Linking single brain gene variation to obesity

 Linking single brain gene variation to obesity

A single variation in the gene for brain-derived neurotropic factor (BDNF) may influence obesity in children and adults, according to a new study published in Cell Reports. The study suggests that a less common version of the BDNF gene may predispose people to obesity by producing lower levels of BDNF protein, a regulator of appetite, in the brain. 

“The BDNF gene has previously been linked to obesity, and scientists have been working for several years to understand how changes in this particular gene may predispose people to obesity,” said the author.

They first analyzed the BDNF gene for naturally occurring genetic changes that alter levels of BDNF production. After analyzing brain tissue samples, the researchers identified an area of the gene where a single change reduced BDNF levels in the hypothalamus, a key area that controls eating and body weight.

The genetic change the researchers identified was not a rare mutation, but rather a variation that occurs in the general population. Every person has two copies, or alleles, of each gene, inheriting one copy from each parent. Alleles can vary at any location across the gene. In their study, the researchers referred to the common allele as “T,” and the less common allele, which produces less BDNF protein, as “C.”

They compared a person’s BDNF gene combination—CC, CT or TT—to factors that define obesity, such as body mass index (BMI) and percentage of body fat. In African American adults, the team found that the C allele was associated with higher BMI and body fat percentage in those with CT or CC types. In a group of healthy children of many races, the researchers found that CC types had higher BMI scores and percentage of body fat when compared to CT or TT types, who were similar to each other. Finally, in a group of Hispanic children, the researchers found that the C allele (CT, CC types) was associated with a higher BMI score. Overall, the study suggests that the C allele of the BDNF gene may be linked to obesity in people.

To understand why the C allele has an effect on obesity, the study team carefully examined the genetic area that differs between C and T alleles. They discovered that the area of interest interacts with a protein called hnRNP D0B. In laboratory experiments, the team found that hnRNP D0B had trouble interacting with the C allele, resulting in less BDNF production. “Lower BDNF levels may contribute to obesity in people with the C allele. If these findings are supported by additional studies, boosting BDNF levels may prove beneficial,” said the author.