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

• Published in: Hepatology (Baltimore, Md.) Vol. 59; no. 5; pp. 1761 - 1771
• Main Authors: Xu, Jiesi, Li, Yuanyuan, Chen, Wei‐Dong, Xu, Yang, Yin, Liya, Ge, Xuemei, Jadhav, Kavita, Adorini, Luciano, Zhang, Yanqiao
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.05.2014
• Subjects: Animals; Carboxylic Ester Hydrolases - physiology; Cholesterol - blood; Fatty Acids - metabolism; Hepatology; Homeostasis; Lipid Metabolism; Lipids; Lipogenesis; Liver - enzymology; Mice; Mice, Inbred C57BL; Receptors, Cytoplasmic and Nuclear - physiology; Rodents; Sterol Regulatory Element Binding Protein 1 - physiology; Triglycerides - metabolism
• ISSN: 0270-9139; 1527-3350
• DOI: 10.1002/hep.26714

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. (Hepatology 2014;59:1761–1771)