Hepatic carboxylesterase 1 is essential for both normal and farnesoid X receptor-controlled lipid homeostasis.

Title

Hepatic carboxylesterase 1 is essential for both normal and farnesoid X receptor-controlled lipid homeostasis.

Creator

Xu Jiesi; Li Yuanyuan; Chen Wei-Dong; Xu Yang; Yin Liya; Ge Xuemei; Jadhav Kavita; Adorini Luciano; Zhang Yanqiao

Publisher

Hepatology (Baltimore, Md.)

Date

2014
2014-05

Description

UNLABELLED: Nonalcoholic fatty liver disease (NAFLD) is one of the major health concerns worldwide. Farnesoid X receptor (FXR) is considered a therapeutic target for treatment of NAFLD. However, the mechanism by which activation of FXR lowers hepatic triglyceride (TG) levels remains unknown. Here we investigated the role of hepatic carboxylesterase 1 (CES1) in regulating both normal and FXR-controlled lipid homeostasis. Overexpression of hepatic CES1 lowered hepatic TG and plasma glucose levels in both wild-type and diabetic mice. In contrast, knockdown of hepatic CES1 increased hepatic TG and plasma cholesterol levels. These effects likely resulted from the TG hydrolase activity of CES1, with subsequent changes in fatty acid oxidation and/or de novo lipogenesis. Activation of FXR induced hepatic CES1, and reduced the levels of hepatic and plasma TG as well as plasma cholesterol in a CES1-dependent manner. CONCLUSION: Hepatic CES1 plays a critical role in regulating both lipid and carbohydrate metabolism and FXR-controlled lipid homeostasis.

Subject

*Homeostasis; *Lipid Metabolism; Animals; Carboxylic Ester Hydrolases/*physiology; Cholesterol/blood; Cytoplasmic and Nuclear/*physiology; Fatty Acids/metabolism; Inbred C57BL; Lipogenesis; Liver/*enzymology; Mice; Receptors; Sterol Regulatory Element Binding Protein 1/physiology; Triglycerides/metabolism

Identifier

Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Pages

1761–1771

Issue

5

Volume

59

Citation

Xu Jiesi; Li Yuanyuan; Chen Wei-Dong; Xu Yang; Yin Liya; Ge Xuemei; Jadhav Kavita; Adorini Luciano; Zhang Yanqiao, “Hepatic carboxylesterase 1 is essential for both normal and farnesoid X receptor-controlled lipid homeostasis.,” NEOMED Bibliography Database, accessed April 16, 2021, https://neomed.omeka.net/items/show/3013.

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