Genetics of food intake, weight and obesity
For decades, body weight maintenance has been under genetic control, mainly due to the identification of mouse mutations that cause obesity. Recently, under great excitement, several such genes have been cloned from mice and humans, and it is likely that additional genetic determinants will be identified soon.
Understanding the motivation for genetic control of excess weight can be largely attributed to two factors:
Obesity is a huge problem in developed countries, and the appeal of drugs to solve this problem is powerful.
The development of obesity in adulthood is closely related to the development of other important diseases (including diabetes, hypertension, and heart disease).
Preliminary identification of “obesity genes”
To understand the physiology behind the “obesity gene” currently being investigated, it is valuable to first review some experiments conducted in the 1960s using antipodal mice. An antibiotic treatment technique rarely used today involves making incisions along the sides of two animals and then suture them together to form a symmetrical pair. The key use of this technology is to combine the vascular systems of two animals to exchange blood-borne molecules.
Many years ago, geneticists identified two recessive mutations in mice. If they are homozygous, the mice will become severely obese. The two genes are called ob and db. The Parabiotic pair constructed between ob/ob, db/db and normal mice led to the following observations:
Pair obese ob/ob mice with normal mice: ob/ob mice lose weight
Pair obese db/db mice with normal mice: Normal mice stop eating and lose weight
Pair the obese ob/ob mouse with the obese db/db mouse: the ob/ob mouse stops eating and loses weight, while the db/db mouse is not affected.
Another experiment showed that when one of a pair of normal aligned mice was exceeded, its “double” weight lost.