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.
|Number of pages||8|
|Journal||Biochemical and Biophysical Research Communications|
|Publication status||Published - 2005 Apr 22|
Bibliographical noteFunding 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.
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cell Biology