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UT Southwestern researchers identify gene responsible for a rare body-fat disorder

DALLAS May 1, 2002 An international team of researchers led by scientists at UT Southwestern Medical Center at Dallas have identified the gene that causes a rare body-fat disorder, a discovery that may ultimately expand the understanding of obesity-related illnesses.

The researchers report that the disorder, congenital generalized lipodystrophy (CGL), or the extreme lack of body fat at birth, occurs as a result of mutations in the AGPAT2 gene, which is involved in the production of fat. This is the first documented human disorder that disrupts the biochemical pathway of fat synthesis.

The study appears in the May issue of Nature Genetics.

Now we know why patients with congenital generalized lipodystrophy are unable to synthesize fat in a normal fashion, said Dr. Abhimanyu Garg, professor of internal medicine and chief of nutrition and metabolic diseases at UT Southwestern and senior author of the study. Even though this is a rare disease affecting approximately one in 12.5 million people, our findings may have implications to the understanding of insulin-resistance disorders and common forms of obesity.

Garg, a senior investigator in the Center for Human Nutrition, has been studying lipodystrophy patients referred from all over the world for the past 16 years.

The mutated form of the AGPAT2 gene was identified in the 11 families that participated in the study. Characterized by partial or complete lack of body fat at birth, individuals affected by this disorder develop severe diabetes as teen-agers. Other complications include severe insulin resistance, high blood lipids and an accumulation of fat in the liver.

Although we understand how an abnormal AGPAT2 gene may cause lack of body fat, we still need to study how the abnormal gene leads to severe insulin resistance, diabetes, high blood lipids and fatty liver, said Dr. Anil Agarwal, assistant professor of internal medicine and lead author of the study. <
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Contact: Amy Shields
Amy.Shields@UTSouthwestern.edu
214-648-3404
UT Southwestern Medical Center
1-May-2002


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