Exercise Weakens Effect of FTO Obesity Gene, Study Confirms

Veronica Hackethal, MD

May 02, 2017

A new study has highlighted the importance of physical activity, even among those who are at higher risk of being obese because they carry the FTO gene variant.

By exercising, such individuals may be able to dampen down, by about a third, the FTO gene's effects on their body mass index (BMI), according to the findings, published online last week in PLOS Genetics, by Mariaelisa Graff, PhD, of the University of North Carolina at Chapel Hill, and colleagues.

This discovery replicates prior demonstrations that exercise can mitigate the effects of the FTO gene (PLoS Genet. 2013; DOI:10.1371/journal.pgen.1003607; PLoS Med. 2010; DOI:10.1371/journal.pmed.1000332), say the researchers.

And by using physical exercise as a covariate for statistical adjustment, the researchers were also able to unearth 11 new genes associated with obesity.

"Our study revealed 11 completely new obesity genes, suggesting that in future studies, accounting for physical activity and other important lifestyle factors could boost the search for new obesity genes," Dr Graff commented in a press release from her institution.

Hunting for New Gene Variants Linked to Obesity

While unhealthy eating and inactivity are thought to be the major contributors to the global obesity epidemic, some people are genetically more susceptible to overweight and obesity than others. Among obesity-related genes discovered to date, FTO has the strongest association with increased BMI.

But prior research reported by Medscape Medical News has shown that those carrying the FTO gene still respond to weight-loss treatments that use diet, physical activity, or medication.

In their new paper, Dr Graff and colleagues set out to pinpoint genetic variants whose effects on adiposity are modified by physical activity.

They used a meta-analysis of 60 studies in 200,452 adults of European (n=180,423) or other ancestry (n=20,029) which included 2.5 million genetic variants. Twenty-three percent of subjects were considered physically inactive, while 77% were considered physically active.

The studies evaluated relationships between genes, physical activity, BMI, and waist circumference or waist-to-hip ratio.

Results showed that physical activity was associated with a 33% weakening of the effect of the FTO gene, confirming the findings of the previous studies. The authors note that the mechanism underlying the FTO gene's sensitivity to physical activity remains unclear, however.

Analyses not adjusted for physical activity failed to find any other genetic variants whose activity was sensitive to exercise, but adjusting for physical activity identified 11 new obesity-related genetic variants, one of which was weakened by up to 71% in active vs inactive individuals.

The results indicate that future obesity-gene discovery studies should take into account physical activity and other environmental factors, stress Dr Graff and colleagues.

But "a weakness of our study was that the participants self-reported their physical-activity habits rather than being surveyed objectively," Dr Graff observed.

"To identify more genes whose effects are either dampened or amplified by physical activity, we need to carry out larger studies with more accurate measurement of physical levels," she concluded.

Funding for the studies and conflicts of interest are listed in the paper.

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PLoS Genet. Published online April 27, 2017. Article

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