Amylin is a 37-amino acid peptide hormone that is co-secreted with insulin
by pancreatic beta cells in response to feeding. We recently reported that
amylin potently reduces food intake, body weight, and adiposity when delive
red into the 3(rd) cerebral ventricle (i3vt) of rats. We have now infused i
3vt a specific antagonist (AC187) to ascertain the physiological relevance
of central amylin in the control of energy balance. After establishing the
ability of i3vt AC187 to block the anorexic effect of i3vt amylin, we perfo
rmed an experiment to examine the impact of acute inhibition of central amy
lin signaling on feeding. Separate groups (n = 7/group) of ad lib-fed male
Long Evans rats were given one bolus i3vt infusion of synthetic cerebrospin
al fluid vehicle (CSF) or AC187 (250 or 1000 pmol). Acute infusion of AC187
tended to increase 1-h food intake and significantly elevated 4-h intake.
Both the 250 and 1000 pmol doses produced significant increases as compared
to CSF. In another experiment designed to tonically inhibit central amylin
signaling over an extended period, two other groups of rats (n = 6/group)
received continuous i3vt infusion of CSF or 100 pmol/h AC187 over 14 days v
ia implantable osmotic pumps. Rats receiving AC187 ate significantly more f
ood over the 14-day infusion period relative to controls (CSF = 322 +/- 6 g
, AC187 = 360 +/- 12 g). Although body weight was not significantly affecte
d, body fat was increased by about 30% in the AC187 rats, with no differenc
e in lean tissue between the groups. Additionally, although fasting plasma
glucose did not differ between the CSF and AC187 groups after 14 days of in
fusion, plasma insulin was significantly elevated in the AC187 rats. In sum
mary, the present results document significant increases of food intake and
body adiposity resulting from inhibition of central amylin signaling. They
are consistent with our hypothesis that CNS actions of endogenous amylin c
ontribute to the long-term regulation of energy balance.