31 Gillum, M. P. Zhang, D. Zhang, X. M. Erion, D. M. Jamison, R. A. Choi, C. Dong, J. Shanabrough, M. Duenas, H. R. Frederick, D. W. Hsiao, J. J. Horvath, T. L. Lo, C. M. Tso, P. Cline, G. W. Shulman, G. I. 2008 Cell 135 5 813-24 Nov 28 1097-4172 (Electronic) 19041747 Tandem Mass Spectrometry Rats Proto-Oncogene Proteins c-fos/metabolism Phosphatidylethanolamines/blood/*physiology Palmitic Acids/metabolism Obesity/metabolism Motor Activity Mice, Obese Mice Intestine, Small/metabolism Hypothalamus/metabolism Dietary Fats/metabolism Body Weight *Appetite Regulation Animals Obese Intestine Small/metabolism N-acylphosphatidylethanolamines (NAPEs) are a relatively abundant group of plasma lipids of unknown physiological significance. Here, we show that NAPEs are secreted into circulation from the small intestine in response to ingested fat and that systemic administration of the most abundant circulating NAPE, at physiologic doses, decreases food intake in rats without causing conditioned taste aversion. Furthermore, (14)C-radiolabeled NAPE enters the brain and is particularly concentrated in the hypothalamus, and intracerebroventricular infusions of nanomolar amounts of NAPE reduce food intake, collectively suggesting that its effects may be mediated through direct interactions with the central nervous system. Finally, chronic NAPE infusion results in a reduction of both food intake and body weight, suggesting that NAPE and long-acting NAPE analogs may be novel therapeutic targets for the treatment of obesity. P30 DK-45735/DK/NIDDK NIH HHS/United StatesR01 DK-40936/DK/NIDDK NIH HHS/United StatesU24 DK-76169/DK/NIDDK NIH HHS/United StatesHoward Hughes Medical Institute/United StatesJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov'tUnited States http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19041747