Hepatic galectin-3 is associated with lipid droplet area in non-alcoholic steatohepatitis in a new swine model

Abstract Non-alcoholic fatty liver disease (NAFLD) is currently a growing epidemic disease that can lead to cirrhosis and hepatic cancer when it evolves into non-alcoholic steatohepatitis (NASH), a gap not well understood. To characterize this disease, pigs, considered to be one of the most similar...

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Main Authors: Luis V. Herrera-Marcos, Roberto Martínez-Beamonte, Manuel Macías-Herranz, Carmen Arnal, Cristina Barranquero, Juan J. Puente-Lanzarote, Sonia Gascón, Tania Herrero-Continente, Gonzalo Gonzalo-Romeo, Víctor Alastrué-Vera, Dolores Gutiérrez-Blázquez, José M. Lou-Bonafonte, Joaquín C. Surra, María J. Rodríguez-Yoldi, Agustín García-Gil, Antonio Güemes, Jesús Osada
Format: Article
Language:English
Published: Nature Portfolio 2022-01-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-022-04971-z
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author Luis V. Herrera-Marcos
Roberto Martínez-Beamonte
Manuel Macías-Herranz
Carmen Arnal
Cristina Barranquero
Juan J. Puente-Lanzarote
Sonia Gascón
Tania Herrero-Continente
Gonzalo Gonzalo-Romeo
Víctor Alastrué-Vera
Dolores Gutiérrez-Blázquez
José M. Lou-Bonafonte
Joaquín C. Surra
María J. Rodríguez-Yoldi
Agustín García-Gil
Antonio Güemes
Jesús Osada
author_facet Luis V. Herrera-Marcos
Roberto Martínez-Beamonte
Manuel Macías-Herranz
Carmen Arnal
Cristina Barranquero
Juan J. Puente-Lanzarote
Sonia Gascón
Tania Herrero-Continente
Gonzalo Gonzalo-Romeo
Víctor Alastrué-Vera
Dolores Gutiérrez-Blázquez
José M. Lou-Bonafonte
Joaquín C. Surra
María J. Rodríguez-Yoldi
Agustín García-Gil
Antonio Güemes
Jesús Osada
author_sort Luis V. Herrera-Marcos
collection DOAJ
description Abstract Non-alcoholic fatty liver disease (NAFLD) is currently a growing epidemic disease that can lead to cirrhosis and hepatic cancer when it evolves into non-alcoholic steatohepatitis (NASH), a gap not well understood. To characterize this disease, pigs, considered to be one of the most similar to human experimental animal models, were used. To date, all swine-based settings have been carried out using rare predisposed breeds or long-term experiments. Herein, we fully describe a new experimental swine model for initial and reversible NASH using cross-bred animals fed on a high saturated fat, fructose, cholesterol, cholate, choline and methionine-deficient diet. To gain insight into the hepatic transcriptome that undergoes steatosis and steatohepatitis, we used RNA sequencing. This process significantly up-regulated 976 and down-regulated 209 genes mainly involved in cellular processes. Gene expression changes of 22 selected transcripts were verified by RT-qPCR. Lipid droplet area was positively associated with CD68, GPNMB, LGALS3, SLC51B and SPP1, and negatively with SQLE expressions. When these genes were tested in a second experiment of NASH reversion, LGALS3, SLC51B and SPP1 significantly decreased their expression. However, only LGALS3 was associated with lipid droplet areas. Our results suggest a role for LGALS3 in the transition of NAFLD to NASH.
