metabolic syndrome/type 2 diabetes. Obesity and type 2 diabetes are increasing medical and public health problems globally. Low HDL cholesterol and elevated triglyceride concentrations, and altered cholesterol metabolism are common in these states. More knowledge is urgently needed of the role of genetics in obesity, insulin resistance and abnormal lipid metabolism and their mutual relationship. This would enable the early detection of subjects at increased risk of developing obesity and the common abnormalities related to it, i.e. insulin resistance and abnormal lipid metabolism, as well as identification of subjects with genotypes associated with increased risk for above mentioned metabolic states and atherosclerotic vascular diseases and decreased responsiveness to conventional treatment. Because both weight loss and regular physical exercise result in substantial changes in glucose, insulin and lipid metabolism, studies aiming to explore the function of relevant genes are highly interesting. In this study, gene expression will be measured in adipose tissue and leucocytes before and after weight loss or period of regular physical exercise.

Originally, the Genobin study included 75 middle-aged (mean age 60±7 years) overweight or obese (mean BMI 32.9±2.8 kg/m2) men and women with impaired fasting glucose (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 fasting plasma glucose <7.1 mmol/l) and two additional features of metabolic syndrome according to the Adult Treatment Panel III criteria [49] (for details see [50]). Subjects were randomized to one of the following groups: weight reduction (WR) (n=28), aerobic exercise training (n=15), resistance exercise training (n=14) or control group (n=18). Subjects were matched for age, sex and the status of glucose metabolism. In addition, 11 normal-weight subjects (mean age 48±9 years, mean BMI 23.7±1.9 kg/m2) were recruited. The intervention was performed in accordance with the standards of the Helsinki Declaration. The Ethics Committee of the District Hospital Region of Northern Savo and Kuopio University Hospital approved the study plan, and all participants gave written informed consent.

At the beginning of the study and after 9-11 months the following measurements were performed: plasma/serum concentrations of glucose, insulin, total and lipoprotein lipids, free fatty acids, non-cholesterol sterols, glycerol, leptin, adiponectin, ghrelin, tumor necrosis factor α, and C-reactive protein, waist and hip circumferences, body composition and resting energy expenditure. A DNA sample were drawn and an adipose tissue biopsy was performed. A frequently sampled intravenous glucose tolerance test (FSIGT) was performed to assess insulin sensitivity and secretion. Given biochemical measurements were performed also at 3 months.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 75
• Est. completion date: December 2005
• Est. primary completion date: December 2004
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 40 Years to 70 Years

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• liver, kidney and thyroid dysfunction

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Insulin Resistance
• Metabolic Syndrome
• Metabolic Syndrome X

Intervention

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

Locations

Country	Name	City	State
Finland	University of Kuopio, School of Public Health and Clinical Nutrition, Department of Clinical Nutrition and Food and Health Research Centre	Kuopio

Sponsors (3)

Lead Sponsor	Collaborator
Marjukka Kolehmainen	University of Eastern Finland, Wageningen University

Country where clinical trial is conducted

Finland, 

References & Publications (3)

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 — View Citation

Hallikainen M, Kolehmainen M, Schwab U, Laaksonen DE, Niskanen L, Rauramaa R, Pihlajamäki 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- — View Citation

Kolehmainen M, Salopuro T, Schwab US, Kekäläinen 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 mat — View Citation