Obesity and polymorphisms in genes regulating human adipose tissue.

ABSTRACT

Obesity is the result of an imbalance between food intake and energy expenditure resulting in the storing of energy as fat. Adipose tissue contains the largest store of energy in the body and plays important roles in regulating energy partitioning. Developments in genomics, in particular microarray-based expression profiling, have provided scientists with a number of new candidate genes whose expression in adipose tissue is regulated by obesity. Integrating expression profiles with genome-wide linkage and/or association analyses is a promising strategy to identify new genes underlying susceptibility to obesity. This article provides a comprehensive review of adipose-tissue-expressed genes implicated in predisposition to human obesity. The authors consider the following genes of particular interest peroxisome proliferator-activated receptor gamma and, potentially, INSIG2 acting in adipogenesis; the adrenoreceptors beta 2 and 3, as well as hormone-sensitive lipase acting on lipolysis; uncoupling protein 2 acting in mitochondria energy expenditure; and among secreted molecules the cytokine tumor necrosis factor alpha and the hormone leptin. With the rapid development in genome research, we predict that additional alleles in genes regulating adipose tissue function will be established as risk factors for common obesity in the coming years. This has important implications for the prevention of obesity and may also offer new therapeutic targets.