PLoS ONE (Jan 2010)

Loss of the actin remodeler Eps8 causes intestinal defects and improved metabolic status in mice.

  • Arianna Tocchetti,
  • Charlotte Blanche Ekalle Soppo,
  • Fabio Zani,
  • Fabrizio Bianchi,
  • Maria Cristina Gagliani,
  • Benedetta Pozzi,
  • Jan Rozman,
  • Ralf Elvert,
  • Nicole Ehrhardt,
  • Birgit Rathkolb,
  • Corinna Moerth,
  • Marion Horsch,
  • Helmut Fuchs,
  • Valérie Gailus-Durner,
  • Johannes Beckers,
  • Martin Klingenspor,
  • Eckhard Wolf,
  • Martin Hrabé de Angelis,
  • Eugenio Scanziani,
  • Carlo Tacchetti,
  • Giorgio Scita,
  • Pier Paolo Di Fiore,
  • Nina Offenhäuser

DOI
https://doi.org/10.1371/journal.pone.0009468
Journal volume & issue
Vol. 5, no. 3
p. e9468

Abstract

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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.