Genetics and the pathophysiology of obesity.

Obesity is a complex disease that involves interactions between environmental and genetic factors. Obesity results from an imbalance between food intake and energy expenditure over several years. The genetic approach both in animal models and in humans has allowed immense progress in the understanding of body weight regulation. Monogenic forms of obesity in humans have been characterized and result from mutations in genes involved in the central pathways of food intake regulation. However, these cases are extremely rare and generally obesity must be considered as a complex polygenic disease involving interactions between multiple genes and the environment. Numerous studies, including studies in children, have tried to identify "susceptibility" genes. At present, the results are not conclusive inasmuch as they are highly variable between studies and because the relative risk associating a specific gene allele and obesity remains low. Thus, it seems highly premature to genotype obese patients on a large scale for predictive testing. When specific pharmacological treatments based on recent discoveries become available, however, genetic testing could help discriminate between the subtypes of obesity that may respond differentially to treatment.