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FoxO1 is a critical regulator of hepatocyte lipid deposition in chronic stress mice

Forkhead box O1 (FoxO1) is involved in lipid metabolisms. However, its role in chronic stress-related nonalcoholic fatty liver disease (NAFLD) is unclear. The scientific premise of our study was based on the finding that FoxO1 expression is increased in the liver of mice after chronic stress. It is...

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Autores principales: Liu, Yun-zi, Peng, Wei, Chen, Ji-kuai, Su, Wen-jun, Yan, Wen-jie, Wang, Yun-xia, Jiang, Chun-lei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: PeerJ Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6768057/
https://www.ncbi.nlm.nih.gov/pubmed/31579588
http://dx.doi.org/10.7717/peerj.7668
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author Liu, Yun-zi
Peng, Wei
Chen, Ji-kuai
Su, Wen-jun
Yan, Wen-jie
Wang, Yun-xia
Jiang, Chun-lei
author_facet Liu, Yun-zi
Peng, Wei
Chen, Ji-kuai
Su, Wen-jun
Yan, Wen-jie
Wang, Yun-xia
Jiang, Chun-lei
author_sort Liu, Yun-zi
collection PubMed
description Forkhead box O1 (FoxO1) is involved in lipid metabolisms. However, its role in chronic stress-related nonalcoholic fatty liver disease (NAFLD) is unclear. The scientific premise of our study was based on the finding that FoxO1 expression is increased in the liver of mice after chronic stress. It is important to understand the mechanisms involved in the activation of FoxO1 and how its function affects the liver lipid deposition. We employed a murine chronic stress model, in which mice were treated by plantar electrical stimulation and restraint for 6 weeks, and a cellular model, in which Hepa1–6 cells were treated with corticosterone. We also used a pharmacologic approach as1842856, a highly specific FoxO1 inhibitor. Lipid metabolism related genes levels were measured by qRT-PCR and the lipid levels by biochemical detection. We show that the level of FoxO1 is significantly elevated in the liver of chronic stress mice. Transcription factor FoxO1 regulates a lipid synthesis phenotype of hepatocyte that is involved in the development and progression of NAFLD. We have shown that inhibition of FoxO1 induced phenotypic conversion of hepatocytes and down-regulates lipid synthesis genes expression by hepatocytes, which contribute to lipid deposition in NAFLD. At the cellular level, the inhibitor of FoxO1 as1842856 can also attenuate the lipid deposition of Hepa1–6 cells induced by corticosterone. Targeting FoxO1 is a novel therapeutic target for chronic stress-related NAFLD.
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spelling pubmed-67680572019-10-02 FoxO1 is a critical regulator of hepatocyte lipid deposition in chronic stress mice Liu, Yun-zi Peng, Wei Chen, Ji-kuai Su, Wen-jun Yan, Wen-jie Wang, Yun-xia Jiang, Chun-lei PeerJ Diabetes and Endocrinology Forkhead box O1 (FoxO1) is involved in lipid metabolisms. However, its role in chronic stress-related nonalcoholic fatty liver disease (NAFLD) is unclear. The scientific premise of our study was based on the finding that FoxO1 expression is increased in the liver of mice after chronic stress. It is important to understand the mechanisms involved in the activation of FoxO1 and how its function affects the liver lipid deposition. We employed a murine chronic stress model, in which mice were treated by plantar electrical stimulation and restraint for 6 weeks, and a cellular model, in which Hepa1–6 cells were treated with corticosterone. We also used a pharmacologic approach as1842856, a highly specific FoxO1 inhibitor. Lipid metabolism related genes levels were measured by qRT-PCR and the lipid levels by biochemical detection. We show that the level of FoxO1 is significantly elevated in the liver of chronic stress mice. Transcription factor FoxO1 regulates a lipid synthesis phenotype of hepatocyte that is involved in the development and progression of NAFLD. We have shown that inhibition of FoxO1 induced phenotypic conversion of hepatocytes and down-regulates lipid synthesis genes expression by hepatocytes, which contribute to lipid deposition in NAFLD. At the cellular level, the inhibitor of FoxO1 as1842856 can also attenuate the lipid deposition of Hepa1–6 cells induced by corticosterone. Targeting FoxO1 is a novel therapeutic target for chronic stress-related NAFLD. PeerJ Inc. 2019-09-27 /pmc/articles/PMC6768057/ /pubmed/31579588 http://dx.doi.org/10.7717/peerj.7668 Text en © 2019 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, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited.
spellingShingle Diabetes and Endocrinology
Liu, Yun-zi
Peng, Wei
Chen, Ji-kuai
Su, Wen-jun
Yan, Wen-jie
Wang, Yun-xia
Jiang, Chun-lei
FoxO1 is a critical regulator of hepatocyte lipid deposition in chronic stress mice
title FoxO1 is a critical regulator of hepatocyte lipid deposition in chronic stress mice
title_full FoxO1 is a critical regulator of hepatocyte lipid deposition in chronic stress mice
title_fullStr FoxO1 is a critical regulator of hepatocyte lipid deposition in chronic stress mice
title_full_unstemmed FoxO1 is a critical regulator of hepatocyte lipid deposition in chronic stress mice
title_short FoxO1 is a critical regulator of hepatocyte lipid deposition in chronic stress mice
title_sort foxo1 is a critical regulator of hepatocyte lipid deposition in chronic stress mice
topic Diabetes and Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6768057/
https://www.ncbi.nlm.nih.gov/pubmed/31579588
http://dx.doi.org/10.7717/peerj.7668
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