May 2024
Why do some people develop obesity despite high levels of physical activity?

Genetic predisposition might explain some of the variability in response to exercise.

We know that exercise levels alone do not fully explain a person’s tendency to obesity. To explore the potential genetic basis for at least some of this variability, investigators used step count and genetic data from an existing US population-based data set. Genetic risk for obesity was determined by using known loci from a prior genome-wide association study to create quartiles of polygenic risk score for 3100 adults (median age, 53 years) of European ancestry who were not obese at baseline (median body-mass index, about 24.5 kg/m2).

Participants walked a median 8300 steps daily at baseline and were followed for a median 5.4 years, during which obesity developed in 13% of those in the lowest polygenic risk score quartile and 43% in the highest quartile. Both step count and polygenic risk score quartile were correlated with risk for developing obesity. For example, participants at the 75th percentile of polygenic risk score risk needed to walk 2280 more steps daily than participants at the 50th percentile to have the same relative risk reduction. Conversely, participants at the 25th percentile needed to walk 3660 fewer steps daily than those at the 50th percentile for the same relative risk reduction.

Comment: The authors acknowledge that dietary intake is an important contributor to obesity that this analysis does not address. The analysis was strengthened by excluding participants whose obesity developed within six months of study entry, which reduced but did not eliminate the possibility for reverse causality as an explanation. The fact that these results apply only to patients of European ancestry also is a limitation. Despite these caveats, these results can help clinicians explain to patients why not all steps are equal. A patient whose weight increases despite following the usual recommendation of 8000 to 10,000 steps daily (and therefore might have a high polygenic risk score) might need to increase activity by 3000 to 4000 additional steps daily.

Thomas L. Schwenk, MD, Professor Emeritus, Family and Community Medicine, University of Nevada School of Medicine, Reno, USA.

Brittain EL, et al. Physical activity and incident obesity across the spectrum of genetic risk for obesity. JAMA Netw Open 2024; 7: e243821.

This summary is taken from the following Journal Watch titles: General Medicine, Ambulatory Medicine.

JAMA Netw Open