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spelling doaj.art-5bc1f80a5eda47a8860a5cd2f123e2762022-12-22T04:09:54ZengNature PortfolioScientific Reports2045-23222022-01-0112111710.1038/s41598-022-04971-zHepatic galectin-3 is associated with lipid droplet area in non-alcoholic steatohepatitis in a new swine modelLuis V. Herrera-Marcos0Roberto Martínez-Beamonte1Manuel Macías-Herranz2Carmen Arnal3Cristina Barranquero4Juan J. Puente-Lanzarote5Sonia Gascón6Tania Herrero-Continente7Gonzalo Gonzalo-Romeo8Víctor Alastrué-Vera9Dolores Gutiérrez-Blázquez10José M. Lou-Bonafonte11Joaquín C. Surra12María J. Rodríguez-Yoldi13Agustín García-Gil14Antonio Güemes15Jesús Osada16Departamento de Bioquímica y Biología Molecular y Celular, Facultad de Veterinaria, Instituto de Investigación Sanitaria de Aragón-Universidad de ZaragozaDepartamento de Bioquímica y Biología Molecular y Celular, Facultad de Veterinaria, Instituto de Investigación Sanitaria de Aragón-Universidad de ZaragozaDepartamento de Bioquímica y Biología Molecular y Celular, Facultad de Veterinaria, Instituto de Investigación Sanitaria de Aragón-Universidad de ZaragozaInstituto Agroalimentario de Aragón, CITA-Universidad de ZaragozaDepartamento de Bioquímica y Biología Molecular y Celular, Facultad de Veterinaria, Instituto de Investigación Sanitaria de Aragón-Universidad de ZaragozaServicio de Bioquímica Clínica. Hospital, Clínico Universitario Lozano BlesaDepartamento de Farmacología, Fisiología, Medicina Legal y Forense, Instituto de Investigación Sanitaria de Aragón-Universidad de ZaragozaDepartamento de Bioquímica y Biología Molecular y Celular, Facultad de Veterinaria, Instituto de Investigación Sanitaria de Aragón-Universidad de ZaragozaServicio General de Apoyo a la Investigación. División de Experimentación Animal, Universidad de ZaragozaEbers Medical TechnologyUnidad de Proteómica, Universidad Complutense de MadridInstituto Agroalimentario de Aragón, CITA-Universidad de ZaragozaInstituto Agroalimentario de Aragón, CITA-Universidad de ZaragozaInstituto Agroalimentario de Aragón, CITA-Universidad de ZaragozaDepartamento de Cirugía, Facultad de Medicina, Instituto de Investigación Sanitaria de Aragón-Universidad de ZaragozaDepartamento de Cirugía, Facultad de Medicina, Instituto de Investigación Sanitaria de Aragón-Universidad de ZaragozaDepartamento de Bioquímica y Biología Molecular y Celular, Facultad de Veterinaria, Instituto de Investigación Sanitaria de Aragón-Universidad de ZaragozaAbstract Non-alcoholic fatty liver disease (NAFLD) is currently a growing epidemic disease that can lead to cirrhosis and hepatic cancer when it evolves into non-alcoholic steatohepatitis (NASH), a gap not well understood. To characterize this disease, pigs, considered to be one of the most similar to human experimental animal models, were used. To date, all swine-based settings have been carried out using rare predisposed breeds or long-term experiments. Herein, we fully describe a new experimental swine model for initial and reversible NASH using cross-bred animals fed on a high saturated fat, fructose, cholesterol, cholate, choline and methionine-deficient diet. To gain insight into the hepatic transcriptome that undergoes steatosis and steatohepatitis, we used RNA sequencing. This process significantly up-regulated 976 and down-regulated 209 genes mainly involved in cellular processes. Gene expression changes of 22 selected transcripts were verified by RT-qPCR. Lipid droplet area was positively associated with CD68, GPNMB, LGALS3, SLC51B and SPP1, and negatively with SQLE expressions. When these genes were tested in a second experiment of NASH reversion, LGALS3, SLC51B and SPP1 significantly decreased their expression. However, only LGALS3 was associated with lipid droplet areas. Our results suggest a role for LGALS3 in the transition of NAFLD to NASH.https://doi.org/10.1038/s41598-022-04971-z
spellingShingle Luis V. Herrera-Marcos
Roberto Martínez-Beamonte
Manuel Macías-Herranz
Carmen Arnal
Cristina Barranquero
Juan J. Puente-Lanzarote
Sonia Gascón
Tania Herrero-Continente
Gonzalo Gonzalo-Romeo
Víctor Alastrué-Vera
Dolores Gutiérrez-Blázquez
José M. Lou-Bonafonte
Joaquín C. Surra
María J. Rodríguez-Yoldi
Agustín García-Gil
Antonio Güemes
Jesús Osada
Hepatic galectin-3 is associated with lipid droplet area in non-alcoholic steatohepatitis in a new swine model
Scientific Reports
title Hepatic galectin-3 is associated with lipid droplet area in non-alcoholic steatohepatitis in a new swine model
title_full Hepatic galectin-3 is associated with lipid droplet area in non-alcoholic steatohepatitis in a new swine model
title_fullStr Hepatic galectin-3 is associated with lipid droplet area in non-alcoholic steatohepatitis in a new swine model
title_full_unstemmed Hepatic galectin-3 is associated with lipid droplet area in non-alcoholic steatohepatitis in a new swine model
title_short Hepatic galectin-3 is associated with lipid droplet area in non-alcoholic steatohepatitis in a new swine model
title_sort hepatic galectin 3 is associated with lipid droplet area in non alcoholic steatohepatitis in a new swine model
url https://doi.org/10.1038/s41598-022-04971-z
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