Genes May Predict Fat Risk

GENERIC Overweight man, health obesity
How well your jeans fit may be up to your genes.

The actions of three specific genes determine how many fat cells you have — and whether these fat cells make you apple shaped or pear shaped. The findings come from researchers at Harvard's Joslin Diabetes Center in Boston and the University of Leipzig in Germany.

"By looking at your genes, we can tell how fat you are and how your body fat will be distributed," says Joslin President and Harvard professor C. Ronald Kahn, MD, in a news release. The study findings appear in the April 10 early online edition of the Proceedings of the National Academy of Sciences.

Kahn and colleagues used new gene-chip technology to look for genes and gene activity in abdominal fat — the kind of fat linked to disease — and under-the-skin fat. They started by studying mice. Their initial results were so striking, they went on to test people.

Kahn's team got fat samples from nearly 200 people. Some were normal weight, some were obese, and some were very obese. Some had fat accumulation in the buttocks and thighs (under-the-skin) — the pear shape linked to fewer health problems. Some had fat accumulation in the belly (abdominal) — the apple shape linked to diabetes, stroke, and heart disease.

3 Genes Govern Fat

The researchers identified three genes that had major effects on how much fat a person had and on where that fat piled up. The genes — T-box 15 (Tbx15), glypican 4 (Gpc4), and homeo box A5 (HoxA5) — are very important in the early development of the embryo. They play major roles in body pattern, face formation, and skeletal development.

"What is clear is that multiple developmental genes … exhibit dramatic differences in the level of expression of [fat cells and cells that become fat cells] from different regions of the body," Kahn and colleagues write. "One of the most striking features of the expression of HoxA5, Gpc4, and Tbx15 in human [fat] is not only their [different levels of action in different fat deposits] but also their strong correlation with body mass index."

The researchers suggest that these genes play a major role in determining whether a person becomes obese.

Are genes destiny? Most scientists don't think it's necessarily so. Environmental factors — including lifestyle — affect gene activity. But Kahn says it's too soon to know whether people can change what their fat genes dictate.

"While we now can predict the fat pattern, we have no magic bullet to alter the outcome," he says. "With these new findings, we have identified potential targets for perhaps one day changing body shape. We don't have drugs to alter the pattern now, but perhaps in the future we will."

SOURCES: Gesta, S. Proceedings of the National Academy of Science, April 10, 2006 early online edition. News release, Joslin Diabetes Center, Boston.

By Daniel J. DeNoon
Reviewed by Louise Chang, M.D.
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