title: Loss of the actin remodeler Eps8 causes intestinal defects and improved metabolic status in mice.
abstract: 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.
  
  
  RESULTS
  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
  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.
authors.affiliation: Fondazione Instituto FIRC di Oncologia Molecolare, Milan, Italy.
authors.forename: Arianna
authors.initials: A
authors.lastname: Tocchetti
authors.forename: Charlotte Blanche Ekalle
authors.initials: CB
authors.lastname: Soppo
authors.forename: Fabio
authors.initials: F
authors.lastname: Zani
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Bianchi
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Gagliani
authors.forename: Benedetta
authors.initials: B
authors.lastname: Pozzi
authors.forename: Jan
authors.initials: J
authors.lastname: Rozman
authors.forename: Ralf
authors.initials: R
authors.lastname: Elvert
authors.forename: Nicole
authors.initials: N
authors.lastname: Ehrhardt
authors.forename: Birgit
authors.initials: B
authors.lastname: Rathkolb
authors.forename: Corinna
authors.initials: C
authors.lastname: Moerth
authors.forename: Marion
authors.initials: M
authors.lastname: Horsch
authors.forename: Helmut
authors.initials: H
authors.lastname: Fuchs
authors.forename: Valérie
authors.initials: V
authors.lastname: Gailus-Durner
authors.forename: Johannes
authors.initials: J
authors.lastname: Beckers
authors.forename: Martin
authors.initials: M
authors.lastname: Klingenspor
authors.forename: Eckhard
authors.initials: E
authors.lastname: Wolf
authors.forename: Martin
authors.initials: M
authors.lastname: Hrabé de Angelis
authors.forename: Eugenio
authors.initials: E
authors.lastname: Scanziani
authors.forename: Carlo
authors.initials: C
authors.lastname: Tacchetti
authors.forename: Giorgio
authors.initials: G
authors.lastname: Scita
authors.forename: Pier Paolo
authors.initials: PP
authors.lastname: Di Fiore
authors.forename: Nina
authors.initials: N
authors.lastname: Offenhäuser
mesh_terms: D041721:3T3-L1 Cells; D000199:Actins / Q000378:metabolism*; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001835:Body Weight; D018938:Caco-2 Cells; D031204:Caloric Restriction; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000502:physiology*; D004734:Energy Metabolism; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008871:Microvilli / Q000378:metabolism
chemical_list: D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; C083430:Eps8 protein, mouse