Faculté des sciences

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

In: PLoS ONE, 2010, vol. 5, no. 3, p. e9468

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... Plus

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    Summary
    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.