부산대학교 도서관

Background/Objectives Cholecystokinin (CCK) is a regulator of appetite and energy intake in man. The aim of this study was to determine the effect of NN9056, a long-acting CCK-1 receptor-selective CCK analogue, on food intake and body weight (BW) in obese Göttingen Minipigs. Subjects/Methods Tolerability of NN9056 and acute effects on food intake, pancreas histology, amylase and lipase levels were assessed in lean domestic pigs in doses up to 100 nmol/kg (n = 3-4). Subsequently, obese Göttingen Minipigs were treated subcutaneously (s.c.) once daily for 13 weeks with vehicle, NN9056 low dose (regulated from 5 to 2 nmol/kg) or NN9056 high dose (10 nmol/kg) (n = 7-8). Food intake was measured daily and BW twice weekly. At the end of the treatment period, an intravenous glucose tolerance test (IVGTT) and a 24-h exposure profile was obtained. Data are mean [plus or minus] SD. Results The acute studies in domestic pigs showed significant and dose-dependent effect of NN9056 on food intake, acceptable tolerability and no histopathological signs of pancreatitis. Sub-chronic treatment in obese Göttingen Minipigs was also well tolerated and accumulated food intake was significantly lower in both treated groups compared to vehicle, with no significant difference between the dose levels of NN9056 (41.8 [plus or minus] 12.6, 51.5 [plus or minus] 13.8 and 86.5 [plus or minus] 19.5 kg in high-dose, low-dose and vehicle groups, respectively, p = 0.012 and p < 0.0001 for low and high dose vs. vehicle, respectively). Accordingly, there was a weight loss in both treated groups vs. a weight gain in the vehicle group (-7.2 [plus or minus] 4.6%, -2.3 [plus or minus] 3.2% and 12.3 [plus or minus] 3.9% in the high-dose, low-dose and vehicle groups, respectively, p < 0.0001 for both vs. vehicle). IVGTT data were not significantly different between groups. Conclusion NN9056, a long-acting CCK-1 receptor-selective CCK analogue, significantly reduced food intake and BW in obese Göttingen Minipigs after once daily s.c. dosing for 13 weeks.
Author(s): Berit Ø. Christoffersen [sup.1], Rikke Bjerring Skyggebjerg [sup.1], Anne Bugge [sup.1], Rikke Kaae Kirk [sup.1], Bill Vestergaard [sup.1], Henriette Kold Uldam [sup.2], Johannes Josef Fels [sup.2], Charles Pyke [sup.1], [...]