|
PLoS One
2010
; 5
( 3
): e9468
Loss of the actin remodeler Eps8 causes intestinal defects and improved metabolic status in mice.
| Tocchetti
A
, Soppo
CB
, Zani
F
, Bianchi
F
, Gagliani
MC
, Pozzi
B
, Rozman
J
, Elvert
R
, Ehrhardt
N
, Rathkolb
B
, Moerth
C
, Horsch
M
, Fuchs
H
, Gailus-Durner
V
, Beckers
J
, Klingenspor
M
, Wolf
E
, Hrabé de Angelis
M
, Scanziani
E
, Tacchetti
C
, Scita
G
, Di Fiore
PP
, Offenhäuser
N
| Fondazione Instituto FIRC di Oncologia Molecolare, Milan, Italy.
|
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.
PMID: 20209148 [PubMed - in process] Click HERE for the full article |
