THE ARCUATE NUCLEUS AS A PRIMARY SITE OF SATIETY EFFECT OF LEPTIN IN RATS

The obese (ob) gene encodes a fat cell-derived circulating satiety fac tor (leptin) that is involved in the regulation of energy homeostasis. In the present study, we examined effects of i.c.v. injection of reco mbinant human leptin on food intake and body weight gain in rats. We a lso studied effects of direct microinjections of leptin into the arcua te nucleus (Arc), ventromedial hypothalamus (VMH), and lateral hypotha lamus (LH). A single i.c.v. injection of recombinant human leptin (0.2 5-2.0 mu g/rat) reduced significantly and dose-dependently food intake and body weight gain in rats. Microinjections (0.125-0.5 mu g/site) i nto the bilateral Arc, VMH, and LH caused dose-related decreases in fo od intake and body weight gain as compared with vehicle-treated groups with a rank order of potency; Arc > VMH = LH. The present study provi des the first direct evidence that the Arc is a primary site of satiet y effect of leptin. (C) 1997 Elsevier Science Ireland Ltd.