Regulation of OPG by osteoblastic Hdac3 to control hepatic inflammation and systemic insulin sensitivity

We are studying a novel role for osteoblastic expression of histone deacetylase 3 (Hdac3) in the regulation of systemic energy metabolism. Mice that do not express Hdac3 in the skeleton are more sensitive to insulin and are protected against the development of type 2 diabetes. Our studies suggest that this effect is mediated through the up-regulation of anti-inflammatory osteoprotegerin (OPG) which helps prevent the onset of insulin resistance in the liver. This work will have collective impact because its studies will identify therapeutic targets for millions of Americans suffering from obesity and metabolic disorders.