Diabetes Gene May Have Links to Obesity
The discovery of a gene believed to be connected to morbid obesity began as an exploration into the causes of Type I diabetes.
The discovery, published in the journal Public Library of Science, was made by researchers originally from Sweden and France who collaborated at the UW.
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| Dr. Åke Lernmark (left) in the Molecular and Genetics Core Lab of the Diabetes Research Center with fellow scientists Libby Rutledge (center) and Armand McMurray (right). |
The gene, on chromosome 10, was first linked 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 incidences of Type I diabetes in the world.
In 1997, Lernmark was joined in his UW laboratory by Dr. Philippe Froguel, a Poll Visiting Scholar.
Froguel, senior author of the research, is based at Imperial College London, and Hammersmith Hospital, London. He carried out the research while at the Institut Pasteur de Lille in France. Froguel's group had previously determined that obese people often had genetic variations in Chromosome 10, with individual variations showing up in the GAD2 gene.
The researchers believe that GAD2 produces the protein GAD65 that, in the hypothalamus, catalyzes the production of a neurotransmitter that stimulates or suppresses appetite.
Several years ago, Lernmark and his colleagues in Sweden found that some obese people had antibodies to GAD65. This finding remained unexplained, but sparked Froguel's interest when he was searching chromosome 10 for an obesity gene candidate.
Lernmark said that it was a pleasant surprise for both groups when it turned out that GAD2 gene was the candidate. Research may help to untangle the role of GAD65 in obesity, he said.
Froguel's group screened 575 obese people and 646 non-obese people in France and found a connection between variations in the GAD2 gene and obesity.
Obese people with two particular variations in their GAD2 genes had more difficulty controlling food intake as measured by a standard survey of eating behavior.
Lernmark, a co-author, cautions that researchers are far from any genetic treatment of obesity. He says obesity results from the interaction of a variety of genes and environmental factors, such as nutrient intake and physical activity. Lernmark said he hopes there will be further research on genetic connections to obesity. Meanwhile, research continues in the Lernmark lab and in other labs across the country about the effect of GAD2 on diabetes.
Development note Dr. Åke Lernmark holds the Robert H. Williams Endowed Chair in Medicine, an appointment that provides funds vital to his work. Created by donors, such endowed chairs and professorships provide resources in perpetuity for research and other essential activities. |