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] Related Links Reduced expression of nuclear-encoded genes involved in mitochondrial oxidative metabolism in skeletal muscle of insulin-resistant women with polycystic ovary syndrome. [Diabetes. 2007] PMID:17563058 Mitochondrial oxidative function and type 2 diabetes. [Appl Physiol Nutr Metab. 2006] PMID:17213881 Unraveling the temporal pattern of diet-induced insulin resistance in individual organs and cardiac dysfunction in C57BL/6 mice. [Diabetes. 2005] PMID:16306372 Disordered fat storage and mobilization in the pathogenesis of insulin resistance and type 2 diabetes. [Endocr Rev. 2002] PMID:11943743 Chronological approach of diet-induced alterations in muscle mitochondrial functions in rats. [Obesity (Silver Spring). 2007] PMID:17228031