Physical Activity Overcomes Genetic Predisposition for Obesity

Individuals who have a genetic mutation associated with high body mass index (BMI) may be able to offset their increased risk for obesity through physical activity, according to a report in the September 8 issue of Archives of Internal Medicine, one of the JAMA/Archives journals.

There is a widely acknowledged genetic component to BMI and obesity, according to background information in the article. Recently, a strong association has been shown between BMI and variants of one gene, known as the fat mass and obesity associated (FTO) gene. The mutations associated with obesity are present in about 30 percent of European populations and are associated with a 1.75-kilogram (about 3.9 pounds) increase in body weight. Lifestyle factors such as diet and physical activity are also important contributors to weight gain, but it is unknown exactly how they interact with genetics.

Evadnie Rampersaud, M.S.P.H., Ph.D., then of the University of Maryland School of Medicine in Baltimore and now of the University of Miami, and colleagues analyzed DNA samples of 704 healthy Amish adults (average age 43.6, 53 percent men and 47 percent women) recruited from 2003 to 2007. Participants also underwent a series of physiological tests, including a seven-day measurement of physical activity using an instrument known as an accelerometer.

A total of 54 percent of the men and 63.7 percent of the women were overweight, and 10.1 percent of the men and 30.5 percent of the women were obese. In the genetic analysis, 26 single-nucleotide polymorphisms (SNPs, or changes in a single base letter of DNA) in the FTO gene were associated with BMI.

The researchers then divided participants into two groups based on their physical activity levels and assessed the relationship between BMI and the two strongest SNPs. Both SNPs were associated with BMI only in individuals who had low physical activity scores for their age and sex; they had no effect on those with above-average physical activity scores.

“Activity levels in the ‘high-activity’ stratum were approximately 900 calories [860 calories for women and 980 calories for men] higher than in the ‘low-activity’ stratum, which, depending on body size, corresponds to about three to four hours of moderately intensive physical activity, such as brisk walking, house cleaning or gardening,” the authors write.

“In conclusion, we have replicated the associations of common SNPs in the FTO gene with increased BMI and risk to obesity in the Old Order Amish,” they conclude. “Furthermore, we provide quantitative data to show that the weight increase resulting from the presence of these SNPs is much smaller and not statistically significant in subjects who are very physically active. This finding offers some clues to the mechanism by which FTO influences changes in BMI and may have important implications in targeting personalized lifestyle recommendations to prevent obesity in genetically susceptible individuals.”(Arch Intern Med. 2008;168[16]:1791-1797. Available pre-embargo to the media at jamamedia.org.)