Neuropeptide Y (NPY) is a potent feeding stimulant acting at the level of the hypothalamus.
Amylin, a
peptide co-released with
insulin from pancreatic beta cells, inhibits feeding following peripheral or central administration. However, the mechanism by which
amylin exerts its
anorectic effect is controversial. This study investigated the acute effect of
amylin on food intake induced by NPY, and the effect of chronic
amylin administration on food intake and
body weight in male Sprague Dawley rats previously implanted with intracerebroventricular (icv)
cannulae. Rats received 1 nmol NPY, followed by
amylin (0.05, 0.1, 0.5 nmol) or 2 microl saline. Increasing doses of
amylin resulted in a dose-dependent inhibition of NPY-induced feeding by 31%, 74% and 99%, respectively (P < 0.05). To determine the chronic effects of i.c.v.
amylin administration on feeding, rats received 0.5 nmol
amylin or saline daily, 30 min before dark phase, over 6 days.
Amylin significantly reduced food intake at 1, 4, 16 and 24 hours; after 6 days,
amylin-treated rats showed a significant reduction in
body weight, having lost 17.3 +/- 6.1 g, while control animals gained 7.7 +/- 5.1 g (P < 0.05). Brain NPY concentrations were not elevated, despite the reduced food intake, suggesting
amylin may regulate NPY production or release. Thus,
amylin potently inhibits NPY-induced feeding and attenuates normal 24 hour food intake, leading to
weight loss.