Journal Article

Weight reduction modulates expression of genes involved in extracellular matrix and cell death: the GENOBIN study

Pulkkinen, L, Kallio, P, Salopuro, T, Kolehmainen, M, Kekalainen, J, Mager, U, Schwab, U.S, Sivenius, K, Laaksonen, D.E, Lindi, V.I

2008

Overview

Objective: 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 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. Design: Randomized controlled and individualized weight reduction intervention. Subjects: Forty-six subjects with impaired fasting glycemia or impaired glucose tolerance and features of metabolic syndrome, aged 60±7 years were randomized either to a weight reduction (WR) ( n =28) or a control ( n =18) group lasting for 33 weeks. Measurements: Oral and intravenous glucose tolerance tests and subcutaneous AT biopsies were performed before and after the intervention. Gene expression of AT was studied using microarray technology in subgroups of WR (with weight reduction ⩾5%, n =9) and control group ( n =10). The results were confirmed using quantitative PCR. Results: In the WR group, glucose metabolism improved. Moreover, an inverse correlation between the change in S I and the change in body weight was found ( r =−0.44, P =0.026). Downregulation of gene expression ( P <0.01) involving gene ontology groups of extracellular matrix and cell death was seen. Such changes did not occur in the control group. The tenomodulin-gene was one of the most downregulated genes (−39±16%, P <0.0001). Moreover, its expression correlated with insulin sensitivity ( r =−0.34, P =0.005) before the intervention and with body adiposity both before ( r =0.42, P =0.007) and after ( r =0.30, P =0.056) the intervention. Conclusion: Genes regulating the extracellular matrix and cell death showed a strong downregulation after long-term weight reduction. This likely reflects a new stable state at the molecular level in AT. Further studies are warranted to elucidate the mechanisms of these genetic factors.

• Publisher: Nature Publishing Group UK,Nature Publishing,Nature Publishing Group
• Subject: Adipose tissue / Adult / Aged / Biological and medical sciences / blood glucose / Blood Glucose - metabolism / Body weight / Case-Control Studies / Cell death / Cell Death - genetics / diet therapy / Epidemiology / extracellular matrix / Extracellular Matrix - genetics / Female / Gene expression / Gene Expression Regulation / genes / Genetic aspects / Genetic factors / genetics / GENOBIN study / Glucose / glucose tolerance / Glucose Tolerance Test / Health Promotion and Disease Prevention / Humans / Insulin / Insulin - metabolism / Internal Medicine / Intervention / lifestyle / Male / Medical sciences / Medicine / Medicine & Public Health / men / Metabolic Diseases / Metabolic disorders / metabolic syndrome / Metabolic Syndrome - genetics / Metabolic syndrome X / metabolism / Methods / Middle Aged / Mortality / nutritional intervention / Obesity / Obesity - diet therapy / Obesity - genetics / original-article / Public Health / Risk factors / Weight loss / Weight Loss - genetics / women