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Fat causes necrosis and inflammation in parenchymal cells in human steatotic liver

Adapted fixation methods for electron microscopy allowed us to study liver cell fine structure in 217 biopsies of intact human livers over the course of 10 years. The following novel observations and concepts arose: single fat droplets in parenchymal cells can grow to a volume four times larger than...

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Autores principales: Wisse, Eddie, Braet, Filip, Shami, Gerald J., Zapotoczny, Bartlomiej, Vreuls, Celien, Verhaegh, Pauline, Frederik, Peter, Peters, Peters J., Olde Damink, Steven, Koek, Ger
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8755686/
https://www.ncbi.nlm.nih.gov/pubmed/34524512
http://dx.doi.org/10.1007/s00418-021-02030-8
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author Wisse, Eddie
Braet, Filip
Shami, Gerald J.
Zapotoczny, Bartlomiej
Vreuls, Celien
Verhaegh, Pauline
Frederik, Peter
Peters, Peters J.
Olde Damink, Steven
Koek, Ger
author_facet Wisse, Eddie
Braet, Filip
Shami, Gerald J.
Zapotoczny, Bartlomiej
Vreuls, Celien
Verhaegh, Pauline
Frederik, Peter
Peters, Peters J.
Olde Damink, Steven
Koek, Ger
author_sort Wisse, Eddie
collection PubMed
description Adapted fixation methods for electron microscopy allowed us to study liver cell fine structure in 217 biopsies of intact human livers over the course of 10 years. The following novel observations and concepts arose: single fat droplets in parenchymal cells can grow to a volume four times larger than the original cell, thereby extremely marginalizing the cytoplasm with all organelles. Necrosis of single parenchymal cells, still containing one huge fat droplet, suggests death by fat in a process of single-cell steatonecrosis. In a later stage of single-cell steatonecrosis, neutrophils and erythrocytes surround the single fat droplet, forming an inflammatory fat follicle indicating the apparent onset of inflammation. Also, fat droplets frequently incorporate masses of filamentous fragments and other material, most probably representing Mallory substance. No other structure or material was found that could possibly represent Mallory bodies. We regularly observe the extrusion of huge fat droplets, traversing the peripheral cytoplasm of parenchymal cells, the Disse space and the endothelium. These fat droplets fill the sinusoid as a sinusoidal lipid embolus. In conclusion, adapted methods of fixation applied to human liver tissue revealed that single, huge fat droplets cause necrosis and inflammation in single parenchymal cells. Fat droplets also collect Mallory substance and give rise to sinusoidal fat emboli. Therefore, degreasing of the liver seems to be an essential therapeutic first step in the self-repairing of non-alcoholic fatty liver disease. This might directly reduce single-cell steatotic necrosis and inflammation as elements in non-alcoholic steatohepatitis progression. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00418-021-02030-8.
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spelling pubmed-87556862022-01-20 Fat causes necrosis and inflammation in parenchymal cells in human steatotic liver Wisse, Eddie Braet, Filip Shami, Gerald J. Zapotoczny, Bartlomiej Vreuls, Celien Verhaegh, Pauline Frederik, Peter Peters, Peters J. Olde Damink, Steven Koek, Ger Histochem Cell Biol Original Paper Adapted fixation methods for electron microscopy allowed us to study liver cell fine structure in 217 biopsies of intact human livers over the course of 10 years. The following novel observations and concepts arose: single fat droplets in parenchymal cells can grow to a volume four times larger than the original cell, thereby extremely marginalizing the cytoplasm with all organelles. Necrosis of single parenchymal cells, still containing one huge fat droplet, suggests death by fat in a process of single-cell steatonecrosis. In a later stage of single-cell steatonecrosis, neutrophils and erythrocytes surround the single fat droplet, forming an inflammatory fat follicle indicating the apparent onset of inflammation. Also, fat droplets frequently incorporate masses of filamentous fragments and other material, most probably representing Mallory substance. No other structure or material was found that could possibly represent Mallory bodies. We regularly observe the extrusion of huge fat droplets, traversing the peripheral cytoplasm of parenchymal cells, the Disse space and the endothelium. These fat droplets fill the sinusoid as a sinusoidal lipid embolus. In conclusion, adapted methods of fixation applied to human liver tissue revealed that single, huge fat droplets cause necrosis and inflammation in single parenchymal cells. Fat droplets also collect Mallory substance and give rise to sinusoidal fat emboli. Therefore, degreasing of the liver seems to be an essential therapeutic first step in the self-repairing of non-alcoholic fatty liver disease. This might directly reduce single-cell steatotic necrosis and inflammation as elements in non-alcoholic steatohepatitis progression. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00418-021-02030-8. Springer Berlin Heidelberg 2021-09-15 2022 /pmc/articles/PMC8755686/ /pubmed/34524512 http://dx.doi.org/10.1007/s00418-021-02030-8 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis 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 Original Paper
Wisse, Eddie
Braet, Filip
Shami, Gerald J.
Zapotoczny, Bartlomiej
Vreuls, Celien
Verhaegh, Pauline
Frederik, Peter
Peters, Peters J.
Olde Damink, Steven
Koek, Ger
Fat causes necrosis and inflammation in parenchymal cells in human steatotic liver
title Fat causes necrosis and inflammation in parenchymal cells in human steatotic liver
title_full Fat causes necrosis and inflammation in parenchymal cells in human steatotic liver
title_fullStr Fat causes necrosis and inflammation in parenchymal cells in human steatotic liver
title_full_unstemmed Fat causes necrosis and inflammation in parenchymal cells in human steatotic liver
title_short Fat causes necrosis and inflammation in parenchymal cells in human steatotic liver
title_sort fat causes necrosis and inflammation in parenchymal cells in human steatotic liver
topic Original Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8755686/
https://www.ncbi.nlm.nih.gov/pubmed/34524512
http://dx.doi.org/10.1007/s00418-021-02030-8
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