Chronic Application of MTII in a Rat Model of Obesity Results in Sustained Weight Loss

Objective: To examine the effects of a cafeteria diet and a chronic treatment with melanocortin agonist (MTII) on mature weight-stable female rats. Research Methods and Procedures: Ex-breeder Chbb:Thom rats (350 to 400 g) were divided into two groups: highly palatable food (HPF) and normal rat chow (RC). Both groups had ab libitum access to rat chow. The HPF group had access to chocolate bars, cookies, cheese, and nuts (～20 g/d). After 21 days, the rats in each group were then divided into control and treated groups. Mini-pumps delivering saline or MTII (1 mg/kg per day) for minimally 28 days were implanted. Oxygen consumption was measured for 17 days in a second group of rats implanted with mini-pumps containing MTII (1 mg/kg per day) or saline. Results: HPF rats ate less (<50%) rat chow than RC rats. After 20 days, the HPF group had reached a plateau and weighed significantly more (p < 0.005) than the RC group (411.7 ± 9.3 g; n = 17 vs. 365.1 ± 9.4 g; n = 16). HPF rats and RC rats receiving MTII reduced their pellet intake and body weight in the initial 2 weeks of treatment (day 14, RC-saline: ?1.6 ± 1.8 g; RC-MTII, ?22.5 ± 3.7 g; HPF-saline, ?7.1 ± 1.7 g; HPF-MTII, ?30.7 ± 4.8 g). Subsequently, pellet intake returned to pre-implantation values, although body weights remained reduced in both HPF and RC groups. Oxygen consumption was increased in rats treated with MTII. Discussion: This suggests that MTII initially reduced body weight by limiting food intake; however, maintenance of weight is most likely due to increased energy expenditure under conditions of normal and highly palatable diets in mature animals.