Type 2 diabetes is characterized by insulin resistance and mitochondrial dysfunction in classical target tissues such as muscle, fat, and liver. Using a murine model of type 2 diabetes, we show that there is hypothalamic insulin resistance and mitochondrial dysfunction due to downregulation of the mitochondrial chaperone HSP60. HSP60 reduction in obese, diabetic mice was due to a lack of proper leptin signaling and was restored by leptin treatment. Knockdown of
André Kleinridders, Hans P.M.M. Lauritzen, Siegfried Ussar, Jane H. Christensen, Marcelo A. Mori, Peter Bross, C. Ronald Kahn
HSP60 reduction is associated with central insulin resistance.