LB006 - FTO RS9939609 MODIFIES THE DOSE-RESPONSE ASSOCIATION BETWEEN PHYSICAL ACTIVITY METS AND OBESITY RISK

LB006

FTO RS9939609 MODIFIES THE DOSE-RESPONSE ASSOCIATION BETWEEN PHYSICAL ACTIVITY METS AND OBESITY RISK

D. Chermon¹, L. Kazarnovsky Nahshan¹, R. Birk^1,*

¹Department of Nutrition, Ariel University, Ariel, Israel

Rationale: Physical activity (PA) has been shown to attenuate the impact of the strongest known common FTO rs9939609 variant predisposed to common obesity. However, the PA quantified by standardized energetic cost is unknown. We aimed to study the association between FTO rs9939609 and PA levels using a quantitative standardized methodology of metabolic equivalent of task (METs) on obesity risk.

Methods: 5,824 adults' (69.5% female, mean 55.8±15.3 years) genotype and self-reported lifestyle questionnaires data were included in this cross-sectional study analysis. Individual PA levels were calculated using METs methodology. Logistic regression models were applied to assess associations between PA and obesity risk, stratified by FTO genotypes.

Results: FTO rs9939609 homozygosity (AA, 24.5%) was significantly associated with increased risk of obesity under a recessive model (OR=1.37; p<0.001). Each 100-unit increase in total METs was inversely associated with obesity risk across all FTO rs9939609 genotype groups, with ORs of 0.905  among TT carriers, 0.885 among AT carriers, and 0.856 among AA carriers. A significant additive FTO rs9939609 × total METs interaction was observed (OR=0.972), suggesting that the inverse association between METs and obesity risk became progressively stronger with each additional FTO risk allele. Carriers of FTO rs9939609 homozygosity (AA) exhibited higher BMI values across all levels of METs. Engagement in high-intensity PA (METs≥6) was associated with a 45% reduction in obesity risk among AA carriers (OR=0.552), and a 36% reduction in obesity risk among AT/TT genotypes (OR=0.640) compared to those engaging in lower intensity activities (METs<6).

Conclusion: FTO rs9939609 genotype-dependent is associated with energy metabolism intensity. Engagement in high-intensity PA (METs≥6) is associated with further significant reduction in obesity risk particularly in FTO rs9939609 risk carriers.

Disclosure of Interest: D. Chermon: None declared, L. Kazarnovsky Nahshan: None declared, R. Birk Consultant for: Scientific consultant