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Integrative Biology

The growth hormone—IGF-I axis as a mediator for the association between FTO variants and body mass index: results of the Study of Health in Pomerania

International Journal of Obesity volume 35, pages 364–372 (2011)Cite this article

Subjects

Abstract

Context:

Risk alleles of the fat mass- and obesity-associated gene (FTO) are related not only to increased body mass index (BMI) values but also to mortality. It was speculated that cellular effects of the FTO gene affect most organs, especially their ability to maintain or regenerate proper function when afflicted by various diseases. FTO is highly expressed in the hypothalamus and also in the pituitary gland. The decrease in growth hormone (GH) secretion is known to cause a decrease in lean body mass in older subjects.

Objective:

We hypothesized an association of rs9926289 with insulin-like growth factor (IGF)-I.

Design and setting:

Cross-sectional data from the Study of Health in Pomerania, a population-based study in the northeastern part of Germany, were used.

Participants:

For the final analyses, 3882 subjects aged 20–79 years were available.

Main outcome measures:

Continuous IGF-I, low IGF-I according to clinically meaningful age- and gender-specific reference values, and BMI were used as outcome measures.

Results:

Over all age groups, a statistically significant relationship between FTO and IGF-I was found. In subjects younger than 55 years of age, homozygous carriers of the FTO risk allele exhibited lower serum IGF-I levels adjusted for 5-year age groups, gender and IGF-I binding protein 3 levels (linear regression, coefficient±s.e. for FTO AA genotype:−8.6±2.8; P=0.002). Further adjustments for obesity and diabetes did not suspend this association (coefficient:–7.8; P=0.005). As expected, the FTO AA genotype effect on BMI was reduced from 0.76 to 0.62 kg m−2 by including IGF-I. No relationship between FTO and IGF-I levels was found in subjects aged 55 years or older (−2.7±2.4; P=0.260 for FTO AA genotype adjusted for age, gender and IGF-I binding protein 3 levels).

Conclusion:

We propose that the GH—IGF-I axis is a mediator for the relationship between FTO and BMI.

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Acknowledgements

SHIP is part of the Community Medicine Net (http://ship.community–medicine.de) of the Ernst Moritz Arndt University of Greifswald, which is funded by grants from the German Federal Ministry of Education and Research (BMBF, Grant 01ZZ96030); the Ministry for Education, Research, and Cultural Affairs; and the Ministry for Social Affairs of the Federal State of Mecklenburg–West Pomerania. The contributions to data collection made by field workers, study physicians, ultrasound technicians, interviewers and computer assistants are gratefully acknowledged. The SHIP genotyping was supported by the future fund of the state government of Mecklenburg-Vorpommern (UG 07 034). Part of this work was funded by the German National GenomeResearch Network (NGFN 01GS08197). Pfizer provided partial grant support for the determination of IGF-I and IGFBP3 concentrations.

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Author notes

  1. D Rosskopf and C Schwahn: These two authors contributed equally to this work.

Authors and Affiliations

  1. Department of Pharmacology, Center for Pharmacology and Experimental Therapeutics, Ernst-Moritz-Arndt University, Greifswald, Germany

    D Rosskopf, F Neumann, A Bornhorst, C Rimmbach, M Mischke, S Wolf, I Geissler & H K Kroemer

  2. Institute for Clinical Chemistry and Laboratory Medicine, Ernst-Moritz-Arndt University, Greifswald, Germany

    C Schwahn, M Nauck, N Friedrich & H Wallaschofski

  3. Dentistry Clinic, Ernst-Moritz-Arndt University, Greifswald, Germany

    T Kocher

  4. Department of Psychiatry and Psychotherapy, Ernst-Moritz-Arndt University, Stralsund, Germany,

    H-J Grabe

  5. Department of Child and Adolescent Psychiatry, University of Duisburg-Essen, Essen, Germany,

    J Hebebrand

  6. Institute for Community Medicine, Ernst-Moritz-Arndt University, Greifswald, Germany

    H Völzke

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  1. D Rosskopf
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Correspondence to C Schwahn.

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Competing interests

The authors, apart from JH, have nothing do disclosure. JH received German national grants. He also received honoraria, but not directly related to this work, from Roche.

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Rosskopf, D., Schwahn, C., Neumann, F. et al. The growth hormone—IGF-I axis as a mediator for the association between FTO variants and body mass index: results of the Study of Health in Pomerania. Int J Obes 35, 364–372 (2011). https://doi.org/10.1038/ijo.2010.158

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