Effects of a novel MC4R agonist on maintenance of reduced body weight in diet-induced obese mice.
Obesity (Silver Spring)
; 22(5): 1287-95, 2014 May.
Article
en En
| MEDLINE
| ID: mdl-24318934
OBJECTIVE: The physiology of the weight-reduced (WR) state suggests that pharmacologic agents affecting energy homeostasis may have greater efficacy in WR individuals. Our aim was to establish a protocol that allows for evaluation of efficacy of weight maintenance agents and to assess the effectiveness of AZD2820, a novel melanocortin 4 receptor (MC4R) agonist in such a paradigm. METHODS: MC4R agonist was administered in stratified doses to mice who were either fed high-fat diet ad libitum (AL) throughout the study; or stabilized at a 20% reduced body weight (BW), administered the drug for 4 weeks, and thereafter released from caloric restriction while continuing to receive the drug (WR). RESULTS: After release of WR mice to AL feeding, the high-dose group (53.4 nmol/day) regained 12.4% less BW than their vehicle-treated controls since the beginning of drug treatment. In WR mice, 10.8 nmol/day of the agonist was sufficient to maintain these animals at 95.1% of initial BW versus 53.4 nmol/day required to maintain the BW of AL animals (94.5%). CONCLUSIONS: In the WR state, the MC4R agonist was comparably efficacious to a five-fold higher dose in the AL state. This protocol provides a model for evaluating the mechanisms and quantitative efficacy of weight-maintenance strategies and agents.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Peso Corporal
/
Receptor de Melanocortina Tipo 4
/
Obesidad
Tipo de estudio:
Guideline
Límite:
Animals
Idioma:
En
Revista:
Obesity (Silver Spring)
Asunto de la revista:
CIENCIAS DA NUTRICAO
/
FISIOLOGIA
/
METABOLISMO
Año:
2014
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Estados Unidos