In a study that appears online on August 9 in advance of publication in the September print issue of the Journal of Clinical Investigation, Clay Semenkovich and colleagues from Washington University School of Medicine, St. Louis, show that mice lacking a protein known as FAS in beta-islet cells in the pancreas and in the region of the brain known as the hypothalamus are lean because they eat less and move around more than normal mice. These effects on behavior were associated with decreased signaling in the hypothalamus through a protein known as PPAR-alpha. Administration of a PPAR-alpha agonist into the hypothalamus increased the amount mice lacking FAS specifically in the beta-islet cells and in the hypothalamus ate but did not increase the amount normal mice ate. This study therefore identifies FAS-mediated activation of PPAR-alpha as a molecular pathway controlling feeding behavior in mice.-Journal of Clinical Investigation
