The molecule known as PPARgamma is required for the development of fat cells and is the target of antidiabetic drugs known as thiazolidinediones (TZDs). In a study appearing online in advance of publication in the June print issue of the Journal of Clinical Investigation, Andrea Hevener and colleagues from UCSD report the unexpected finding that inactivation of PPARgamma in macrophages resulted in the development of insulin resistance in the livers of lean mice fed a normal diet, as well as impaired insulin signaling in fatty tissue, liver, and muscle. The authors went on to show that insulin resistance was even further impaired in these animals when they were fed a high-fat diet and the animals were only partially responsive to treatment with TZDs. The study reveals the essential role for PPARgamma in macrophages for the maintenance of insulin action in the whole body as well as in mediating the antidiabetic effects of TZDs. TITLE: Macrophage PPARgamma is required for normal skeletal muscle and hepatic insulin sensitivity and full antidiabetic effects of thiazolidinediones AUTHOR CONTACT: Andrea Hevener University of California, Los Angeles, Los Angeles, California, USA. Jerrold M. Olefsky or Christopher K. Glass University of California, San Diego, California, USA. Mercedes Ricote Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain. ### JCI table of contents: May 24, 2007 Contact: Brooke Grindlinger