Liraglutide improves liver microvascular dysfunction in cirrhosis: Evidence from translational studies

Abstract Hepatic stellate cells (HSC) play a key role in the development of chronic liver disease (CLD). Liraglutide, well-established in type 2 diabetes, showed anti-inflammatory and anti-oxidant properties. We evaluated the effects of liraglutide on HSC phenotype and hepatic microvascular function...

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Autores principales:	Fernanda Cristina de Mesquita, Sergi Guixé-Muntet, Anabel Fernández-Iglesias, Raquel Maeso-Díaz, Sergi Vila, Diana Hide, Martí Ortega-Ribera, José Luís Rosa, Juan Carlos García-Pagán, Jaime Bosch, Jarbas Rodrigues de Oliveira, Jordi Gracia-Sancho
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/900702cceaa04c7381a0e86421ce63a4
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spelling	oai:doaj.org-article:900702cceaa04c7381a0e86421ce63a42021-12-02T16:06:09ZLiraglutide improves liver microvascular dysfunction in cirrhosis: Evidence from translational studies10.1038/s41598-017-02866-y2045-2322https://doaj.org/article/900702cceaa04c7381a0e86421ce63a42017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02866-yhttps://doaj.org/toc/2045-2322Abstract Hepatic stellate cells (HSC) play a key role in the development of chronic liver disease (CLD). Liraglutide, well-established in type 2 diabetes, showed anti-inflammatory and anti-oxidant properties. We evaluated the effects of liraglutide on HSC phenotype and hepatic microvascular function using diverse pre-clinical models of CLD. Human and rat HSC were in vitro treated with liraglutide, or vehicle, and their phenotype, viability and proliferation were evaluated. In addition, liraglutide or vehicle was administered to rats with CLD. Liver microvascular function, fibrosis, HSC phenotype and sinusoidal endothelial phenotype were determined. Additionally, the effects of liraglutide on HSC phenotype were analysed in human precision-cut liver slices. Liraglutide markedly improved HSC phenotype and diminished cell proliferation. Cirrhotic rats receiving liraglutide exhibited significantly improved liver microvascular function, as evidenced by lower portal pressure, improved intrahepatic vascular resistance, and marked ameliorations in fibrosis, HSC phenotype and endothelial function. The anti-fibrotic effects of liraglutide were confirmed in human liver tissue and, although requiring further investigation, its underlying molecular mechanisms suggested a GLP1-R-independent and NF-κB-Sox9-dependent one. This study demonstrates for the first time that liraglutide improves the liver sinusoidal milieu in pre-clinical models of cirrhosis, encouraging its clinical evaluation in the treatment of chronic liver disease.Fernanda Cristina de MesquitaSergi Guixé-MuntetAnabel Fernández-IglesiasRaquel Maeso-DíazSergi VilaDiana HideMartí Ortega-RiberaJosé Luís RosaJuan Carlos García-PagánJaime BoschJarbas Rodrigues de OliveiraJordi Gracia-SanchoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Fernanda Cristina de Mesquita Sergi Guixé-Muntet Anabel Fernández-Iglesias Raquel Maeso-Díaz Sergi Vila Diana Hide Martí Ortega-Ribera José Luís Rosa Juan Carlos García-Pagán Jaime Bosch Jarbas Rodrigues de Oliveira Jordi Gracia-Sancho Liraglutide improves liver microvascular dysfunction in cirrhosis: Evidence from translational studies
description	Abstract Hepatic stellate cells (HSC) play a key role in the development of chronic liver disease (CLD). Liraglutide, well-established in type 2 diabetes, showed anti-inflammatory and anti-oxidant properties. We evaluated the effects of liraglutide on HSC phenotype and hepatic microvascular function using diverse pre-clinical models of CLD. Human and rat HSC were in vitro treated with liraglutide, or vehicle, and their phenotype, viability and proliferation were evaluated. In addition, liraglutide or vehicle was administered to rats with CLD. Liver microvascular function, fibrosis, HSC phenotype and sinusoidal endothelial phenotype were determined. Additionally, the effects of liraglutide on HSC phenotype were analysed in human precision-cut liver slices. Liraglutide markedly improved HSC phenotype and diminished cell proliferation. Cirrhotic rats receiving liraglutide exhibited significantly improved liver microvascular function, as evidenced by lower portal pressure, improved intrahepatic vascular resistance, and marked ameliorations in fibrosis, HSC phenotype and endothelial function. The anti-fibrotic effects of liraglutide were confirmed in human liver tissue and, although requiring further investigation, its underlying molecular mechanisms suggested a GLP1-R-independent and NF-κB-Sox9-dependent one. This study demonstrates for the first time that liraglutide improves the liver sinusoidal milieu in pre-clinical models of cirrhosis, encouraging its clinical evaluation in the treatment of chronic liver disease.
format	article
author	Fernanda Cristina de Mesquita Sergi Guixé-Muntet Anabel Fernández-Iglesias Raquel Maeso-Díaz Sergi Vila Diana Hide Martí Ortega-Ribera José Luís Rosa Juan Carlos García-Pagán Jaime Bosch Jarbas Rodrigues de Oliveira Jordi Gracia-Sancho
author_facet	Fernanda Cristina de Mesquita Sergi Guixé-Muntet Anabel Fernández-Iglesias Raquel Maeso-Díaz Sergi Vila Diana Hide Martí Ortega-Ribera José Luís Rosa Juan Carlos García-Pagán Jaime Bosch Jarbas Rodrigues de Oliveira Jordi Gracia-Sancho
author_sort	Fernanda Cristina de Mesquita
title	Liraglutide improves liver microvascular dysfunction in cirrhosis: Evidence from translational studies
title_short	Liraglutide improves liver microvascular dysfunction in cirrhosis: Evidence from translational studies
title_full	Liraglutide improves liver microvascular dysfunction in cirrhosis: Evidence from translational studies
title_fullStr	Liraglutide improves liver microvascular dysfunction in cirrhosis: Evidence from translational studies
title_full_unstemmed	Liraglutide improves liver microvascular dysfunction in cirrhosis: Evidence from translational studies
title_sort	liraglutide improves liver microvascular dysfunction in cirrhosis: evidence from translational studies
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/900702cceaa04c7381a0e86421ce63a4
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Liraglutide improves liver microvascular dysfunction in cirrhosis: Evidence from translational studies

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