Physical Activity and Insulin Sensitivity Independently Attenuate the Effect of FTO rs9939609 on Obesity
Authors' conclusion
Greater PA and IS independently reduced the effect of rs9939609 on obesity. These effects might be mediated through altered expression of FTO in skeletal muscle. Our results indicated that PA and/or other means of increasing insulin sensitivity could counteract FTO-related genetic predisposition to obesity.
Study context
- Population
- Up to 19,585 individuals; Physical activity (PA) self-reported, insulin sensitivity (IS) based on inverted HOMA insulin resistance index; muscle biopsies from 140 menup to
- Participants
- 19,585 participants
- Comparison
- Effect of FTO rs9939609 A allele on BMI by high vs low PA and IS
- Outcome
- Interaction of PA and IS with the BMI-increasing effect of the FTO rs9939609 A allele
Methodological detailsgene–environment interaction analyses, functional analyses in muscle biopsies and cultured muscle cells
- Gene–environment interaction analyses
- Functional analyses in muscle biopsies and cultured muscle cells
Main finding
As reported in the abstract
BMI effect of FTO rs9939609 A allele
- Attenuation with high PA: 47%; β (SE) −0.32 (0.10) kg/m²
- P = 0.0013
- Attenuation with high IS: 51%; β (SE) −0.31 (0.09) kg/m²
- P = 0.00028
- Independent interaction, PA: β (SE) −0.20 (0.09) kg/m²
- P = 0.023
- Independent interaction, IS: β (SE) −0.28 (0.09) kg/m²
- P = 0.0011
Further findings
All-cause mortality and certain cardiometabolic outcomes with rs9939609 A allele
- HR, 1.07-1.20
- P > 0.04
- Effects tended to be weakened by greater PA and IS
FTO expression in skeletal muscle tissue with rs9939609 A allele
- Higher expression: 0.03 (0.01)
- P = 0.011
- Physical interaction between FTO promoter and enhancer region encompassing rs9939609 in skeletal muscle cells
Original publication
Physical Activity and Insulin Sensitivity Independently Attenuate the Effect of FTO rs9939609 on Obesity. Diabetes Care. Published 21 February 2023. doi:10.
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