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Loss of the actin remodeler Eps8 causes calorie restriction and improved metabolic status in mice

ABSTRACT: 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 bodyweight, partial resistance to age- or diet-induced obesity, and overall improved metabolic status. We present evidence that these phenotypes, which are associated to increased lifespan in the Eps8 null mice, are due to caloric restriction. This, in turn, is caused by reduced intestinal fat absorption, due to altered morphogenesis of microvilli in intestinal enterocytes. In the nematode, genetic removal of Eps8, causes a microvillar phenotype, indistinguishable from that observed in mice, which leads to early larval lethality. By exploiting the nematode model system, we demonstrate here that the actin bundling activity of Eps8 is indispensable for viability and proper intestinal morphogenesis. This result links a precise molecular function of Eps8 to proper microvillar morphogenesis, and therefore to the phenotype of Eps8-null mice. Our results implicate actin dynamics in individual variations in bodyweight, metabolic status and longevity.

ORGANISM(S): Mus musculus

PROVIDER: GSE14454 | GEO | 2010/03/09

SECONDARY ACCESSION(S): PRJNA111565

REPOSITORIES: GEO

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