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Mechanisms of liver injury in high fat sugar diet fed mice that lack hepatocyte X-box binding protein 1
Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of liver diseases in the United States and can progress to cirrhosis, end-stage liver disease and need for liver transplantation. There are limited therapies for NAFLD, in part, due to incomplete understanding of the disease p...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8759640/ https://www.ncbi.nlm.nih.gov/pubmed/35030194 http://dx.doi.org/10.1371/journal.pone.0261789 |
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author | Liu, Xiaoying Taylor, Sarah A. Gromer, Kyle D. Zhang, Danny Hubchak, Susan C. LeCuyer, Brian E. Iwawaki, Takao Shi, Zengdun Rockey, Don C. Green, Richard M. |
author_facet | Liu, Xiaoying Taylor, Sarah A. Gromer, Kyle D. Zhang, Danny Hubchak, Susan C. LeCuyer, Brian E. Iwawaki, Takao Shi, Zengdun Rockey, Don C. Green, Richard M. |
author_sort | Liu, Xiaoying |
collection | PubMed |
description | Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of liver diseases in the United States and can progress to cirrhosis, end-stage liver disease and need for liver transplantation. There are limited therapies for NAFLD, in part, due to incomplete understanding of the disease pathogenesis, which involves different cell populations in the liver. Endoplasmic reticulum stress and its adaptative unfolded protein response (UPR) signaling pathway have been implicated in the progression from simple hepatic steatosis to nonalcoholic steatohepatitis (NASH). We have previously shown that mice lacking the UPR protein X-box binding protein 1 (XBP1) in the liver demonstrated enhanced liver injury and fibrosis in a high fat sugar (HFS) dietary model of NAFLD. In this study, to better understand the role of liver XBP1 in the pathobiology of NAFLD, we fed hepatocyte XBP1 deficient mice a HFS diet or chow and investigated UPR and other cell signaling pathways in hepatocytes, hepatic stellate cells and immune cells. We demonstrate that loss of XBP1 in hepatocytes increased inflammatory pathway expression and altered expression of the UPR signaling in hepatocytes and was associated with enhanced hepatic stellate cell activation after HFS feeding. We believe that a better understanding of liver cell-specific signaling in the pathogenesis of NASH may allow us to identify new therapeutic targets. |
format | Online Article Text |
id | pubmed-8759640 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-87596402022-01-15 Mechanisms of liver injury in high fat sugar diet fed mice that lack hepatocyte X-box binding protein 1 Liu, Xiaoying Taylor, Sarah A. Gromer, Kyle D. Zhang, Danny Hubchak, Susan C. LeCuyer, Brian E. Iwawaki, Takao Shi, Zengdun Rockey, Don C. Green, Richard M. PLoS One Research Article Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of liver diseases in the United States and can progress to cirrhosis, end-stage liver disease and need for liver transplantation. There are limited therapies for NAFLD, in part, due to incomplete understanding of the disease pathogenesis, which involves different cell populations in the liver. Endoplasmic reticulum stress and its adaptative unfolded protein response (UPR) signaling pathway have been implicated in the progression from simple hepatic steatosis to nonalcoholic steatohepatitis (NASH). We have previously shown that mice lacking the UPR protein X-box binding protein 1 (XBP1) in the liver demonstrated enhanced liver injury and fibrosis in a high fat sugar (HFS) dietary model of NAFLD. In this study, to better understand the role of liver XBP1 in the pathobiology of NAFLD, we fed hepatocyte XBP1 deficient mice a HFS diet or chow and investigated UPR and other cell signaling pathways in hepatocytes, hepatic stellate cells and immune cells. We demonstrate that loss of XBP1 in hepatocytes increased inflammatory pathway expression and altered expression of the UPR signaling in hepatocytes and was associated with enhanced hepatic stellate cell activation after HFS feeding. We believe that a better understanding of liver cell-specific signaling in the pathogenesis of NASH may allow us to identify new therapeutic targets. Public Library of Science 2022-01-14 /pmc/articles/PMC8759640/ /pubmed/35030194 http://dx.doi.org/10.1371/journal.pone.0261789 Text en © 2022 Liu et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Liu, Xiaoying Taylor, Sarah A. Gromer, Kyle D. Zhang, Danny Hubchak, Susan C. LeCuyer, Brian E. Iwawaki, Takao Shi, Zengdun Rockey, Don C. Green, Richard M. Mechanisms of liver injury in high fat sugar diet fed mice that lack hepatocyte X-box binding protein 1 |
title | Mechanisms of liver injury in high fat sugar diet fed mice that lack hepatocyte X-box binding protein 1 |
title_full | Mechanisms of liver injury in high fat sugar diet fed mice that lack hepatocyte X-box binding protein 1 |
title_fullStr | Mechanisms of liver injury in high fat sugar diet fed mice that lack hepatocyte X-box binding protein 1 |
title_full_unstemmed | Mechanisms of liver injury in high fat sugar diet fed mice that lack hepatocyte X-box binding protein 1 |
title_short | Mechanisms of liver injury in high fat sugar diet fed mice that lack hepatocyte X-box binding protein 1 |
title_sort | mechanisms of liver injury in high fat sugar diet fed mice that lack hepatocyte x-box binding protein 1 |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8759640/ https://www.ncbi.nlm.nih.gov/pubmed/35030194 http://dx.doi.org/10.1371/journal.pone.0261789 |
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