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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

2001; American Diabetes Association; Volume: 50; Issue: 2 Linguagem: Inglês

10.2337/diabetes.50.2.227

1939-327X

Mitsuyo Shintani, Yoshihiro Ogawa, Ken Ebihara, Megumi Aizawa‐Abe, Fumiko Miyanaga, Kazuhiko Takaya, Tatsuya Hayashi, Gen Inoue, Kiminori Hosoda, Masayasu Kojima, Kenji Kangawa, Kazuwa Nakao,

Hypothalamic control of reproductive hormones

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) (∼ 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 μg/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.