Excessive fuel availability amplifies the FTO-mediated obesity risk: Results from the TUEF and Whitehall II studies

Róbert Wagner; Ádám G. Tabák; Ellen Fehlert; Louise Fritsche; Benjamin A. Jaghutriz; Róbert J. Bánhegyi; Sebastian M. Schmid; Harald Staiger; Fausto MacHicao; Andreas Peter; Hans Ulrich Häring; Andreas Fritsche; Martin Heni

doi:10.1038/s41598-017-15744-4

Excessive fuel availability amplifies the FTO-mediated obesity risk: Results from the TUEF and Whitehall II studies

Róbert Wagner, Ádám G. Tabák, Ellen Fehlert, Louise Fritsche, Benjamin A. Jaghutriz, Róbert J. Bánhegyi, Sebastian M. Schmid, Harald Staiger, Fausto MacHicao, Andreas Peter, Hans Ulrich Häring, Andreas Fritsche, Martin Heni^*

^*Corresponding author for this work

Clinic of Internal Medicine I

7 Citations (Scopus)

Abstract

Variation in FTO is the most important common genetic determinant of body weight. Altered energy metabolism could underlie this association. We hypothesized that higher circulating glucose or triglycerides can amplify the FTO impact on BMI. In 2671 subjects of the TUEF study, we investigated the interaction effect of fasting glucose and triglyceride levels with rs9939609 in FTO on BMI. We analysed the same interaction effect by longitudinally utilizing mixed effect models in the prospective Whitehall II study. In TUEF, we detected an interaction effect between fasting glucose and fasting triglycerides with rs9939609 on BMI (p = 0.0005 and p = 5 × 10 ^-7 , respectively). The effect size of one risk allele was 1.4 ± 0.3 vs. 2.2 ± 0.44 kg/m ² ; in persons with fasting glucose levels below and above the median, respectively. Fasting triglycerides above the median increased the per-allele effect from 1.4 ± 0.3 to 1.7 ± 0.4 kg/m ² . In the Whitehall II study, body weight increased by 2.96 ± 6.5 kg during a follow-up of 13.5 ± 4.6 yrs. Baseline fasting glucose and rs9939609 interacted on weight change (p = 0.009). Higher fasting glucose levels may amplify obesity-risk in FTO carriers and lead to an exaggerated weight gain over time. Since weight gain perpetuates metabolic alterations, this interplay may trigger a vicious circle that leads to obesity and diabetes.

Original language	English
Article number	15486
Journal	Scientific Reports
Volume	7
Issue number	1
ISSN	2045-2322
DOIs	https://doi.org/10.1038/s41598-017-15744-4
Publication status	Published - 01.12.2017

Funding

We gratefully acknowledge excellent technical assistance from Anja Dessecker, Ellen Kollmar, Andreas Vosseler, and Roman Werner, all from the Department of Internal Medicine, Division of Endocrinology, Diabetology, Nephrology, Vascular Disease and Clinical Chemistry, University Hospital, Eberhard Karls University, Tübingen. We thank all the women and men who participate in the TUEF and Whitehall II Studies, as well as all Whitehall II research scientists, study and data managers and clinical and administrative staff who made this study possible. The authors thank Shirley Würth (Eberhard Karls University Tübingen) for editorial assistance. This study was supported in part by a grant (01GI0925) from the Federal Ministry of Education and Research (BMBF) to the German Center for Diabetes Research (DZD e.V.). The UK Medical Research Council, British Heart Foundation, and the US National Institutes of Health (R01HL36310, R01AG013196) have supported collection of data in the Whitehall II Study.

Research Areas and Centers

Academic Focus: Center for Brain, Behavior and Metabolism (CBBM)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s41598-017-15744-4

Cite this

Wagner, R., Tabák, Á. G., Fehlert, E., Fritsche, L., Jaghutriz, B. A., Bánhegyi, R. J., Schmid, S. M., Staiger, H., MacHicao, F., Peter, A., Häring, H. U., Fritsche, A., & Heni, M. (2017). Excessive fuel availability amplifies the FTO-mediated obesity risk: Results from the TUEF and Whitehall II studies. Scientific Reports, 7(1), Article 15486. https://doi.org/10.1038/s41598-017-15744-4

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title = "Excessive fuel availability amplifies the FTO-mediated obesity risk: Results from the TUEF and Whitehall II studies",

abstract = " Variation in FTO is the most important common genetic determinant of body weight. Altered energy metabolism could underlie this association. We hypothesized that higher circulating glucose or triglycerides can amplify the FTO impact on BMI. In 2671 subjects of the TUEF study, we investigated the interaction effect of fasting glucose and triglyceride levels with rs9939609 in FTO on BMI. We analysed the same interaction effect by longitudinally utilizing mixed effect models in the prospective Whitehall II study. In TUEF, we detected an interaction effect between fasting glucose and fasting triglycerides with rs9939609 on BMI (p = 0.0005 and p = 5 × 10 -7 , respectively). The effect size of one risk allele was 1.4 ± 0.3 vs. 2.2 ± 0.44 kg/m 2 ; in persons with fasting glucose levels below and above the median, respectively. Fasting triglycerides above the median increased the per-allele effect from 1.4 ± 0.3 to 1.7 ± 0.4 kg/m 2 . In the Whitehall II study, body weight increased by 2.96 ± 6.5 kg during a follow-up of 13.5 ± 4.6 yrs. Baseline fasting glucose and rs9939609 interacted on weight change (p = 0.009). Higher fasting glucose levels may amplify obesity-risk in FTO carriers and lead to an exaggerated weight gain over time. Since weight gain perpetuates metabolic alterations, this interplay may trigger a vicious circle that leads to obesity and diabetes. ",

