1: Cell. 2007 Nov 2;131(3):476-91.

Targeted Deletion of AIF Decreases Mitochondrial Oxidative Phosphorylation and
Protects from Obesity and Diabetes.

Pospisilik JA, Knauf C, Joza N, Benit P, Orthofer M, Cani PD, Ebersberger I,
Nakashima T, Sarao R, Neely G, Esterbauer H, Kozlov A, Kahn CR, Kroemer G, Rustin
P, Burcelin R, Penninger JM.

Institute of Molecular Biotechnology of the Austrian Academy of Science, Dr.
Bohrgasse 3, 1030 Vienna, Austria.

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.

PMID: 17981116 [PubMed - in process]

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