Calorie control weight-loss may depend on genes

Dieters who fail to lose weight on a calorie-controlled diet may take heart at new research from Tufts University, which indicates that it may be down to their genes.

The researchers have identified a variant in the perilipin gene PLIN 11482. This gene controls the production of a protein called perilipin, which regulates the release of fat from cells.

An earlier study suggested that the variant, minor A allele, was linked to a lower risk of obesity in the first place. The latest evidence, published in the Journal of Clinical Endocrinology and Metabolism (2005; 90 (9): 5121-5126) supports this, but it also indicates that if minor A allele carriers do become obese, some may be resistant to weight loss through calorie restriction.

Forty-eight severely obese patients (body mass index 34 to 50) completed the intervention, which involved sticking to a low-energy diet for one year. Their body weight was measured at the start, and three, six and 12 months into the trial.

The 15 minor A allele carriers tended to have a lower body weight than the 33 participants with the more common G variant at the start of the study.

But while members of the G group lost an average of 20 pounds over the year, in the minor A allele group weight loss was not significant.

The researchers said that the difference in the groups' body weight at the start of the study could not explain the weight loss results.

Rather, Jose Ordovas, one of the study authors, said: "It is as if the connection between calorie intake and body weight is interrupted.

Carriers of this gene variant appear to have more stable mechanisms for controlling their body weight. In people that have become obese, this leads to a blunting of the weight-loss effect we would expect to see with calorie restriction."

The researchers concluded that the carriers of the minor A allele variant were resistant to weight loss, and that polymorphism could predict whether or not weight-loss strategies based on low-energy diets were likely to work.

However the researchers cautioned that the study was carried out in Spain with participants of the same general ethnicity. The findings may not necessarily hold true for other ethnic groups in other countries.

Although he said that research in the field is not yet at a stage where nutritional genomics could make a significant contribution to weight loss, Ordovas maintains that the new findings could contribute to future strategies for weigh control.