1780-P: In High-Fat Diet-Induced Mice Skeletal Muscles, Iron Overload Plays a Critical Role in Leading Insulin Resistance

Aim/Hypotheses: Iron plays an important role in many physiological processes, including redox balance, inflammation, and mitochondrial respiratory metabolism. Abnormalities in iron metabolism lead to insulin resistance as well as diabetes. However, the abnormal mechanism of iron metabolism in the muscles of insulin resistance animal models is not precisely well known. Therefore, we investigated the molecular mechanism underlying iron dysregulation in high fat diet-induced C57BL/6J mice skeletal muscles. Methods: We measured intracellular iron content in skeletal muscle tissues and iron metabolism related protein levels, such as transferrin receptor1, heavy chain ferritin, light chain ferritin, DMT1, and ferroportin. To investigate the association between iron content and insulin resistance, we treated iron donor or chelator in an animal model and performed insulin tolerance tests and measurement of insulin signaling. Results: Interestingly, intracellular iron levels were increased in high fat diet-induced mice skeletal muscles. We also observed up-regulation of transferrin receptor 1 (TfR1), ferritin, but did not observe a change of DMT1 and ferroportin. Treatment with iron dextran, an iron donor, in C57BL/6J normal mice induced insulin resistance. However, treatment of desferrioxamine, an iron chelator, in high fat diet-induced insulin resistance mice recovered insulin resistance. Iron overload with iron dextran impaired insulin signaling in skeletal muscles, while iron chelation with desferrioxamine recovered high fat-induced dysregulated insulin signaling. Conclusions/interpretation: Therefore, we consider fine-tuning of skeletal muscle iron levels and highly suggest the use for preventing and/or treating insulin resistance and diabetes. Disclosure S. Choi: None. N. Lee: None. H. Moon: None. H. Kim: None. J. Jeon: None. Y. Kang: None. T. Kim: None. K. Lee: None.