Physical Activity and Insulin Sensitivity Independently Attenuate the Effect of FTO rs9939609 on Obesity

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Physical Activity and Insulin Sensitivity Independently Attenuate the Effect of FTO rs9939609 on Obesity. / Andersen, Mette K; Ängquist, Lars; Bork-Jensen, Jette; Jonsson, Anna E; Stinson, Sara E; Sandholt, Camilla H; Thodberg, Malte; Pikkupeura, Laura Maarit; Ongstad, Emily L.; Grarup, Niels; Astrup, Arne; Pedersen, Oluf; Williams, Kristine; Barrès, Romain; Sørensen, Thorkild I A; Linneberg, Allan; Grimsby, Joseph; Rhodes, Christopher J; Hansen, Torben.

In: Diabetes Care, Vol. 46, No. 5, 2023, p. 985–992.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Andersen, MK, Ängquist, L, Bork-Jensen, J, Jonsson, AE, Stinson, SE, Sandholt, CH, Thodberg, M, Pikkupeura, LM, Ongstad, EL, Grarup, N, Astrup, A, Pedersen, O, Williams, K, Barrès, R, Sørensen, TIA, Linneberg, A, Grimsby, J, Rhodes, CJ & Hansen, T 2023, 'Physical Activity and Insulin Sensitivity Independently Attenuate the Effect of FTO rs9939609 on Obesity', Diabetes Care, vol. 46, no. 5, pp. 985–992. https://doi.org/10.2337/dc22-2078

APA

Andersen, M. K., Ängquist, L., Bork-Jensen, J., Jonsson, A. E., Stinson, S. E., Sandholt, C. H., Thodberg, M., Pikkupeura, L. M., Ongstad, E. L., Grarup, N., Astrup, A., Pedersen, O., Williams, K., Barrès, R., Sørensen, T. I. A., Linneberg, A., Grimsby, J., Rhodes, C. J., & Hansen, T. (2023). Physical Activity and Insulin Sensitivity Independently Attenuate the Effect of FTO rs9939609 on Obesity. Diabetes Care, 46(5), 985–992. https://doi.org/10.2337/dc22-2078

Vancouver

Andersen MK, Ängquist L, Bork-Jensen J, Jonsson AE, Stinson SE, Sandholt CH et al. Physical Activity and Insulin Sensitivity Independently Attenuate the Effect of FTO rs9939609 on Obesity. Diabetes Care. 2023;46(5):985–992. https://doi.org/10.2337/dc22-2078

Author

Andersen, Mette K ; Ängquist, Lars ; Bork-Jensen, Jette ; Jonsson, Anna E ; Stinson, Sara E ; Sandholt, Camilla H ; Thodberg, Malte ; Pikkupeura, Laura Maarit ; Ongstad, Emily L. ; Grarup, Niels ; Astrup, Arne ; Pedersen, Oluf ; Williams, Kristine ; Barrès, Romain ; Sørensen, Thorkild I A ; Linneberg, Allan ; Grimsby, Joseph ; Rhodes, Christopher J ; Hansen, Torben. / Physical Activity and Insulin Sensitivity Independently Attenuate the Effect of FTO rs9939609 on Obesity. In: Diabetes Care. 2023 ; Vol. 46, No. 5. pp. 985–992.

Bibtex

@article{95b71937047e497688da4f0abd71e43d,

title = "Physical Activity and Insulin Sensitivity Independently Attenuate the Effect of FTO rs9939609 on Obesity",

abstract = "OBJECTIVE: The association between FTO rs9939609 and obesity is modified by physical activity (PA) and/or insulin sensitivity (IS). We aimed to assess whether these modifications are independent, whether PA and/or IS modify the association between rs9939609 and cardiometabolic traits, and to elucidate underlying mechanisms.RESEARCH DESIGN AND METHODS: Genetic association analyses comprised up to 19,585 individuals. PA was self-reported, and IS was defined based on inverted HOMA insulin resistance index. Functional analyses were performed in muscle biopsies from 140 men, and in cultured muscle cells.RESULTS: The BMI-increasing effect of the FTO rs9939609 A allele was attenuated by 47% with high PA (β [SE], -0.32 [0.10] kg/m2, P = 0.0013), and by 51% with high IS (-0.31 [0.09] kg/m2, P = 0.00028). Interestingly, these interactions were essentially independent (PA, -0.20 [0.09] kg/m2, P = 0.023; IS, -0.28 [0.09] kg/m2, P = 0.0011). The rs9939609 A allele was also associated with higher all-cause mortality and certain cardiometabolic outcomes (hazard ratio, 1.07-1.20, P > 0.04), and these effects tended to be weakened by greater PA and IS. Moreover, the rs9939609 A allele was associated with higher expression of FTO in skeletal muscle tissue (0.03 [0.01], P = 0.011), and in skeletal muscle cells, we identified a physical interaction between the FTO promoter and an enhancer region encompassing rs9939609.CONCLUSIONS: 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.",

