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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
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    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
  • English
Classification
Biological sciences
License
License undefined
Identifiers
Persistent URL
https://folia.unifr.ch/unifr/documents/301609
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