Ghrelin, an endogenous growth hormone secretagogue, is a novel orexigenic peptide that antagonizes leptin action through the activation of hypothalamic neuropeptide Y/Y1 receptor pathway.

Autor: Shintani, Mitsuyo, Ogawa, Yoshihiro, Ebihara, Ken, Alzawa-Abe, Megumi, Miyanaga, Fumiko, Takaya, Kazuhiko, Hayashi, Tatsuya, Inoue, Gen, Hosoda, Kiminori, Kojima, Masayasu, Kangawa, Kenji, Nakao, Kazuwa, Shintani, M, Ogawa, Y, Ebihara, K, Aizawa-Abe, M, Miyanaga, F, Takaya, K, Hayashi, T, Inoue, G
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Zdroj: Diabetes; Feb2001, Vol. 50 Issue 2, p227-232, 6p
Abstrakt: Ghrelin, an endogenous ligand for growth hormone secretagogue (GHS) receptor originally isolated from the stomach, occurs in the hypothalamic arcuate nucleus and may play a role in energy homeostasis. Synthetic GHSs have activated the hypothalamic arcuate neurons containing neuropeptide Y (NPY), suggesting the involvement of NPY in some of ghrelin actions. This study was designed to elucidate the role of ghrelin in the regulation of food intake. A single intracerebroventricular (ICV) injection of ghrelin (5-5,000 ng/rat) caused a significant and dose-related increase in cumulative food intake in rats. Ghrelin (500 ng/rat) was also effective in growth hormone-deficient spontaneous dwarf rats. Hypothalamic NPY mRNA expression was increased in rats that received a single ICV injection of ghrelin (500 ng/rat) (approximately 160% of that in vehicle-treated groups, P < 0.05). The ghrelin's orexigenic effect was abolished dose-dependently by ICV co-injection of NPY Y1 receptor antagonist (10-30 microg/rat). The leptin-induced inhibition of food intake was reversed by ICV co-injection of ghrelin in a dose-dependent manner (5-500 ng/rat). Leptin reduced hypothalamic NPY mRNA expression by 35% (P < 0.05), which was abolished by ICV co-injection of ghrelin (500 ng/rat). This study provides evidence that ghrelin is an orexigenic peptide that antagonizes leptin action through the activation of hypothalamic NPY/Y1 receptor pathway. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index