Dynamic regulation of hypothalamic neuropeptide gene expression and food intake by melanocortin analogues and reversal with melanocortin-4 receptor antagonist

Ryang Yeo Kim, Seung Woo Shin, Byung Jin Kim, Weon Tae Lee, Ja Hyun Baik

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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.

Original languageEnglish
Pages (from-to)1178-1185
Number of pages8
JournalBiochemical and Biophysical Research Communications
Issue number4
Publication statusPublished - 2005 Apr 22


All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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