What causes obesity? This question continues to puzzle scientists and those living with the condition.

An increasing amount of studies are helping to remove the social stigma surrounding obesity, pointing to appetite-controlling hormones or even brain cells as potential causes.

Some are also pointing to genetic mutations as potential culprits for the condition. For example, Medical News Today have recently reported on a study in which mice gained weight without eating more as a result of having a certain gene variant. This made the researchers refer to the phenomenon as “fault-free obesity.”

Another previous study — led by Prof. Philippe Froguel, who is chair of genomic medicine at Imperial College London (ICL) in the United Kingdom — found that variants in three genes accounted for 30 percent of the severe obesity cases identified in a Pakistani population.

The same team of ICL researchers have now chosen to focus on a group of Pakistani children with extreme obesity from consanguineous families, or those that descend from the same ancestor, in an attempt to single out a specific gene mutation.

As the authors of the new study explain, so-called recessive mutations are responsible for the link between obesity and genes. Recessive inheritance occurs when both copies of the gene — that is, from both parents — have the mutation, and this is more likely to occur when a child’s parents are closely related.

So, Prof. Froguel and colleagues used genome sequencing in Pakistani children because people in this region are more likely to form consanguineous marriages, and the resulting children are more likely to have recessive mutations.

The new study — which was recently published in the journal Nature Genetics — suggests that mutations in a gene called adenylate cyclase 3 (ADCY3) lead to obesity.

ADCY3 gene mutation may cause obesity

According to the authors, mutations in this gene — which is normally responsible for encoding the protein of the same name — causes changes in functions such as appetite regulation and the olfactory sense.

As Prof. Froguel explains, “Early studies into ADCY3 tested mice that were bred to lack that gene, found that these animals were obese and also lacked the ability to smell, known as anosmia.”

Additionally, using the GeneMatcher website, Prof. Froguel and colleagues found another patient — this time of European-American descent — who had inherited different ADCY3 mutations from both parents and who also had obesity.

Findings may lead to new obesity treatments

Together, the study authors conclude, “These findings highlight ADCY3 as an important mediator of energy homeostasis and an attractive pharmacological target in the treatment of obesity.”

Knowing precisely which genetic mutations lead to obesity will enable researchers to come up with drugs that target these mutations specifically, the authors explain.