Hunting for human obesity genes? Look in the adipose tissue!

Abstract

Over-eating and physical inactivity in combination with genetic factors play the most important roles in the development of over weight in humans. The common genetic components behind excess accumulation of body fat are so far unknown. Studies of candidate genes indicate that most of the genes that associate with obesity control important functions of adipose tissue as well. Furthermore, structural variations in these genes may alter adipose tissue function in a way that promotes obesity. The genes which both are functional in human adipose tissue and associate with obesity are: hormone sensitive lipase, β₂ and β₃-adrenoceptors, tumor necrosis factor α, low density lipoprotein receptor, uncoupling protein-1 and peroxisome proliferator activated receptor γ-2. Other genes are mostly important for obesity among women (for example β₂ -and β₃-adrenoceptors, low density lipoprotein receptor and tumor necrosis factor α). Some of these genes may promote obesity by gene–gene interactions (for example β₃-adrenoceptors and uncoupling protein-1) or gene–environmental interactions (for example β₂-adrenoceptors and physical activity). Few genes with no known function in adipose tissue have shown a firm association with excess body fat. The latter suggests that the important human obesity genes also control adipose tissue function. Therefore it might be of value to focus the further hunt for obesity genes on the fat tissue.