Characterization of MCH-mediated obesity in mice.
Melanin-concentrating hormone (MCH) is a cyclic orexigenic peptide expressed in the lateral hypothalamus. Recently, we demonstrated that chronic intracerebroventricular infusion of MCH induced obesity accompanied by sustained hyperphagia in mice. Here, we analyzed the mechanism of MCH-induced obesity by comparing animals fed ad libitum with pair-fed and control animals. Chronic infusion of MCH significantly increased food intake, body weight, white adipose tissue (WAT) mass, and liver mass in ad libitum-fed mice on a moderately high-fat diet. In addition, a significant increase in lipogenic activity was observed in the WAT of the ad libitum-fed group. Although body weight gain was marginal in the pair-fed group, MCH infusion clearly enhanced the lipogenic activity in liver and WAT. Plasma leptin levels were also increased in the pair-fed group. Furthermore, MCH infusion significantly reduced rectal temperatures in the pair-fed group. In support of these findings, mRNA expression of uncoupling protein-1, acyl-CoA oxidase, and carnitine palmitoyltransferase I, which are key molecules involved in thermogenesis and fatty acid oxidation, were reduced in the brown adipose tissue (BAT) of the pair-fed group, suggesting that MCH infusion might reduce BAT functions. We conclude that the activation of MCH neuronal pathways stimulated adiposity, in part resulting from increased lipogenesis in liver and WAT and reduced energy expenditure in BAT. These findings confirm that modulation of energy homeostasis by MCH may play a critical role in the development of obesity.
Ito
Masahiko
M
Tsukuba Research Institute, Banyu Pharmaceutical Co., Ltd., Okubo 3, Tsukuba 300-2611, Japan.
Gomori
Akira
A
Ishihara
Akane
A
Oda
Zenjun
Z
Mashiko
Satoshi
S
Matsushita
Hiroko
H
Yumoto
Mariko
M
Ito
Makoto
M
Sano
Hideki
H
Tokita
Shigeru
S
Moriya
Minoru
M
Iwaasa
Hisashi
H
Kanatani
Akio
A
D000273:Adipose Tissue / Q000503:physiopathology; D002001:Adipose Tissue, Brown / Q000378:metabolism; D000818:Animals; D001831:Body Temperature; D001835:Body Weight; D004435:Eating; D005227:Fatty Acids / Q000378:metabolism; D007028:Hypothalamic Hormones / Q000008:administration & dosage*; D007276:Injections, Intraventricular; D008055:Lipids / Q000096:biosynthesis; D008099:Liver / Q000378:metabolism; D008297:Male; D008543:Melanins / Q000008:administration & dosage*; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology*; D009929:Organ Size; D010084:Oxidation-Reduction; D010907:Pituitary Hormones / Q000008:administration & dosage*; D012007:Rectum / Q000503:physiopathology
D005227:Fatty Acids; D007028:Hypothalamic Hormones; D008055:Lipids; D008543:Melanins; D010907:Pituitary Hormones; C019463:melanin-concentrating hormone