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 (2010): Loss of the actin remodeler Eps8 causes intestinal defects and improved metabolic status in mice.
In: PLOS ONE 5(3), e9468




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. 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. 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.