Loss of the actin remodeler Eps8 causes intestinal defects and improved metabolic status in mice.
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.
Tocchetti
Arianna
A
Fondazione Instituto FIRC di Oncologia Molecolare, Milan, Italy.
Soppo
Charlotte Blanche Ekalle
CB
Zani
Fabio
F
Bianchi
Fabrizio
F
Gagliani
Maria Cristina
MC
Pozzi
Benedetta
B
Rozman
Jan
J
Elvert
Ralf
R
Ehrhardt
Nicole
N
Rathkolb
Birgit
B
Moerth
Corinna
C
Horsch
Marion
M
Fuchs
Helmut
H
Gailus-Durner
Valérie
V
Beckers
Johannes
J
Klingenspor
Martin
M
Wolf
Eckhard
E
Hrabé de Angelis
Martin
M
Scanziani
Eugenio
E
Tacchetti
Carlo
C
Scita
Giorgio
G
Di Fiore
Pier Paolo
PP
Offenhäuser
Nina
N
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
D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; C083430:Eps8 protein, mouse