Abstract
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 language | English |
|---|---|
| Pages (from-to) | 1178-1185 |
| Number of pages | 8 |
| Journal | Biochemical and Biophysical Research Communications |
| Volume | 329 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 2005 Apr 22 |
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Keywords
- Gene expression
- Hypothalamus
- Melanocortin
- Obesity
ASJC Scopus subject areas
- Biochemistry
- Biophysics
- Molecular Biology
Cite this
Dynamic regulation of hypothalamic neuropeptide gene expression and food intake by melanocortin analogues and reversal with melanocortin-4 receptor antagonist. / Kim, Ryang Yeo; Shin, Seung Woo; Kim, Byung Jin; Lee, Weontae; Baik, Ja-Hyun.
In: Biochemical and Biophysical Research Communications, Vol. 329, No. 4, 22.04.2005, p. 1178-1185.Research output: Contribution to journal › Article
}
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
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
UR - http://www.scopus.com/inward/citedby.url?scp=17644366147&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2005.02.105
DO - 10.1016/j.bbrc.2005.02.105
M3 - Article
VL - 329
SP - 1178
EP - 1185
JO - The BMJ
JF - The BMJ
SN - 0730-6512
IS - 4
ER -