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Nutritional genomics identifies a potential weight-loss resistance gene

Two obese people follow the same low-calorie diet and do not exercise, but one loses much more weight than the other. Genetic factors may explain this phenomenon, according to Jos Ordovas, PhD, director of the Nutrition and Genomics Laboratory at the Jean Mayer USDA Human Nutrition Research Center on Aging (HNRCA) at Tufts University. In a study published in the Journal of Clinical Endocrinology & Metabolism, Ordovas and colleagues identified a variation in the perilipin gene that appears to render some people resistant to weight loss from calorie restriction. This research builds on their earlier work on perilipin and obesity.

"It is as if the connection between calorie intake and body weight is interrupted," explains Ordovas, who is also a professor at the Friedman School of Nutrition Science and Policy at Tufts. "Carriers of this gene variant appear to have more stable mechanisms for controlling their body weight," Ordovas says. "In people that have become obese, this leads to a blunting of the weight-loss effect we would expect to see with calorie restriction."

Andrew Greenberg, MD, director of the Obesity and Metabolism Laboratory at the USDA Center at Tufts, one of the scientists who discovered perilipin, notes that in an earlier study this same gene variant was linked with a lower risk of obesity, but in this study, it was associated with weight loss resistance.

"It may make sense," Greenberg says, "if we consider that this perilipin gene variant induces a sort of buffer against changes in how the body burns and stores food energy. It appears to protect against weight gain in lean women, while preventing weight loss in men and women who have become obese."

The clinical study was led by Dolores Corella, PhD, of the Genetic and Molecular Epidemiology Unit, University of Valencia, in Spain, who is a visiting scientist at the HNRCA and a long-term collaborator with Ordovas. These in
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Contact: Siobhan Gallagher
617-636-6586
Tufts University
7-Dec-2005


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