Effects of Intracerebroventricular Infusion of MTII in Monosodium Glutamate(MSG)-obese Rats

Kwon, Oh Jin; Choi, Dong Weon; Huh, Jung Yoon; Bae, Jei Jun; Kim, Jin Hee; Park, Yoon Ki; Kim, Jong Yeon; Kim, Yong Woon

Abstract

BACKGROUND: Leptin, secreted by adipose tissue, is an afferent signal molecule that contributes to body fat homeostasis through regulation of both food intake and energy expenditure. These effects are mediated by activation of proopiomelanocortin(PO MC) producing neuron in the arcuate nucleus of hypothalamus where the leptin receptor is located. alpha-MSH cleaved from POMC activates melanocortin receptor in the paraventricular nucleus of hypothalamus. However, obese rodents respond poorly to pharmacological administration of exogenous leptin beacuse of leptin resistance. Bypassing the arcuate nucleus would be a possible mechanism for making leptin-like effect.
METHODS
In this study, to evaluate whether MTII, a melanocortin receptor 3/4 agonist, induces leptinlike effects and activates UCP1 and UCP3 in hypophagic and hypothermogenic obese model, food intake, body weight, oxygen consumption, fat mass, and expression of UCP1 of brown adipose tissue (BAT) and UCP3 of soleus after 1 week of intracerebroventricular(i.c.v.) infusion of MTII in monosodium glutamate(MSG) induced obese rats. MTII or artificial cerebrospinal fluid(aCSF) was infused into i.c.v. with osmotic minipump. MSG-obese rats were induced by neonatal injection of MSG.
RESULTS
Five-month old MSG rats were characterized by hypophagia, lower oxygen consumption, hyperleptinemia and obesity compared with agematched control rats. The infusion of MTII decreased the food intake, visceral fat and body weight in MSG-obese rats compared with aCSF infused rats. The oxygen consumption was increased by MTII treatment in MSG-obese rats compared with aCSF as well as pair-fed rats. BAT UCP1 mRNA expression was increased by MTII treatment compared with pair fed rats in MSG-obese rats as well as controls, which was co-related with increased oxygen consumption by MTII treatment. Soleus UCP3 mRNA expression was increased significantly only in the MSG-obese rats compared with pair fed rats.
CONCLUSION
These results demonstrated that both anorexic and thermogenic mechanisms were activated by MTII in the MSG-obese rats and the thermogenic activation was related with increased mRNA level of UCP1 in BAT and UCP3 in skeletal muscle.