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Ghrelin acts on rat dorsal vagal complex to stimulate feeding via arcuate neuropeptide Y/agouti-related peptide neurons activation

GUAN Hong-Zai, LI Qing-Chun, JIANG Zheng-Yao

Department of Physiology, Qingdao University School of Medicine, Qingdao 266071, China； Department of Reproductive Medicine, the Affiliated Hospital of Binzhou Medical College, Binzhou 256603, China

Abstract

Ghrelin, an endogenous ligand for the growth hormone secretagogue (GHS) receptor, stimulates feeding and increases bodyweight. The primary action site of ghrelin has been reported to be the neuropeptide Y (NPY)/agouti-related peptide (AgRP) neurons inthe hypothalamic arcuate nucleus (ARC). In addition to the hypothalamus, the caudal brainstem also appears to be an importantmediator for the orexigenic activity of ghrelin. However, it is not clear whether ghrelin applied directly to the caudal brainstem activatesforebrain structures. The aim of this study was to determine whether recruitment of forebrain structures was required for hyperphagicresponses stimulated by ghrelin delivery within the caudal brainstem. In our experiment, all rats were surgically implanted withindwelling cannulas in the dorsal vagal complex (DVC), and ghrelin (20 pmol in 0.5 μL) was delivered to the DVC. After the injection,the orexigenic response to ghrelin was recorded by Feeding and Activity Analyser, and NPY/AgRP mRNA expressions in rat hypothalamuswere detected by real-time PCR. In addition, the NPY immunoreactive neurons in the ARC were assayed by immunohistochemistry.The results showed that ghrelin significantly increased cumulative food intake at 1, 2 and 3 h after ghrelin injection, maximal responseoccurring at 2 h after injection. NPY/AgRP mRNA levels in ARC treated with ghrelin increased significantly compared with those incontrol group (injected with saline). The highest levels of NPY and AgRP mRNA were detected at 2 h after injection. The total numberand mean optical density of NPY-positive neurons increased in ghrelin treated rats compared with those in control group. Consistently,ghrelin’s effect was most pronounced at 2 h after injection. Taken together, we conclude that the activation of NPY/AgRP neurons inthe ARC is involved in the mediation of the hyperphagic response to brainstem ghrelin administration in neurologically intact rats.

Key words: ghrelin; food intake; dorsal vagal complex; arcuate nucleus; neuropeptide Y/agouti-related peptide; rat

Received: 2010-06-09　　Accepted: 2010-07-20

Corresponding author: 蒋正尧　　E-mail: qd-zyj@163.com

Citing This Article：

GUAN Hong-Zai, LI Qing-Chun, JIANG Zheng-Yao. Ghrelin acts on rat dorsal vagal complex to stimulate feeding via arcuate neuropeptide Y/agouti-related peptide neurons activation. Acta Physiol Sin 2010; 62 (4): 357-364 (in Chinese with English abstract).