Biomedicine

The Genetics of Overeating

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Science  04 Apr 2003:
Vol. 300, Issue 5616, pp. 21
DOI: 10.1126/science.300.5616.21b

While it is generally accepted that genetics plays a role in obesity, the culprit genes have been difficult to identify because this disorder typically arises from the combined effects of multiple genes and environmental factors. The MC4R gene, which encodes the melanocortin 4 receptor, is one of the few genes causally linked to rare, monogenic forms of obesity. New work reinforces the idea that MC4R mutations are strong contributors to the development of morbid obesity induced by hyperphagia (overeating) and suggests that these mutations may be more common than previously thought.

In a study of 500 patients with severe childhood obesity, Farooqi et al. found that nearly 6% had mutations in MC4R and that the severity of their clinical phenotype correlated with impairment of receptor function. Independently, Branson et al. found that sequence changes in MC4R were especially prevalent in obese subjects who engaged in binge eating, although the functional effects of the sequence changes were not tested. Recent mouse data from Weide et al. support the hypothesis that hyperphagia, rather than reduced metabolism, is the primary disturbance leading to early-onset obesity in the MC4R-deficient state.—PAK

N. Engl. J. Med.348, 1085; 1096 (2003); Physiol. Genomics13, 47 (2003).

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