November 03, 2003
GAD2 Gene Variation Increases Obesity

A variation of a gene called GAD2 was found to be more common among obese test subjects.

GAD2, which sits on chromosome 10, acts by speeding up production of a neurotransmitter in the brain called GABA, or gamma-amino butyric acid. When GABA interacts with another molecule named neuropeptide Y in a specific area of the brain - the paraventricular nucleus of the hypothalamus - we are stimulated to eat.

The researchers behind this study believe that people who carry a more active form of the GAD2 gene build up a larger than normal quantity of GABA in the hypothalamus, and suggest that this over accumulation of GABA drives the stimulus to eat further than normal, and is thus a basis for explaining why obese people overeat.

Professor Philippe Froguel, senior author of the research, from Imperial College London, and Hammersmith Hospital, London, and who carried out the research while at the Institut Pasteur de Lille, France, said: "The discovery that this one gene plays a role in determining whether someone is likely to overeat could be crucial in understanding the continued rise in obesity rates around the world.

"Genetic factors alone can not explain the rapid rise in obesity rates, but they may provide clues to preventative and therapeutic approaches that will ease the health burden associated with obesity.

"Having identified this gene, it may be possible to develop a screening programme to identify those who may be at risk of becoming obese later in life, and take effective preventative measures."

The team compared genome-wide scans of 576 obese and 646 normal weight adults in France, from which they identified two alternative forms, or alleles, of the GAD2 gene.

One form of the gene was found to be protective against obesity, while another increased the risk of obesity. The normal weight group of French adults had a higher frequency of the protective form of the GAD2 gene. Obesity is three to five times less prevalent in France than in the USA.

GAD2 codes for a protein involved in insulin metabolism.

The discovery, which will be published in an upcoming issue of the journal Public Library of Science (http://www.plos.org), involves researchers originally from Sweden and France who collaborated at the University of Washington in Seattle.

The gene, on Chromosome 10, was first connected to diabetes in 1991 by Dr. Åke Lernmark, R. H. Williams Professor of Medicine and adjunct professor of immunology at the UW. The GAD2 gene is responsible for the protein GAD65, which plays a role in the healthy use of insulin by the body. Lernmark is a native of Sweden, which has one of the highest rates of Type I diabetes incidence in the world.

If this result is confirmed in other populations expect GAD2 expression and the activity of the GAD6 protein to become targets for drug development.

Share |      Randall Parker, 2003 November 03 12:47 AM  Brain Genetics


Comments
jaed said at November 3, 2003 9:07 AM:

The second aspect (insulin metabolism) seems quite a bit more important than the first (overeating), unless someone's shown a general tendency on the part of obese people to eat more than non-obese people.

(Also, the part about Type I diabetes seems like a bit of a nonsequiter to me: insulin metabolization problems are implicated in Type II, which is often preceded by insulin resistance, but Type I isn't a problem with using insulin but a problem producing it.)

Bob Badour said at November 3, 2003 2:46 PM:

There are strong and obvious links between insulin metabolism and hunger. Elevated insulin and low blood glucose are a recipe for irresistible food cravings because the brain lacks a fuel source: no ketone bodies and no glucose. Elevated insulin inevitably causes low blood glucose.

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