Physiological role of cholecystokinin B/gastrin receptor in leptin secretion

In the present study, we investigated whether cholecystokinin (CCK) or its structurally related peptide gastrin participates in long term regulation o f adipocyte leptin secretion. The levels of circulating leptin observed aft er 2 and 6 h of refeeding in 18-h fast rats were significantly lowered by i njection of the specific gastrin/CCK-B receptor antagonist YM022 at doses t hat did not affect feeding behavior. Moreover, in normally fed animals, cir culating leptin was markedly decreased by chronic injection of YM022 (from 4 +/- 0.6 to 2.1 +/- 0.5 ng/ml). Consistent with these observations, YM022 treatment decreased leptin messenger RNA (mRNA) levels and increased the le ptin content in rat epididymal fat tissue. Rat adipocytes exclusively conta in gastrin/CCK-B receptor mRNA, but not CCK-A receptor mRNA. Furthermore, a dipocyte membranes bound [I-125]CCK-8 in a saturable manner, with kinetics consistent with a single class of high affinity sites with a K-d of 0.2 nM. These data argue for a physiological role for the CCK-B/gastrin receptor i n adipocyte leptin regulation. We therefore propose that gastrin is involve d in long term regulation of leptin expression and secretion in rat fat tis sues through activation of an adipocyte gastrin/CCK-B receptor.