Leptin-like effects of MTII are augmented in MSG-obese rats.
To evaluate whether MTII, a melanocortin receptor 3/4 agonist, is working in hypophagic and hypothermogenic obese model, we measured food intake, body weight, oxygen consumption, and fat mass following 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 an osmotic minipump for 1 week. MSG-obese rats were induced by neonatal injection of MSG. Five-month-old MSG rats were characterized by hypophagia, lower oxygen consumption, hyperleptinemia, and obesity compared to age-matched control rats. The infusion of MTII decreased their 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 (PF) rats. Interestingly, these leptin-like effects of MTII were greater in MSG-obese rats than in controls, which might be related to the increased expression of melanocortin receptor 4 (MC4R) in the hypothalamus of MSG-obese rats. Our results suggested that both anorexic and thermogenic mechanisms were activated by MTII in the MSG-obese rats and contributed to the decrease in body weight and fat mass. Moreover, there was a sensitization to MTII caused by upregulation of the melanocortin receptor in the MSG-obese rats.
Kim
Yong-Woon
YW
Department of Physiology, College of Medicine, Yeungnam University, #317-1, Daemyungdong, Namgu, Daegu 705-717, Republic of Korea. ywkim@med.yu.ac.kr
Choi
Dong-Weon
DW
Park
Yong-Hoon
YH
Huh
Jung-Yoon
JY
Won
Kyu-Chang
KC
Choi
Kwang-Hae
KH
Park
So-Young
SY
Kim
Jong-Yeon
JY
Lee
Suck-Kang
SK
D000818:Animals; D001835:Body Weight; D002245:Carbon Dioxide / Q000378:metabolism; D004435:Eating; D005230:Fatty Acids, Nonesterified; D005260:Female; D005503:Food Additives / Q000008:administration & dosage; D006801:Humans; D020738:Leptin / Q000378:metabolism*; D008297:Male; D009765:Obesity / Q000139:chemically induced / Q000378:metabolism*; D010101:Oxygen Consumption; D011247:Pregnancy; D011333:Pro-Opiomelanocortin / Q000235:genetics / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D044105:Receptor, Melanocortin, Type 4 / Q000235:genetics / Q000378:metabolism; D054411:Receptors, Leptin; D012970:Sodium Glutamate / Q000008:administration & dosage; D000521:alpha-MSH / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism
D005230:Fatty Acids, Nonesterified; D005503:Food Additives; C515448:LEPR protein, human; D020738:Leptin; D044105:Receptor, Melanocortin, Type 4; D054411:Receptors, Leptin; C105974:acetyl-norleucyl(4)-(aspartyl(5)-histidyl(6)-phenylalanyl(7)-arginyl(8)-tryptophyl(9)-lysyl(10))cyclo-alpha-MSH(4-10)amide; D002245:Carbon Dioxide; D000521:alpha-MSH; D011333:Pro-Opiomelanocortin; D012970:Sodium Glutamate