Loss of the actin remodeler Eps8 causes intestinal defects and improved metabolic status in mice

Tocchetti, Arianna; Soppo, Charlotte Blanche Ekalle; Zani, Fabio; Bianchi, Fabrizio; Gagliani, Maria Cristina; Pozzi, Benedetta; Rozman, Jan; Elvert, Ralf; Ehrhardt, Nicole; Rathkolb, Birgit; Moerth, Corinna; Horsch, Marion; Fuchs, Helmut; Gailus-Durner, Valérie; Beckers, Johannes; Klingenspor, Martin; Wolf, Eckhard; Hrabé de Angelis, Martin; Scanziani, Eugenio; Tacchetti, Carlo; Scita, Giorgio; Di Fiore, Pier Paolo; Offenhäuser, Nina

doi:10.1371/journal.pone.0009468

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Journal article

Loss of the actin remodeler Eps8 causes intestinal defects and improved metabolic status in mice

Tocchetti, Arianna Fondazione Instituto FIRC di Oncologia Molecolare, Milan, Italy - KtedoGen srl, Milan, Italy
Soppo, Charlotte Blanche Ekalle Fondazione Instituto FIRC di Oncologia Molecolare, Milan, Italy
Zani, Fabio Fondazione Instituto FIRC di Oncologia Molecolare, Milan, Italy - Department of Physiology, University of Fribourg, Switzerland
Bianchi, Fabrizio Fondazione Instituto FIRC di Oncologia Molecolare, Milan, Italy - Dipartimento di Medicina, Chirurgia ed Odontoiatria, Universita' degli Studi di Milano, Italy
Gagliani, Maria Cristina Fondazione Instituto FIRC di Oncologia Molecolare, Milan, Italy - Department of Experimental Medicine, University of Genoa, Italy
Pozzi, Benedetta Fondazione Instituto FIRC di Oncologia Molecolare, Milan, Italy
Rozman, Jan German Mouse Clinic, Helmholtz Zentrum München, Munich/Neuherberg, Germany - Molecular Nutritional Medicine, Technische Universität München, Freising-Weihenstephan, Germany
Elvert, Ralf German Mouse Clinic, Helmholtz Zentrum München, Munich/Neuherberg, Germany - Sanofi-Aventis GmbH, Frankfurt am Main, Germany
Ehrhardt, Nicole German Mouse Clinic, Helmholtz Zentrum München, Munich/Neuherberg, Germany - Department of Medical Genetics, Cedars-Sinai Medical Center, Los Angeles, USA
Rathkolb, Birgit German Mouse Clinic, Helmholtz Zentrum München, Munich/Neuherberg, Germany - Institute of Molecular Animal Breeding and Biotechnology, Ludwig Maximilians Universität München, Germany
Moerth, Corinna German Mouse Clinic, Helmholtz Zentrum München, Munich/Neuherberg, Germany - Institute of Molecular Animal Breeding and Biotechnology, Ludwig Maximilians Universität München, Germany - Animal Facility, Max Planck Institute of Biochemistry, Martinsried, Germany
Horsch, Marion German Mouse Clinic, Helmholtz Zentrum München, Munich/Neuherberg, Germany
Fuchs, Helmut German Mouse Clinic, Helmholtz Zentrum München, Munich/Neuherberg, Germany
Gailus-Durner, Valérie German Mouse Clinic, Helmholtz Zentrum München, Munich/Neuherberg, Germany
Beckers, Johannes German Mouse Clinic, Helmholtz Zentrum München, Munich/Neuherberg, Germany - Lehrstuhl für Experimentelle Genetik, Technische Universität München, Germany
Klingenspor, Martin Molecular Nutritional Medicine, Technische Universität München, Freising-Weihenstephan, Germany
Wolf, Eckhard Institute of Molecular Animal Breeding and Biotechnology, Ludwig Maximilians Universität München, Germany
Hrabé de Angelis, Martin German Mouse Clinic, Helmholtz Zentrum München, Munich/Neuherberg, Germany - Lehrstuhl für Experimentelle Genetik, Technische Universität München, Germany
Scanziani, Eugenio Facoltà di Medicina Veterinaria, Università degli Studi di Milano, Italy
Tacchetti, Carlo Fondazione Instituto FIRC di Oncologia Molecolare, Milan, Italy - Department of Experimental Medicine, University of Genoa, Italy
Scita, Giorgio Fondazione Instituto FIRC di Oncologia Molecolare, Milan, Italy - Dipartimento di Medicina, Chirurgia ed Odontoiatria, Universita' degli Studi di Milano, Italy
Di Fiore, Pier Paolo Fondazione Instituto FIRC di Oncologia Molecolare, Milan, Italy - Dipartimento di Medicina, Chirurgia ed Odontoiatria, Universita' degli Studi di Milano, Italy - Istituto Europeo di Oncologia, Milan, Italy
Offenhäuser, Nina Fondazione Instituto FIRC di Oncologia Molecolare, Milan, Italy

02.03.2010

Published in:

PLoS ONE. - 2010, vol. 5, no. 3, p. e9468

English Background: In a variety of organisms, including mammals, caloric restriction improves metabolic status and lowers the incidence of chronic-degenerative diseases, ultimately leading to increased lifespan. Methodology/Principal Findings: Here we show that knockout mice for Eps8, a regulator of actin dynamics, display reduced body weight, partial resistance to age- or diet-induced obesity, and overall improved metabolic status. Alteration in the liver gene expression profile, in behavior and metabolism point to a calorie restriction-like phenotype in Eps8 knockout mice. Additionally, and consistent with a calorie restricted metabolism, Eps8 knockout mice show increased lifespan. The metabolic alterations in Eps8 knockout mice correlated with a significant reduction in intestinal fat absorption presumably caused by a 25% reduction in intestinal microvilli length. Conclusions/Significance: Our findings implicate actin dynamics as a novel variable in the determination of longevity. Additionally, our observations suggest that subtle differences in energy balance can, over time, significantly affect bodyweight and metabolic status in mice.

Faculty

Faculté des sciences et de médecine

Department

Département de Médecine

Language