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Loss of the Actin Remodeler Eps8 Causes Intestinal Defects and Improved Metabolic Status in Mice

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...

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Detalles Bibliográficos
Autores principales: Tocchetti, Arianna, Ekalle Soppo, Charlotte Blanche, 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, de Angelis, Martin Hrabé, Scanziani, Eugenio, Tacchetti, Carlo, Scita, Giorgio, Di Fiore, Pier Paolo, Offenhäuser, Nina
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2830459/
https://www.ncbi.nlm.nih.gov/pubmed/20209148
http://dx.doi.org/10.1371/journal.pone.0009468
Descripción
Sumario: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.