1. Institute for Animal Developmental and Molecular Biology, Heinrich Heine University, Universitätsstr. 1, D-40225 Düsseldorf, Germany
2. Department of Mouse Genetics and Metabolism, Institute for Genetics and Second Department of Internal Medicine,
3. Center of Molecular Medicine Cologne (CMMC) and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, D-50674 Cologne, Germany
4. Max-Planck Institute for the Biology of Ageing, D-50674 Cologne, Germany
5. These authors contributed equally to this work.
6. Present addresses: Department of Dermatology, Center of Molecular Medicine Cologne (CMMC), University of Cologne, D-50674 Cologne, Germany (J.V.); Epidauros Biotechnologie AG, D-82347 Bernried, Germany (T.P.).

Correspondence to: Jens C. Brüning^2,3,4Ulrich Rüther¹ Correspondence and requests for materials should be addressed to U.R. (Email: ruether@uni-duesseldorf.de) or to J.C.B. (Email: jens.bruening@uni-koeln.de).

Abstract

Several independent, genome-wide association studies have identified a strong correlation between body mass index and polymorphisms in the human FTO gene^{1, 2, 3, 4}. Common variants in the first intron define a risk allele predisposing to obesity, with homozygotes for the risk allele weighing approximately 3 kilograms more than homozygotes for the low risk allele¹. Nevertheless, the functional role of FTO in energy homeostasis remains elusive. Here we show that the loss of Fto in mice leads to postnatal growth retardation and a significant reduction in adipose tissue and lean body mass. The leanness of Fto-deficient mice develops as a consequence of increased energy expenditure and systemic sympathetic activation, despite decreased spontaneous locomotor activity and relative hyperphagia. Taken together, these experiments provide, to our knowledge, the first direct demonstration that Fto is functionally involved in energy homeostasis by the control of energy expenditure.

MORE ARTICLES LIKE THIS

These links to content published by NPG are automatically generated.