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Probiotics suppress nonalcoholic steatohepatitis and carcinogenesis progression in hepatocyte-specific PTEN knockout mice

Nonalcoholic fatty liver disease (NAFLD), a hepatic characteristic of metabolic syndrome, received significant attention in clinical settings. The multiple-hit theory is one of the proposed mechanisms of NAFLD, and gut dysbiosis is considered a hit. Thus, controlling gut microbiota is a potential ta...

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Autores principales: Arai, Naoshi, Miura, Kouichi, Aizawa, Kenichi, Sekiya, Mariko, Nagayama, Manabu, Sakamoto, Hirotsugu, Maeda, Hiroshi, Morimoto, Naoki, Iwamoto, Sadahiko, Yamamoto, Hironori
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9519992/
https://www.ncbi.nlm.nih.gov/pubmed/36171333
http://dx.doi.org/10.1038/s41598-022-20296-3
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author Arai, Naoshi
Miura, Kouichi
Aizawa, Kenichi
Sekiya, Mariko
Nagayama, Manabu
Sakamoto, Hirotsugu
Maeda, Hiroshi
Morimoto, Naoki
Iwamoto, Sadahiko
Yamamoto, Hironori
author_facet Arai, Naoshi
Miura, Kouichi
Aizawa, Kenichi
Sekiya, Mariko
Nagayama, Manabu
Sakamoto, Hirotsugu
Maeda, Hiroshi
Morimoto, Naoki
Iwamoto, Sadahiko
Yamamoto, Hironori
author_sort Arai, Naoshi
collection PubMed
description Nonalcoholic fatty liver disease (NAFLD), a hepatic characteristic of metabolic syndrome, received significant attention in clinical settings. The multiple-hit theory is one of the proposed mechanisms of NAFLD, and gut dysbiosis is considered a hit. Thus, controlling gut microbiota is a potential target in the management of NAFLD, and probiotics can be used as a treatment agent for NAFLD. The current study aimed to investigate the efficacy of probiotics against nonalcoholic steatohepatitis in a hepatocyte-specific PTEN knockout mouse model that mimics the characteristics of human NAFLD. Probiotics were administered to male knockout mice for 8 or 40 weeks. Next, we assessed hepatic inflammation, fibrosis, carcinogenesis, and oxidative stress. Probiotics were found to reduce serum transaminase levels, NAFLD activity score, and the gene expression of pro-inflammatory cytokines. In addition, they decreased liver fibrosis grade, which was examined via Sirius red staining, gene expression of fibrotic markers, and hydroxyproline. Furthermore, probiotics suppressed the number of liver tumors, particular in HCC. Probiotics reduced oxidative stresses, including glutathione levels, and anti-oxidative stress marker, which may be an underlying mechanism for their beneficial effects. In conclusion, probiotics treatment had beneficial effects against NAFLD and carcinogenesis in hepatocyte-specific PTEN knockout mice.
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spelling pubmed-95199922022-09-30 Probiotics suppress nonalcoholic steatohepatitis and carcinogenesis progression in hepatocyte-specific PTEN knockout mice Arai, Naoshi Miura, Kouichi Aizawa, Kenichi Sekiya, Mariko Nagayama, Manabu Sakamoto, Hirotsugu Maeda, Hiroshi Morimoto, Naoki Iwamoto, Sadahiko Yamamoto, Hironori Sci Rep Article Nonalcoholic fatty liver disease (NAFLD), a hepatic characteristic of metabolic syndrome, received significant attention in clinical settings. The multiple-hit theory is one of the proposed mechanisms of NAFLD, and gut dysbiosis is considered a hit. Thus, controlling gut microbiota is a potential target in the management of NAFLD, and probiotics can be used as a treatment agent for NAFLD. The current study aimed to investigate the efficacy of probiotics against nonalcoholic steatohepatitis in a hepatocyte-specific PTEN knockout mouse model that mimics the characteristics of human NAFLD. Probiotics were administered to male knockout mice for 8 or 40 weeks. Next, we assessed hepatic inflammation, fibrosis, carcinogenesis, and oxidative stress. Probiotics were found to reduce serum transaminase levels, NAFLD activity score, and the gene expression of pro-inflammatory cytokines. In addition, they decreased liver fibrosis grade, which was examined via Sirius red staining, gene expression of fibrotic markers, and hydroxyproline. Furthermore, probiotics suppressed the number of liver tumors, particular in HCC. Probiotics reduced oxidative stresses, including glutathione levels, and anti-oxidative stress marker, which may be an underlying mechanism for their beneficial effects. In conclusion, probiotics treatment had beneficial effects against NAFLD and carcinogenesis in hepatocyte-specific PTEN knockout mice. Nature Publishing Group UK 2022-09-28 /pmc/articles/PMC9519992/ /pubmed/36171333 http://dx.doi.org/10.1038/s41598-022-20296-3 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Arai, Naoshi
Miura, Kouichi
Aizawa, Kenichi
Sekiya, Mariko
Nagayama, Manabu
Sakamoto, Hirotsugu
Maeda, Hiroshi
Morimoto, Naoki
Iwamoto, Sadahiko
Yamamoto, Hironori
Probiotics suppress nonalcoholic steatohepatitis and carcinogenesis progression in hepatocyte-specific PTEN knockout mice
title Probiotics suppress nonalcoholic steatohepatitis and carcinogenesis progression in hepatocyte-specific PTEN knockout mice
title_full Probiotics suppress nonalcoholic steatohepatitis and carcinogenesis progression in hepatocyte-specific PTEN knockout mice
title_fullStr Probiotics suppress nonalcoholic steatohepatitis and carcinogenesis progression in hepatocyte-specific PTEN knockout mice
title_full_unstemmed Probiotics suppress nonalcoholic steatohepatitis and carcinogenesis progression in hepatocyte-specific PTEN knockout mice
title_short Probiotics suppress nonalcoholic steatohepatitis and carcinogenesis progression in hepatocyte-specific PTEN knockout mice
title_sort probiotics suppress nonalcoholic steatohepatitis and carcinogenesis progression in hepatocyte-specific pten knockout mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9519992/
https://www.ncbi.nlm.nih.gov/pubmed/36171333
http://dx.doi.org/10.1038/s41598-022-20296-3
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