PMID- 17981116
OWN - NLM
STAT- MEDLINE
DCOM- 20071206
LR  - 20131121
IS  - 0092-8674 (Print)
IS  - 0092-8674 (Linking)
VI  - 131
IP  - 3
DP  - 2007 Nov 2
TI  - Targeted deletion of AIF decreases mitochondrial oxidative phosphorylation and 
      protects from obesity and diabetes.
PG  - 476-91
AB  - Type-2 diabetes results from the development of insulin resistance and a 
      concomitant impairment of insulin secretion. Recent studies place altered 
      mitochondrial oxidative phosphorylation (OxPhos) as an underlying genetic element 
      of insulin resistance. However, the causative or compensatory nature of these 
      OxPhos changes has yet to be proven. Here, we show that muscle- and 
      liver-specific AIF ablation in mice initiates a pattern of OxPhos deficiency 
      closely mimicking that of human insulin resistance, and contrary to current 
      expectations, results in increased glucose tolerance, reduced fat mass, and 
      increased insulin sensitivity. These results are maintained upon high-fat feeding 
      and in both genetic mosaic and ubiquitous OxPhos-deficient mutants. Importantly, 
      the effects of AIF on glucose metabolism are acutely inducible and reversible. 
      These findings establish that tissue-specific as well as global OxPhos defects in 
      mice can counteract the development of insulin resistance, diabetes, and obesity.
FAU - Pospisilik, J Andrew
AU  - Pospisilik JA
AD  - Institute of Molecular Biotechnology of the Austrian Academy of Science, Dr 
      Bohrgasse 3, 1030, Vienna, Austria.
FAU - Knauf, Claude
AU  - Knauf C
FAU - Joza, Nicholas
AU  - Joza N
FAU - Benit, Paule
AU  - Benit P
FAU - Orthofer, Michael
AU  - Orthofer M
FAU - Cani, Patrice D
AU  - Cani PD
FAU - Ebersberger, Ingo
AU  - Ebersberger I
FAU - Nakashima, Tomoki
AU  - Nakashima T
FAU - Sarao, Renu
AU  - Sarao R
FAU - Neely, Gregory
AU  - Neely G
FAU - Esterbauer, Harald
AU  - Esterbauer H
FAU - Kozlov, Andrey
AU  - Kozlov A
FAU - Kahn, C Ronald
AU  - Kahn CR
FAU - Kroemer, Guido
AU  - Kroemer G
FAU - Rustin, Pierre
AU  - Rustin P
FAU - Burcelin, Remy
AU  - Burcelin R
FAU - Penninger, Josef M
AU  - Penninger JM
LA  - eng
SI  - GEO/GSE8905
GR  - DK31036/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cell
JT  - Cell
JID - 0413066
RN  - 0 (Apoptosis Inducing Factor)
RN  - 0 (Insulin)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
CIN - Cell. 2007 Nov 2;131(3):448-50. PMID: 17981112
MH  - Animals
MH  - Apoptosis Inducing Factor/*deficiency/genetics
MH  - Cell Respiration/drug effects
MH  - Diabetes Mellitus/genetics/metabolism/*prevention & control
MH  - Diet/adverse effects
MH  - *Gene Deletion
MH  - *Gene Targeting
MH  - Glucose/metabolism
MH  - Insulin/pharmacology
MH  - Liver/cytology/drug effects/metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Mitochondria/drug effects/*metabolism
MH  - Mosaicism/drug effects
MH  - Muscles/cytology/drug effects/metabolism
MH  - Obesity/genetics/metabolism/*prevention & control
MH  - Organ Specificity/drug effects
MH  - *Oxidative Phosphorylation/drug effects
MH  - Phenotype
MH  - Substrate Specificity/drug effects
EDAT- 2007/11/06 09:00
MHDA- 2007/12/07 09:00
CRDT- 2007/11/06 09:00
PHST- 2007/04/06 00:00 [received]
PHST- 2007/07/02 00:00 [revised]
PHST- 2007/08/29 00:00 [accepted]
PHST- 2007/11/06 09:00 [pubmed]
PHST- 2007/12/07 09:00 [medline]
PHST- 2007/11/06 09:00 [entrez]
AID - S0092-8674(07)01197-X [pii]
AID - 10.1016/j.cell.2007.08.047 [doi]
PST - ppublish
SO  - Cell. 2007 Nov 2;131(3):476-91. doi: 10.1016/j.cell.2007.08.047.