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OBJECTIVE: Neurons in the area postremaanucleus of the solitary tract (APaNTS) region mediate amylin's anorectic effect elicited by a single intraperitoneal (i.p.) injection of a low dose (5 mgakg). Here, we tested if a sustained elevation in amylin levels which was achieved by chronic amylin infusion reduces food intake by acting in the APaNTS region or, possibly, at other brain sites. Further, we tested the role of the APaNTS region in mediating the anorectic effects of high doses of amylin and its receptor agonist salmon calcitonin (sCT) after an acute single injection. DESIGN: Amylin (2 mgakgah) was chronically infused i.p. by osmotic minipumps in APaNTS-lesioned (AP-X) or sham-lesioned (SHAM) rats. For the acute experiments, amylin or sCT was injected i.p. at doses of 0.5 (only sCT), 5 or 50 mgakg. Food intake was measured by a computerized system. Body weight was assessed by manually weighing the rats. RESULTS: Amylin signi®cantly reduced cumulative food intake for about 7 days in SHAM but not in AP-X rats. Amylin's effect in SHAM rats was mainly due to a reduction of the size of nocturnal meals (eg average meal size during the ®rst four dark phases; SHAM, NaCl 4.1 AE 0.6 vs amylin 2.6 AE 0.4 g; n 6, P`0.05; AP-X, 2.6 AE 0.3 vs 3.7 AE 0.3) while light phase food intake was unaffected. Body weight gain over the whole 14 day infusion period was reduced by amylin in SHAM (NaCl 61 AE 6 vs amylin 46 AE 4 g; P`0.05) but not in AP-X rats (54 AE 4 vs 62 AE 4). After single injection, the anorectic effect of high doses of amylin and sCT (50 mgakg) was attenuated, but not abolished, in AP-X rats. CONCLUSION: We conclude that, under our experimental conditions, neurons in the APaNTS region are necessary for chronically elevated peripheral amylin to reduce food intake in rats. High doses of amylin, however, may be able to overrun these receptors and reduce feeding by acting at other brain sites.

The role of fatty acid oxidation in the control of food intake was studied using mercaptoacetate (MA), an inhibitor of fatty acid oxidation. Food intake, plasma free fatty acids (FFA) and ketone bodies, and blood glucose were measured. Rats were fed either a low-fat (LF, 3.33% fat) or a medium-fat (MF, 18% fat) diet. At the onset of the dark phase of the lighting cycle, MA did not affect food intake in LF rats but increased it 74% in MF rats in comparison to control. Four hours after the injection the effect of MA on food intake disappeared. In the middle of the bright phase of the lighting cycle, MA increased food intake in MF rats approximately 120% up to 6 h postinjection. After MA, plasma FFA concentration was elevated, and plasma 3-hydroxybutyrate concentration was lowered, indicating that fatty acid oxidation had been successfully reduced. MA did not affect blood glucose. These results indicate fatty acid oxidation is involved in the control of food intake, at least when the dietary fat level is relatively high.

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