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Obesity — a genetic disease of adipose tissue?

Published online by Cambridge University Press:  09 March 2007

Peter Arner
Peter Arner*
Affiliation:
Karolinska Institute, Department of Medicine, CME, M61, Huddinge Hospital, S-141 86 Huddinge, Stockholm, Sweden
*
*Corresponding author: P. Arner, fax +46 8 58582407, email peter.arner@medhs.ki.se
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Abstract

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Although the rapid increase in the prevalence of obesity in many countries suggests that environmental factors (mainly overeating and physical inactivity) play the most important role in the development of overweight, it is very likely that genetic factors also contribute. It appears that one major gene in combination with one or several minor genes constitute the genetic components behind excess accumulation of body fat in most obese individuals. However, monogenic obesity has been described in a few families due to changes in leptin, leptin receptor, prohormone convertase, pro-opiomelanocortin or melanocortin-4 receptor. None of the monogenic variants is of great importance for common human obesity; the latter genes are unknown so far. Results from genomic scans suggest that major obesity genes are located on chromosomes 2, 10, 11 and 20. Studies of candidate genes indicate that the minor obesity genes control important functions of adipose tissue, and that structural variance in these genes may alter adipose tissue function in a way that promotes obesity. Such genes are β2- and β3-adrenoceptors, hormone-sensitive lipase, tumour necrosis factor alpha, uncoupling protein-1, low-density lipoprotein receptor, and peroxisome proliferator activator receptor gamma-2. Some of these genes may promote obesity by gene–gene interactions (for example β3-adrenoceptors and uncoupling protein-1) or gene–environment interactions (for example β2-adrenoceptors and physical activity). Some are important for obesity only among women (for example β2- and β3-adrenoceptors, low-density lipoprotein receptor and tumour necrosis factor alpha). Few ‘non-adipose’ genes have so far shown a firm association to common human obesity, which could suggest that the important genes for the development of excess body fat also control adipose tissue function.

Keywords

Fat cellsBody mass indexLipolysisThermogenesisAdipocyte differentiation
Type
Research Article
Information
British Journal of Nutrition , Volume 83 , Issue S1 , June 2000 , pp. S9 - S16
Copyright
Copyright © The Nutrition Society 2000

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