Digestive System > Pregastric Physiology

Genetics of Food Intake, Body Weight and Obesity

It has been clear for several decades that maintenance of body weight is under genetic control, largely due to identification of mutations in mice that result in obesity. Recently, amid great excitement, several such genes have been cloned from mice and humans, and it's very likely that additional genetic determinants will soon be identified.

The incentive to understand genetic control over body weight can largely be attributed to two factors:

Initial Identification of "Obesity Genes"

To understand the physiology behind the "obesity genes" currently under investigation, it is valuable to first look back at some experiments conducted in the 1960's using parabiotic mice. The technique of parabiosis, which is rarely used today, involves making an incision along the lateral aspect of two animals, then suturing them together to form a parabiotic pair. The key utility of this technique is that it unites the vascular systems of the two animals, allowing exchange of blood-borne molecules.

Many years ago, geneticists identified in mice two recessive mutations which, if homozygous, led the mice to become grossly obese. The two genes were termed ob and db. Parabiotic pairs constructed between ob/ob, db/db and normal mice led to the following observations:

These observations were consistent with the idea that a satiety hormone, presumably the ob gene product, is produced which binds to receptors, presumably the db gene product, in the hypothalamus and suppresses hunger.

Considerable support was recently obtained for this model by the cloning of the ob and db genes from several species. The ob gene encodes the hormone leptin and the db gene the leptin receptor. Leptin is secreted by fat cells and has dual activity of decreasing food intake and increasing metabolic rate, which makes the old "lipostatic theory" for control of food intake very appealing.

Genes Involved in Maintaining Body Weight

It is clear that leptin and its receptor are only two of what may turn out to be a large number of genes that are important genetic determinants in the control of body weight and pathogenesis of obesity. Some of the other genes and gene products identified so far that are involved in control of food intake and body weight include:

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