It has recently been suggested that gut-derived PYY3-36 may be involved in the central mediation of post-prandial satiety signals. We have examined the acute effects of peripherally administered PYY3-36 on food intake and hypothalamic gene expression of neuropeptides in mice. A single intraperitoneal injection Of PYY3-36 to mice that had been fasted for 24 h resulted in a highly significant reduction in food intake at 6 and 24 h post-injection but not at 48 h. However, in freely fed mice, food intake was unaltered by PYY3-36 administration. In the arcuate nucleus POMC mRNA expression was significantly elevated at 6 h and remained elevated at 24 h following PYY3-36 injection. By contrast NPY mRNA expression in the arcuate nucleus was suppressed at 6 h but not at 24 h post-injection. In the lateral hypothalamus there were no differences in MCH mRNA expression at either time point. In conclusion, peripherally administered PYY3-36 has a suppressive effect on food intake that is more prominent in recently fasted mice and lasts up to 24 h. This is associated with a short-lived suppression of NPY mRNA, a longer lasting increase in POMC mRNA but no change in MCH mRNA expression. (C) 2003 Elsevier Inc. All rights reserved.