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Biochem Biophys Res Commun. 2014 Aug 22;451(2):276-81. doi: 10.1016/j.bbrc.2014.07.116. Epub 2014 Aug 1.

Endogenous GLP-1 acts on paraventricular nucleus to suppress feeding: projection from nucleus tractus solitarius and activation of corticotropin-releasing hormone, nesfatin-1 and oxytocin neurons.

Author information

1
Division of Integrative Physiology, Department of Physiology, Jichi Medical University School of Medicine, 3311-1 Shimotsuke, Tochigi 329-0498, Japan; Division of Cardiovascular Medicine, Department of Internal Medicine, Jichi Medical University School of Medicine, 3311-1 Shimotsuke, Tochigi 329-0498, Japan.
2
Division of Integrative Physiology, Department of Physiology, Jichi Medical University School of Medicine, 3311-1 Shimotsuke, Tochigi 329-0498, Japan.
3
Division of Cardiovascular Medicine, Department of Internal Medicine, Jichi Medical University School of Medicine, 3311-1 Shimotsuke, Tochigi 329-0498, Japan.
4
Division of Integrative Physiology, Department of Physiology, Jichi Medical University School of Medicine, 3311-1 Shimotsuke, Tochigi 329-0498, Japan; Department of Development Physiology, Division of Adaptation Development, National Institute for Physiological Science, Okazaki, Aichi 444-8585, Japan. Electronic address: tyada@jichi.ac.jp.

Abstract

Glucagon-like peptide-1 (GLP-1) receptor agonists have been used to treat type 2 diabetic patients and shown to reduce food intake and body weight. The anorexigenic effects of GLP-1 and GLP-1 receptor agonists are thought to be mediated primarily via the hypothalamic paraventricular nucleus (PVN). GLP-1, an intestinal hormone, is also localized in the nucleus tractus solitarius (NTS) of the brain stem. However, the role of endogenous GLP-1, particularly that in the NTS neurons, in feeding regulation remains to be established. The present study examined whether the NTS GLP-1 neurons project to PVN and whether the endogenous GLP-1 acts on PVN to restrict feeding. Intra-PVN injection of GLP-1 receptor antagonist exendin (9-39) increased food intake. Injection of retrograde tracer into PVN combined with immunohistochemistry for GLP-1 in NTS revealed direct projection of NTS GLP-1 neurons to PVN. Moreover, GLP-1 evoked Ca(2+) signaling in single neurons isolated from PVN. The majority of GLP-1-responsive neurons were immunoreactive predominantly to corticotropin-releasing hormone (CRH) and nesfatin-1, and less frequently to oxytocin. These results indicate that endogenous GLP-1 targets PVN to restrict feeding behavior, in which the projection from NTS GLP-1 neurons and activation of CRH and nesfatin-1 neurons might be implicated. This study reveals a neuronal basis for the anorexigenic effect of endogenous GLP-1 in the brain.

KEYWORDS:

Corticotropin-releasing hormone; Feeding; Glucagon-like peptide-1; Nesfatin-1; Nucleus tractus solitarius; Paraventricular nucleus

PMID:
25089000
DOI:
10.1016/j.bbrc.2014.07.116
[Indexed for MEDLINE]

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