Exendin-4 reduces food intake via the PI3K/AKT signaling pathway in the hypothalamus

Abstract Exendin-4 (EX-4), a glucagon-like peptide-1 (GLP-1) receptor agonist, has been shown to reduce food intake and to increase proopiomelanocortin (POMC) gene expression in the hypothalamus. In this study, we examined the potential neural mechanisms by which these effects occur. Male Sprague Da...

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Autores principales:	Yan Yang, Pique P. Choi, Wanli W. Smith, Weijie Xu, Delin Ma, Zachary A. Cordner, Nu-Chu Liang, Timothy H. Moran
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2b30cf5ad9e742a785d581812b760db1
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spelling	oai:doaj.org-article:2b30cf5ad9e742a785d581812b760db12021-12-02T11:52:58ZExendin-4 reduces food intake via the PI3K/AKT signaling pathway in the hypothalamus10.1038/s41598-017-06951-02045-2322https://doaj.org/article/2b30cf5ad9e742a785d581812b760db12017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06951-0https://doaj.org/toc/2045-2322Abstract Exendin-4 (EX-4), a glucagon-like peptide-1 (GLP-1) receptor agonist, has been shown to reduce food intake and to increase proopiomelanocortin (POMC) gene expression in the hypothalamus. In this study, we examined the potential neural mechanisms by which these effects occur. Male Sprague Dawley rats were implanted with a cannula in the third ventricle of the brain through which an inhibitor of phosphatidylinositol-3 kinase (PI3K) (wortmannin) was administered, and EX-4 or vehicle was administered via intraperitoneal (IP) injection. The activity of PI3K/protein kinase B (AKT) and insulin receptor substrate-1 (IRS-1) in the hypothalamic arcuate was determined. We found that EX-4 treatment significantly decreased food intake and body weight. However, there were almost no changes in food intake and body weight when wortmannin injection (into the third ventricle) occurred prior to EX-4 IP injection. EX-4 not only increased the activity of PI3K/AKT, but it also increased IRS-1 activity. These results show that EX-4 likely suppresses food intake due to its ability to enhance insulin signaling.Yan YangPique P. ChoiWanli W. SmithWeijie XuDelin MaZachary A. CordnerNu-Chu LiangTimothy H. MoranNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-7 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yan Yang Pique P. Choi Wanli W. Smith Weijie Xu Delin Ma Zachary A. Cordner Nu-Chu Liang Timothy H. Moran Exendin-4 reduces food intake via the PI3K/AKT signaling pathway in the hypothalamus
description	Abstract Exendin-4 (EX-4), a glucagon-like peptide-1 (GLP-1) receptor agonist, has been shown to reduce food intake and to increase proopiomelanocortin (POMC) gene expression in the hypothalamus. In this study, we examined the potential neural mechanisms by which these effects occur. Male Sprague Dawley rats were implanted with a cannula in the third ventricle of the brain through which an inhibitor of phosphatidylinositol-3 kinase (PI3K) (wortmannin) was administered, and EX-4 or vehicle was administered via intraperitoneal (IP) injection. The activity of PI3K/protein kinase B (AKT) and insulin receptor substrate-1 (IRS-1) in the hypothalamic arcuate was determined. We found that EX-4 treatment significantly decreased food intake and body weight. However, there were almost no changes in food intake and body weight when wortmannin injection (into the third ventricle) occurred prior to EX-4 IP injection. EX-4 not only increased the activity of PI3K/AKT, but it also increased IRS-1 activity. These results show that EX-4 likely suppresses food intake due to its ability to enhance insulin signaling.
format	article
author	Yan Yang Pique P. Choi Wanli W. Smith Weijie Xu Delin Ma Zachary A. Cordner Nu-Chu Liang Timothy H. Moran
author_facet	Yan Yang Pique P. Choi Wanli W. Smith Weijie Xu Delin Ma Zachary A. Cordner Nu-Chu Liang Timothy H. Moran
author_sort	Yan Yang
title	Exendin-4 reduces food intake via the PI3K/AKT signaling pathway in the hypothalamus
title_short	Exendin-4 reduces food intake via the PI3K/AKT signaling pathway in the hypothalamus
title_full	Exendin-4 reduces food intake via the PI3K/AKT signaling pathway in the hypothalamus
title_fullStr	Exendin-4 reduces food intake via the PI3K/AKT signaling pathway in the hypothalamus
title_full_unstemmed	Exendin-4 reduces food intake via the PI3K/AKT signaling pathway in the hypothalamus
title_sort	exendin-4 reduces food intake via the pi3k/akt signaling pathway in the hypothalamus
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/2b30cf5ad9e742a785d581812b760db1
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Exendin-4 reduces food intake via the PI3K/AKT signaling pathway in the hypothalamus

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