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A new polymorphic site located in the human UCP1 gene controls the in vitro binding of CREB-like factor

International Journal of Obesity volume 26, pages 735–738 (2002)Cite this article

Abstract

Uncoupling protein 1 (UCP1) is uniquely expressed in brown adipose tissue (BAT) and generates heat by uncoupling respiration from ATP synthesis. A defect in BAT thermogenesis has been described in different models of rodent obesity. In humans, the implication of BAT in energy expenditure is still under discussion. A BclI polymorphism associated with fat gain over time has been described in the upstream region of the human UCP1 (hUCP1) gene. In this study, a new polymorphic site linked to the BclI site is described which results in a C to A point mutation, 89 bp downstream of the BclI site, ie at position −3737 bp. This site is located in the recently analysed regulatory region of the hUCP1 gene. The mutation disrupts a consensus site for the binding of ATF/CREB transcription factor family and inhibits the factor binding in vitro. However, transient transfection of a rodent brown adipocyte cell line shows that the isoproterenol (ISO) stimulation of the hUCP1 gene transcription is not significantly affected by this mutation. However, we postulate that the C/A substitution, in human, may contribute to a minor defect in the regulation of hUCP1 transcription and that would explain fat gain over time.

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Acknowledgements

We thank Dr K Clément for the gift of human DNA especially for the control population. We thank Dr F Fumeron for helpful discussion.

This work was supported in part by the Centre National de la Recherche Scientifique (CNRS), the Institut National de la Santé et de la Recherche Médicale (INSERM), the Association pour la Recherche contre le Cancer (ARC), the Human Frontier Science Program organization (HFSP), and the Institut de Recherches Servier.

M del Mar Gonzalez-Barroso was supported by a grant from the European Union (Marie Curie Mobility Training fellowship) and an associate researcher fellowship of the CNRS.

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  1. Centre de Recherches sur l'Endocrinologie Moléculaire et le Développement, CNRS, Meudon, France

    S Rousset, M del Mar Gonzalez-Barroso, C Gelly, C Pecqueur, F Bouillaud, D Ricquier & A-M Cassard-Doulcier

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  1. S Rousset
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  2. M del Mar Gonzalez-Barroso
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  3. C Gelly
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  4. C Pecqueur
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  5. F Bouillaud
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  6. D Ricquier
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  7. A-M Cassard-Doulcier
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Correspondence to A-M Cassard-Doulcier.

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Rousset, S., del Mar Gonzalez-Barroso, M., Gelly, C. et al. A new polymorphic site located in the human UCP1 gene controls the in vitro binding of CREB-like factor. Int J Obes 26, 735–738 (2002). https://doi.org/10.1038/sj.ijo.0801973

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