J Korean Soc Study Obes.  2004 Jun;13(2):101-109.

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

Affiliations
  • 1Department of Obstetrics, College of Medicine, Yeungnam University, Korea. ywkim@med.yu.ac.kr,
  • 2Gynecology and Physiology, College of Medicine, Yeungnam University, Korea.

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.

Keyword

Obesity; Thermogenesis; Appetite; Leptin

MeSH Terms

Adipose Tissue
Adipose Tissue, Brown
alpha-MSH
Animals
Appetite
Arcuate Nucleus
Body Weight
Diethylpropion
Eating
Energy Metabolism
Homeostasis
Hypothalamus
Infusions, Intraventricular*
Intra-Abdominal Fat
Leptin
Muscle, Skeletal
Neurons
Obesity
Oxygen Consumption
Paraventricular Hypothalamic Nucleus
Pro-Opiomelanocortin
Rats*
Receptors, Leptin
Receptors, Melanocortin
RNA, Messenger
Rodentia
Sodium Glutamate
Thermogenesis
Diethylpropion
Leptin
Pro-Opiomelanocortin
RNA, Messenger
Receptors, Leptin
Receptors, Melanocortin
Sodium Glutamate
alpha-MSH
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