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

ABSTRACT: 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.

SUBMITTER: Liu YZ

PROVIDER: S-EPMC6768057 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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

Liu Yun-Zi YZ Peng Wei W Chen Ji-Kuai JK Su Wen-Jun WJ Yan Wen-Jie WJ Wang Yun-Xia YX Jiang Chun-Lei CL

PeerJ 20190927

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 treate ...[more]

PMID: 31579588

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

Publications

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

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