author = "Andersen, {Mette K} and Lars {\"A}ngquist and Jette Bork-Jensen and Jonsson, {Anna E} and Stinson, {Sara E} and Sandholt, {Camilla H} and Malte Thodberg and Pikkupeura, {Laura Maarit} and Ongstad, {Emily L.} and Niels Grarup and Arne Astrup and Oluf Pedersen and Kristine Williams and Romain Barr{\`e}s and S{\o}rensen, {Thorkild I A} and Allan Linneberg and Joseph Grimsby and Rhodes, {Christopher J} and Torben Hansen",

note = "{\textcopyright} 2023 by the American Diabetes Association.",

year = "2023",

doi = "10.2337/dc22-2078",

language = "English",

volume = "46",

pages = "985–992",

journal = "Diabetes Care",

issn = "1935-5548",

publisher = "American Diabetes Association",

number = "5",

}

RIS

TY - JOUR

T1 - Physical Activity and Insulin Sensitivity Independently Attenuate the Effect of FTO rs9939609 on Obesity

AU - Andersen, Mette K

AU - Ängquist, Lars

AU - Bork-Jensen, Jette

AU - Jonsson, Anna E

AU - Stinson, Sara E

AU - Sandholt, Camilla H

AU - Thodberg, Malte

AU - Pikkupeura, Laura Maarit

AU - Ongstad, Emily L.

AU - Grarup, Niels

AU - Astrup, Arne

AU - Pedersen, Oluf

AU - Williams, Kristine

AU - Barrès, Romain

AU - Sørensen, Thorkild I A

AU - Linneberg, Allan

AU - Grimsby, Joseph

AU - Rhodes, Christopher J

AU - Hansen, Torben

PY - 2023

Y1 - 2023

N2 - OBJECTIVE: The association between FTO rs9939609 and obesity is modified by physical activity (PA) and/or insulin sensitivity (IS). We aimed to assess whether these modifications are independent, whether PA and/or IS modify the association between rs9939609 and cardiometabolic traits, and to elucidate underlying mechanisms.RESEARCH DESIGN AND METHODS: Genetic association analyses comprised up to 19,585 individuals. PA was self-reported, and IS was defined based on inverted HOMA insulin resistance index. Functional analyses were performed in muscle biopsies from 140 men, and in cultured muscle cells.RESULTS: The BMI-increasing effect of the FTO rs9939609 A allele was attenuated by 47% with high PA (β [SE], -0.32 [0.10] kg/m2, P = 0.0013), and by 51% with high IS (-0.31 [0.09] kg/m2, P = 0.00028). Interestingly, these interactions were essentially independent (PA, -0.20 [0.09] kg/m2, P = 0.023; IS, -0.28 [0.09] kg/m2, P = 0.0011). The rs9939609 A allele was also associated with higher all-cause mortality and certain cardiometabolic outcomes (hazard ratio, 1.07-1.20, P > 0.04), and these effects tended to be weakened by greater PA and IS. Moreover, the rs9939609 A allele was associated with higher expression of FTO in skeletal muscle tissue (0.03 [0.01], P = 0.011), and in skeletal muscle cells, we identified a physical interaction between the FTO promoter and an enhancer region encompassing rs9939609.CONCLUSIONS: 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.

AB - OBJECTIVE: The association between FTO rs9939609 and obesity is modified by physical activity (PA) and/or insulin sensitivity (IS). We aimed to assess whether these modifications are independent, whether PA and/or IS modify the association between rs9939609 and cardiometabolic traits, and to elucidate underlying mechanisms.RESEARCH DESIGN AND METHODS: Genetic association analyses comprised up to 19,585 individuals. PA was self-reported, and IS was defined based on inverted HOMA insulin resistance index. Functional analyses were performed in muscle biopsies from 140 men, and in cultured muscle cells.RESULTS: The BMI-increasing effect of the FTO rs9939609 A allele was attenuated by 47% with high PA (β [SE], -0.32 [0.10] kg/m2, P = 0.0013), and by 51% with high IS (-0.31 [0.09] kg/m2, P = 0.00028). Interestingly, these interactions were essentially independent (PA, -0.20 [0.09] kg/m2, P = 0.023; IS, -0.28 [0.09] kg/m2, P = 0.0011). The rs9939609 A allele was also associated with higher all-cause mortality and certain cardiometabolic outcomes (hazard ratio, 1.07-1.20, P > 0.04), and these effects tended to be weakened by greater PA and IS. Moreover, the rs9939609 A allele was associated with higher expression of FTO in skeletal muscle tissue (0.03 [0.01], P = 0.011), and in skeletal muscle cells, we identified a physical interaction between the FTO promoter and an enhancer region encompassing rs9939609.CONCLUSIONS: 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.

U2 - 10.2337/dc22-2078

DO - 10.2337/dc22-2078

M3 - Journal article

C2 - 36809463

VL - 46

SP - 985

EP - 992

JO - Diabetes Care

JF - Diabetes Care

SN - 1935-5548

IS - 5

ER -

ID: 339688220