Mutations In Gene Related To Obesity

Researchers from Imperial College London have discovered mutations is a gene related to obesity that may help lead to possibilities of new treatments in the global fight against the obesity epidemic as published in Nature Genetics.

Investigation into the genetic causes of obesity and obesity related conditions could be valuable in finding ways to treat them. Currently there are some drugs available and others are being tested to help combat obesity, but knowing what specific mutations cause obesity will allow scientists to create more effective drugs to target them specifically.

This study focussed on obese children in Pakistan. The genetic links to obesity had already been previously identified in 30% of the cases. The link of genes to obesity is caused by recessive mutations that are passed onto offspring in a region like Pakistan because of the high level of consanguinity in the population. Parents that are closely related are most likely to be carrying the same gene mutation, making it so that the offspring may inherit the mutated gene from both sides causing the mutation to take effect.

Genome sequencing discovered mutations in 1 specific gene called adenylate cyclase 3 which is related to obesity. When mutations occur in adenylate cyclase 3 the protein that it codes for forms abnormally making it so that it does not function properly, which leads to abnormalities relating to sense of smell, diabetes, and appetite control.

Mice model bred to lack adenylate cyclase 3 were found to be obese and lack the ability to smell, which is called anosmia. When the human patients were tested the also were found to have anosmia, showing a link to mutations in adenylate cyclase 3. Adenylate cyclase 3, ADCY3, is believed to impact a system which links the hypothalamus to the production of hormones that regulate a variety of biological functions which includes appetite.

After the mutations were identified in Pakistan and the results were entered into GeneMatcher it led to another group of scientist in the Netherlands contacting the team with their own findings regarding adenylate cyclase 3 in one of their patients with obesity. The European patient had inherited different mutations on the same adenylate cyclase 3 gene from both parents, making the adenylate cyclase 3 gene in the offspring not function properly leading to obesity. The parents were not closely related, as in Pakistan.

Additional connections were made with Danish scientists who were investigating the Inuit population of Greenland where consanguineous relationships are not traditional, but the population is small making it that inbreeding may have occurred.

Professor Froguel notes how positive collaboration is particularly in terms of showing that findings and research can be reproduced. Going on to add that obesity is not always gluttony, attempts to understand obesity and look for a cure are a strength of the Imperial Faculty and Department of Medicine.