TY - JOUR
T1 - Dynamic regulation of hypothalamic neuropeptide gene expression and food intake by melanocortin analogues and reversal with melanocortin-4 receptor antagonist
AU - Kim, Ryang Yeo
AU - Shin, Seung Woo
AU - Kim, Byung Jin
AU - Lee, Weontae
AU - Baik, Ja Hyun
N1 - Funding Information:
We thank Dr. R. Thompson (University of Michigan, USA), Dr. S. Sabol (NIH, USA) Dr. Robert Steiner (University of Washington), Dr. G. Barsh (Stanford University), and Dr. Jacques Drouin (Institut de Recherches Cliniques de Montréal, Canada) for providing us with the MCH, NPY, galanin, and Mahogany and POMC cDNAs, respectively. R.Y. Kim., S.W. Shin, and B.-J. Kim are the recipients of a Brain Korea 21 program from the Korean Ministry of Education. This work was supported by a research grant from the 2003 Good Health R&D Project (Grant No. 03-PJ1-PG1-CH05-0005), Ministry of Health and Welfare, South Korea.
PY - 2005/4/22
Y1 - 2005/4/22
N2 - Melanocortins are known to be involved in the inhibition of food intake and energy metabolism. Acute and chronic intracerebroventricular administration of several different analogues of α-MSH, such as α-MSH, NDP-MSH, α-MSH-ND, [Gln6]α-MSH-ND, and [Lys6]α- MSH-ND, which were substituted in the position of His6 with Gln and Lys, and cyclic16k-MSH to C57J/BL6 mice resulted in a significant inhibition of both time course food intake and body weight gain, compared to the saline-administered control. However, [Gln6]α-MSH-ND(6-10), the truncated form of [Gln6]α-MSH-ND, had no inhibitory effects on food intake. In situ hybridization analysis revealed that the expression levels of AGRP and NPY in the hypothalamus were significantly and rapidly diminished while POMC expression was strongly induced by [Gln6]α-MSH-ND. Administration of JKC-363, a selective MC4R-specific antagonist, coupled with [Gln6]α-MSH-ND, specifically reversed the [Gln 6]α-MSH-ND-induced inhibition of food intake, but also reversed the hypothalamic expression levels of neuropeptides such as AGRP, NPY, MCH, and POMC, which suggests [Gln6]α-MSH-ND can function as a selective MC4R agonist.
AB - Melanocortins are known to be involved in the inhibition of food intake and energy metabolism. Acute and chronic intracerebroventricular administration of several different analogues of α-MSH, such as α-MSH, NDP-MSH, α-MSH-ND, [Gln6]α-MSH-ND, and [Lys6]α- MSH-ND, which were substituted in the position of His6 with Gln and Lys, and cyclic16k-MSH to C57J/BL6 mice resulted in a significant inhibition of both time course food intake and body weight gain, compared to the saline-administered control. However, [Gln6]α-MSH-ND(6-10), the truncated form of [Gln6]α-MSH-ND, had no inhibitory effects on food intake. In situ hybridization analysis revealed that the expression levels of AGRP and NPY in the hypothalamus were significantly and rapidly diminished while POMC expression was strongly induced by [Gln6]α-MSH-ND. Administration of JKC-363, a selective MC4R-specific antagonist, coupled with [Gln6]α-MSH-ND, specifically reversed the [Gln 6]α-MSH-ND-induced inhibition of food intake, but also reversed the hypothalamic expression levels of neuropeptides such as AGRP, NPY, MCH, and POMC, which suggests [Gln6]α-MSH-ND can function as a selective MC4R agonist.
KW - Gene expression
KW - Hypothalamus
KW - Melanocortin
KW - Obesity
UR - http://www.scopus.com/inward/record.url?scp=17644366147&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2005.02.105
DO - 10.1016/j.bbrc.2005.02.105
M3 - Article
C2 - 15766551
AN - SCOPUS:17644366147
VL - 329
SP - 1178
EP - 1185
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 4
ER -