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Wagner, R, Tabák, ÁG, Fehlert, E, Fritsche, L, Jaghutriz, BA, Bánhegyi, RJ, Schmid, SM, Staiger, H, MacHicao, F, Peter, A, Häring, HU, Fritsche, A & Heni, M 2017, 'Excessive fuel availability amplifies the FTO-mediated obesity risk: Results from the TUEF and Whitehall II studies', Scientific Reports, vol. 7, no. 1, 15486. https://doi.org/10.1038/s41598-017-15744-4

TY - JOUR

T1 - Excessive fuel availability amplifies the FTO-mediated obesity risk: Results from the TUEF and Whitehall II studies

AU - Wagner, Róbert

AU - Tabák, Ádám G.

AU - Fehlert, Ellen

AU - Fritsche, Louise

AU - Jaghutriz, Benjamin A.

AU - Bánhegyi, Róbert J.

AU - Schmid, Sebastian M.

AU - Staiger, Harald

AU - MacHicao, Fausto

AU - Peter, Andreas

AU - Häring, Hans Ulrich

AU - Fritsche, Andreas

AU - Heni, Martin

PY - 2017/12/1

Y1 - 2017/12/1

N2 - Variation in FTO is the most important common genetic determinant of body weight. Altered energy metabolism could underlie this association. We hypothesized that higher circulating glucose or triglycerides can amplify the FTO impact on BMI. In 2671 subjects of the TUEF study, we investigated the interaction effect of fasting glucose and triglyceride levels with rs9939609 in FTO on BMI. We analysed the same interaction effect by longitudinally utilizing mixed effect models in the prospective Whitehall II study. In TUEF, we detected an interaction effect between fasting glucose and fasting triglycerides with rs9939609 on BMI (p = 0.0005 and p = 5 × 10 -7 , respectively). The effect size of one risk allele was 1.4 ± 0.3 vs. 2.2 ± 0.44 kg/m 2 ; in persons with fasting glucose levels below and above the median, respectively. Fasting triglycerides above the median increased the per-allele effect from 1.4 ± 0.3 to 1.7 ± 0.4 kg/m 2 . In the Whitehall II study, body weight increased by 2.96 ± 6.5 kg during a follow-up of 13.5 ± 4.6 yrs. Baseline fasting glucose and rs9939609 interacted on weight change (p = 0.009). Higher fasting glucose levels may amplify obesity-risk in FTO carriers and lead to an exaggerated weight gain over time. Since weight gain perpetuates metabolic alterations, this interplay may trigger a vicious circle that leads to obesity and diabetes.

AB - Variation in FTO is the most important common genetic determinant of body weight. Altered energy metabolism could underlie this association. We hypothesized that higher circulating glucose or triglycerides can amplify the FTO impact on BMI. In 2671 subjects of the TUEF study, we investigated the interaction effect of fasting glucose and triglyceride levels with rs9939609 in FTO on BMI. We analysed the same interaction effect by longitudinally utilizing mixed effect models in the prospective Whitehall II study. In TUEF, we detected an interaction effect between fasting glucose and fasting triglycerides with rs9939609 on BMI (p = 0.0005 and p = 5 × 10 -7 , respectively). The effect size of one risk allele was 1.4 ± 0.3 vs. 2.2 ± 0.44 kg/m 2 ; in persons with fasting glucose levels below and above the median, respectively. Fasting triglycerides above the median increased the per-allele effect from 1.4 ± 0.3 to 1.7 ± 0.4 kg/m 2 . In the Whitehall II study, body weight increased by 2.96 ± 6.5 kg during a follow-up of 13.5 ± 4.6 yrs. Baseline fasting glucose and rs9939609 interacted on weight change (p = 0.009). Higher fasting glucose levels may amplify obesity-risk in FTO carriers and lead to an exaggerated weight gain over time. Since weight gain perpetuates metabolic alterations, this interplay may trigger a vicious circle that leads to obesity and diabetes.

UR - https://www.scopus.com/pages/publications/85034069171

U2 - 10.1038/s41598-017-15744-4

DO - 10.1038/s41598-017-15744-4

M3 - Journal articles

AN - SCOPUS:85034069171

SN - 2045-2322

VL - 7

JO - Scientific Reports

JF - Scientific Reports

IS - 1

M1 - 15486

ER -

Excessive fuel availability amplifies the FTO-mediated obesity risk: Results from the TUEF and Whitehall II studies

Abstract

Funding

Research Areas and Centers

UN SDGs

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