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

Jiesi Xu1, Yuanyuan Li1, Wei-Dong Chen1,2

  • 1Department of Integrative Medical Sciences, Northeast Ohio Medical University, Rootstown, OH 44272, USA.

Hepatology (Baltimore, Md.)
|September 17, 2013
PubMed
Abstract

Insights

Hepatic carboxylesterase 1 (CES1) regulates lipid and glucose levels. Activating Farnesoid X receptor (FXR) lowers triglycerides by increasing CES1, offering a potential NAFLD treatment strategy.

Area of Science:

  • Hepatology
  • Metabolic Diseases
  • Molecular Biology

Background:

  • Nonalcoholic fatty liver disease (NAFLD) is a global health issue.
  • Farnesoid X receptor (FXR) is a potential therapeutic target for NAFLD.
  • The precise mechanism by which FXR activation reduces hepatic triglyceride (TG) levels is not fully understood.

Purpose of the Study:

  • To investigate the role of hepatic carboxylesterase 1 (CES1) in lipid homeostasis.
  • To elucidate the relationship between FXR activation and CES1 in regulating lipid metabolism.

Main Methods:

  • Overexpression and knockdown of hepatic CES1 in wild-type and diabetic mice.
  • Measurement of hepatic triglyceride, plasma glucose, and plasma cholesterol levels.
  • Investigation of FXR-induced changes in CES1 expression and its downstream effects.

Main Results:

  • Overexpression of hepatic CES1 reduced hepatic TG and plasma glucose.
  • Knockdown of hepatic CES1 increased hepatic TG and plasma cholesterol.
  • FXR activation upregulated hepatic CES1, leading to decreased hepatic and plasma TG and plasma cholesterol in a CES1-dependent manner.

Conclusions:

  • Hepatic CES1 is crucial for regulating lipid and carbohydrate metabolism.
  • CES1 plays a key role in FXR-mediated lipid homeostasis.
  • CES1's TG hydrolase activity influences fatty acid oxidation and de novo lipogenesis.

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