Genetic discoveries link obesity to the brain

Obesity may have more to do with how the brain eoperates than how food is digested, according to a pair of papers published in the January issue of Nature Genetics (link).

Multinational teams led by deCODE genetics in Reykjavik, Iceland, and the U.S. Genetic Investigation of Anthropometric Traits consortium analyzed the genomes of more than 120,000 people. The paper from deCODE researchers identified variants at seven loci. The one from the consortium found six, and the effect of the genes differed by age.

"In younger children, ages 5-10, we found that with three of the genes the children were already heavier at that young age, and, with the other three genes, we saw that there was no effect on children," said Gonçalo Abecasis, DPhil, one of the leaders of the consortium and associate professor at the University of Michigan School of Public Health in Ann Arbor. "For those [genes] we only saw an effect in much older individuals. This points to different mechanisms influencing your weight at different ages."

Most of these genes are activated in the brain, with several working in the hypothalamus. Investigators say this is important to provide direction for research than could lead to drug therapies to treat obesity.

"This suggests that, as we work to develop better means of combating obesity, including using these discoveries as the first step in developing new drugs, we need to focus on the regulation of appetite at least as much as on the metabolic factors of how the body uses and stores energy," said Dr. Kári Stefánsson, deCODE's CEO.

But those behind this work also expressed caution because, for most people, each gene plays only a small role in weight, and there are many more to be discovered. For example, researchers estimate that those carrying the most genes with an increased obesity risk would tend to be 10 pounds heavier than those who have the fewest.