Researchers link single gene variation to obesity

NIH | NOVEMBER 1, 2015

A single variation in the gene for brain-derived neurotrophic factor (BDNF) may influence obesity in children and adults, according to a new study.

Variation in the BDNF gene may affect brain’s regulation of appetite. Image: NIH

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 authors propose that boosting BDNF protein levels may offer a therapeutic strategy for people with the genetic variation, which tends to occur more frequently in African Americans and Hispanics, than in non-Hispanic Caucasians.

Importantly, genetic factors can predispose a person to obesity, as well as influence the effectiveness of weight-loss strategies. The body relies on cells to process and store energy, and changes in genes that regulate these functions can cause an imbalance that leads to excessive energy storage and weight gain.

The BDNF protein plays several roles in the brain and nervous system and, at high levels, the protein can stimulate the feeling of fullness.

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, T and C, of each gene, inheriting one copy from each parent.

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.

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