Defective chromosome cause of severe obesity

CNRSFeb 4 2010

A new cause of obesity due to a defect on chromosome 16 has just been discovered. It is thought to explain close to 1% of obesity cases. For carriers of the defect, the risk of becoming overweight is 50 times higher. This research is the result of close cooperation between the team of Professor Froguel, a CNRS researcher, in Lille, and colleagues at Imperial College in London and Vaudois University Hospital in Lausanne, with the support of ten other European research groups. The findings of the study are to be published in Nature on February 4, 2010.

Obesity is becoming increasingly prevalent worldwide, and its causes are linked to a number of factors. Several genes, about which our knowledge is constantly expanding, are implicated, as well as environmental factors. Although the rise in the number of overweight people is associated with clearly identified social causes (lack of exercise, diet, etc.), heredity also plays a major role in determining weight and the occurrence of obesity. Recent studies revealed the involvement of about thirty genes related to a weak or moderate increase in the risk of obesity (only 10 to 50% increase per gene).

With the support of colleagues throughout Europe, a Franco-British-Swiss team focused on the role played by the absence of a small fragment of chromosome 16 in the occurrence of a severe form of obesity. Identified with DNA microarrays, this genetic defect, which is more specifically known as "microdeletion" (loss of a tiny part of a chromosome), results in the suppression of thirty different genes in this region. Researchers discovered that this microdeletion is relatively common in obese people but lacking in the majority of the population. It was identified in 31 adolescents and adults who experienced learning difficulties at school. All carriers of the defect were obese. The scientists concluded that the defect undoubtedly played a role in weight regulation.

To determine whether this microdeletion is involved in common obesity, the scientists studied the DNA of 16,000 European individuals of different weights. Among them, 19 were carriers of the chromosome 16 microdeletion. These 19 individuals all became overweight during their childhood and adolescence, and subsequently became obese as adults.

The researchers thus discovered that this defect, which generally concerns less than one in 1000 people, explains close to 1% of cases of common obesity (and 3% of cases for overweight people who also suffer from mental development disorders). In addition, the risk of carriers of a chromosome 16 deletion developing severe obesity is increased 50-fold (risk increase of 5000%).

Although the identity of the gene(s) responsible for obesity remains to be established, it is probable that these genes play a role in the development of the brain. This chromosome region is effectively known to be linked to the development of schizophrenia and autism, both diseases often complicated by obesity. These findings also confirm the link between obesity and neuropsychiatric diseases. In identifying common causes for these diseases, the scientists conclude that obesity may be a neurobehavioral disease.

This work opens up prospects for the development of new targeted preventive treatments, based on the identification of genetic causes of obesity, and even of other common diseases, such as diabetes and hypertension.