CAMBRIDGE, Mass. March 11, 1999 -- Millennium Pharmaceuticals, Inc. (Nasdaq: MLNM) has cloned the first gene that can suppress diet-induced obesity in mice. The gene may have strong implications in developing therapies to intervene in human obesity, the authors note in their report, which appears in the March 11, 1999 issue of Nature.
The scientists found that while the gene, called mahogany (mg), produces a protein (MG) in many tissues of the body, its activity in a specific region of the brain's hypothalamus is particularly interesting because of that region's role in body weight regulation.
"The cloning of the mahogany gene and the identification of its protein product are major first steps in achieving a better understanding of their roles in controlling weight based on the amount of fat in a diet," said Karen Moore, Ph.D., director of genetic systems at Millennium. Because of the great similarity between mouse and human metabolism, the scientists expect to find that the gene plays a similar role in people.
Mice with a mutation in their mg gene maintain a healthy weight whether they eat a high fat (42 percent fat) or low fat (9 percent fat) diet with the same amount of calories. In contrast, mice with a normal mg gene gain excess weight on the high fat diet. Such diet-induced obesity differs from forms of genetically-induced obesity in which weight gain occurs even when mice are fed a normal diet. Genetically induced obesity in mice has been linked to mutations in the obese (ob), diabetes (db), tubby (tub), fat (fat) and agouti-yellow (Ay) genes. Mice with a mutation in their mg gene can suppress the genetic induced obesity of agouti-yellow mice but not that of ob, db, tub and fat mice.
The structure of the large MG protein is complex and can occur in two major
forms. One form spans the cell wall leaving multiple sections of the protein to
project outside the cell, which may function as receptors to which small
proteins called peptide
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