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Lipid balance must be just right to prevent development of severe liver damage

Nonalcoholic fatty liver disease (NAFLD) is a major health concern that often associates with obesity and diabetes. Fatty liver is usually a benign condition, yet a fraction of individuals progress to severe forms of liver damage, including nonalcoholic steatohepatitis (NASH) and hepatocellular carc...

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Autores principales: Osborne, Timothy F., Espenshade, Peter J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Clinical Investigation 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9151688/
https://www.ncbi.nlm.nih.gov/pubmed/35642642
http://dx.doi.org/10.1172/JCI160326
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author Osborne, Timothy F.
Espenshade, Peter J.
author_facet Osborne, Timothy F.
Espenshade, Peter J.
author_sort Osborne, Timothy F.
collection PubMed
description Nonalcoholic fatty liver disease (NAFLD) is a major health concern that often associates with obesity and diabetes. Fatty liver is usually a benign condition, yet a fraction of individuals progress to severe forms of liver damage, including nonalcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC). Elevated sterol regulatory element–binding protein–driven (SREBP-driven) hepatocyte lipid synthesis is associated with NAFLD in humans and mice. In this issue of the JCI, Kawamura, Matsushita, et al. evaluated the role of SREBP-dependent lipid synthesis in the development of NAFLD, NASH, and HCC in the phosphatase and tensin homolog–knockout (PTEN-knockout) NASH model. Deletion of the gene encoding SREBP cleavage–activating protein (SCAP) from the liver resulted in decreased hepatic lipids, as expected. However, SCAP deletion accelerated progression to more severe liver damage, including NASH and HCC. This study provides a note of caution for those pursuing de novo fat biosynthesis as a therapeutic intervention in human NASH.
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spelling pubmed-91516882022-06-02 Lipid balance must be just right to prevent development of severe liver damage Osborne, Timothy F. Espenshade, Peter J. J Clin Invest Commentary Nonalcoholic fatty liver disease (NAFLD) is a major health concern that often associates with obesity and diabetes. Fatty liver is usually a benign condition, yet a fraction of individuals progress to severe forms of liver damage, including nonalcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC). Elevated sterol regulatory element–binding protein–driven (SREBP-driven) hepatocyte lipid synthesis is associated with NAFLD in humans and mice. In this issue of the JCI, Kawamura, Matsushita, et al. evaluated the role of SREBP-dependent lipid synthesis in the development of NAFLD, NASH, and HCC in the phosphatase and tensin homolog–knockout (PTEN-knockout) NASH model. Deletion of the gene encoding SREBP cleavage–activating protein (SCAP) from the liver resulted in decreased hepatic lipids, as expected. However, SCAP deletion accelerated progression to more severe liver damage, including NASH and HCC. This study provides a note of caution for those pursuing de novo fat biosynthesis as a therapeutic intervention in human NASH. American Society for Clinical Investigation 2022-06-01 2022-06-01 /pmc/articles/PMC9151688/ /pubmed/35642642 http://dx.doi.org/10.1172/JCI160326 Text en © 2022 Osborne et al. https://creativecommons.org/licenses/by/4.0/This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Commentary
Osborne, Timothy F.
Espenshade, Peter J.
Lipid balance must be just right to prevent development of severe liver damage
title Lipid balance must be just right to prevent development of severe liver damage
title_full Lipid balance must be just right to prevent development of severe liver damage
title_fullStr Lipid balance must be just right to prevent development of severe liver damage
title_full_unstemmed Lipid balance must be just right to prevent development of severe liver damage
title_short Lipid balance must be just right to prevent development of severe liver damage
title_sort lipid balance must be just right to prevent development of severe liver damage
topic Commentary
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9151688/
https://www.ncbi.nlm.nih.gov/pubmed/35642642
http://dx.doi.org/10.1172/JCI160326
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