Premium
Hepatic carboxylesterase 1 is essential for both normal and farnesoid X receptor‐controlled lipid homeostasis
Author(s) -
Xu Jiesi,
Li Yuanyuan,
Chen WeiDong,
Xu Yang,
Yin Liya,
Ge Xuemei,
Jadhav Kavita,
Adorini Luciano,
Zhang Yanqiao
Publication year - 2014
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.26714
Subject(s) - farnesoid x receptor , medicine , endocrinology , lipogenesis , nonalcoholic fatty liver disease , lipid metabolism , glucose homeostasis , homeostasis , cholesterol , chemistry , fatty liver , triglyceride , nuclear receptor , biology , insulin resistance , diabetes mellitus , biochemistry , transcription factor , disease , gene
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. (H epatology 2014;59:1761–1771)