SHU 9119

Animal experiment:

Rats: SHU9119 is prepared in saline. SHU9119 is infused i.c.v. at a concentration of 24 nM and MTII at a concentration of 1 nM per day for 2 or 7 days. To differentiate between SHU9119 effects per se from those related to increased food intake, we prevent overeating in a group of SHU9119-treated rats by pair-feeding, so that they are given the same amount of food as consumed by a control group (SHU9119-pf). The pair-feeding regimen consists in giving one-third of the daily food amount in the morning and the remaining two-thirds just before onset of darkness. Thus, most of the experiments include 5 groups of animals: an ad libitum–fed control group infused with i.c.v. saline; 2 i.c.v. SHU9119-infused groups: SHU9119–ad lib and SHU9119-pf; an MTII-infused group; and a saline-pf group[2]. Mice: SHU9119 is prepared in artificial cerebrospinal fluid. After 4 weeks of run-in diet, mice are randomized into groups that received icv administration of artificial cerebrospinal fluid (vehicle) or SHU9119 (5 nmol/day) in vehicle during 14-17 days. The effect of SHU9119 on BAT activity independent of food intake is also investigated by using an additional SHU9119-treated group that is pair-fed (SHU9119-pf) to the vehicle-treated group. To achieve pair-feeding, food intake of the ad libitum-fed mice is monitored daily, and pair-fed mice receive surgery 1 day behind the control mice. The pair-feeding regimen consisted of giving the mice the average daily consumed food amount by the control mice, just before onset of darkness[3].

References:

[1]. Grieco P, et al. Further structure-activity studies of lactam derivatives of MT-II and SHU-9119: their activity and selectivity at human melanocortin receptors 3, 4, and 5. Peptides. 2007 Jun;28(6):1191-6.
[2]. Nogueiras R, et al. The central melanocortin system directly controls peripheral lipid metabolism. J Clin Invest. 2007 Nov;117(11):3475-88.
[3]. Kooijman S, et al. Inhibition of the central melanocortin system decreases brown adipose tissue activity. J Lipid Res. 2014 Oct;55(10):2022-32.