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Hepatic damage caused by long-term high cholesterol intake induces a dysfunctional restorative macrophage population in experimental NASH

Excessive dietary cholesterol is preferentially stored in the liver, favoring the development of nonalcoholic steatohepatitis (NASH), characterized by progressive hepatic inflammation and fibrosis. Emerging evidence indicates a critical contribution of hepatic macrophages to NASH severity. However,...

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Autores principales: Maretti-Mira, Ana C., Salomon, Matthew P., Hsu, Angela M., Kanel, Gary C., Golden-Mason, Lucy
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9495937/
https://www.ncbi.nlm.nih.gov/pubmed/36159810
http://dx.doi.org/10.3389/fimmu.2022.968366
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author Maretti-Mira, Ana C.
Salomon, Matthew P.
Hsu, Angela M.
Kanel, Gary C.
Golden-Mason, Lucy
author_facet Maretti-Mira, Ana C.
Salomon, Matthew P.
Hsu, Angela M.
Kanel, Gary C.
Golden-Mason, Lucy
author_sort Maretti-Mira, Ana C.
collection PubMed
description Excessive dietary cholesterol is preferentially stored in the liver, favoring the development of nonalcoholic steatohepatitis (NASH), characterized by progressive hepatic inflammation and fibrosis. Emerging evidence indicates a critical contribution of hepatic macrophages to NASH severity. However, the impact of cholesterol on these cells in the setting of NASH remains elusive. Here, we demonstrate that the dietary cholesterol content directly affects hepatic macrophage global gene expression. Our findings suggest that the modifications triggered by prolonged high cholesterol intake induce long-lasting hepatic damage and support the expansion of a dysfunctional pro-fibrotic restorative macrophage population even after cholesterol reduction. The present work expands the understanding of the modulatory effects of cholesterol on innate immune cell transcriptome and may help identify novel therapeutic targets for NASH intervention.
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spelling pubmed-94959372022-09-23 Hepatic damage caused by long-term high cholesterol intake induces a dysfunctional restorative macrophage population in experimental NASH Maretti-Mira, Ana C. Salomon, Matthew P. Hsu, Angela M. Kanel, Gary C. Golden-Mason, Lucy Front Immunol Immunology Excessive dietary cholesterol is preferentially stored in the liver, favoring the development of nonalcoholic steatohepatitis (NASH), characterized by progressive hepatic inflammation and fibrosis. Emerging evidence indicates a critical contribution of hepatic macrophages to NASH severity. However, the impact of cholesterol on these cells in the setting of NASH remains elusive. Here, we demonstrate that the dietary cholesterol content directly affects hepatic macrophage global gene expression. Our findings suggest that the modifications triggered by prolonged high cholesterol intake induce long-lasting hepatic damage and support the expansion of a dysfunctional pro-fibrotic restorative macrophage population even after cholesterol reduction. The present work expands the understanding of the modulatory effects of cholesterol on innate immune cell transcriptome and may help identify novel therapeutic targets for NASH intervention. Frontiers Media S.A. 2022-09-08 /pmc/articles/PMC9495937/ /pubmed/36159810 http://dx.doi.org/10.3389/fimmu.2022.968366 Text en Copyright © 2022 Maretti-Mira, Salomon, Hsu, Kanel and Golden-Mason https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Maretti-Mira, Ana C.
Salomon, Matthew P.
Hsu, Angela M.
Kanel, Gary C.
Golden-Mason, Lucy
Hepatic damage caused by long-term high cholesterol intake induces a dysfunctional restorative macrophage population in experimental NASH
title Hepatic damage caused by long-term high cholesterol intake induces a dysfunctional restorative macrophage population in experimental NASH
title_full Hepatic damage caused by long-term high cholesterol intake induces a dysfunctional restorative macrophage population in experimental NASH
title_fullStr Hepatic damage caused by long-term high cholesterol intake induces a dysfunctional restorative macrophage population in experimental NASH
title_full_unstemmed Hepatic damage caused by long-term high cholesterol intake induces a dysfunctional restorative macrophage population in experimental NASH
title_short Hepatic damage caused by long-term high cholesterol intake induces a dysfunctional restorative macrophage population in experimental NASH
title_sort hepatic damage caused by long-term high cholesterol intake induces a dysfunctional restorative macrophage population in experimental nash
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9495937/
https://www.ncbi.nlm.nih.gov/pubmed/36159810
http://dx.doi.org/10.3389/fimmu.2022.968366
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