ArticleHepatology (Baltimore, Md.)2016
Carboxylesterase 2 prevents liver steatosis by modulating lipolysis, endoplasmic reticulum stress, and lipogenesis and is regulated by hepatocyte nuclear factor 4 alpha in mice.
Article in Hepatology (Baltimore, Md.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed, 135 citations in OpenAlex.
- Endurance exercise elicits a hepatic memory associated with improved metabolic function and protein secretion.Molecular metabolism · 2026Article
- Genetic or pharmacological inhibition of hepatic TMEM141 attenuates MASH and fibrosis via the ROS-HNF4α signaling pathway.Nature communications · 2026Article
- Oridonin exerts dual therapeutic effects in MASLD mice by integrating lipid homeostasis and drug bioactivation via the LXRα-CES1/CES2 pathway.Acta pharmacologica Sinica · 2026Article
- The regulatory role and mechanism of energy metabolism and immune response in head and neck cancer.Genes & diseases · 2025Review
- Developmental low-dose bisphenol A exposure leads to extensive transcriptome female masculinization and male feminization later in life.Communications medicine · 2025Article
- Mechanistic insights into human carboxylesterase 2 (CES2) inhibition by the CES1 prodrug substrate remdesivir.Drug metabolism and disposition: the biological fate of chemicals · 2025Article
- Orphan Nuclear Receptors in Metabolic Dysfunction-associated Steatotic Liver Disease Development.Journal of clinical and translational hepatology · 2025Review
- Differential expression of capecitabine-related metabolic enzymes in hepatocellular carcinoma and its clinical value: a retrospective cohort study.Discover oncology · 2025Article
- Intestinal human carboxylesterase 2 (CES2) expression rescues drug metabolism and most metabolic syndrome phenotypes in global Ces2 cluster knockout mice.Acta pharmacologica Sinica · 2025Article
- Wet pulverization combined with temperature cycling strategy for extraction ofFood chemistry: X · 2025Article
- Unlocking Therapeutic Potential: Camphorquinone's Role in Alleviating Non-Alcoholic Fatty Liver Disease via SIRT1/LKB1/AMPK Pathway Activation.Tissue engineering and regenerative medicine · 2025Article
- Structure-based identification of HNF4α agonists: Rosmarinic acid as a promising candidate for NAFLD treatment.Computational and structural biotechnology journal · 2025Article
- Spatial Transcriptomic Study Reveals Heterogeneous Metabolic Adaptation and a Role of Pericentral PPARα/CAR/Ces2a Axis During Fasting in Mouse Liver.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Liver matrin-3 protects mice against hepatic steatosis and stress response via constitutive androstane receptor.Molecular metabolism · 2024Article
- Krüppel-like factor 10 protects against metabolic dysfunction-associated steatohepatitis by regulating HNF4α-mediated metabolic pathways.Metabolism: clinical and experimental · 2024Article
- Exerkines and cardiometabolic benefits of exercise: from bench to clinic.EMBO molecular medicine · 2024Review
- SPINK1 Overexpression Correlates with Hepatocellular Carcinoma Treatment Resistance Revealed by Single Cell RNA-Sequencing and Spatial Transcriptomics.Biomolecules · 2024Article
- HNF4α ubiquitination mediated by Peli1 impairs FAO and accelerates pressure overload-induced myocardial hypertrophy.Cell death & disease · 2024Article
- Acanthopanax senticosus ameliorates steatohepatitis through HNF4 alpha pathway activation in mice.Scientific reports · 2024Article
- Transcriptomic analysis of yakAnimal biotechnology · 2023Article
8 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
unlabelledNonalcoholic fatty liver disease (NAFLD) is a common liver disease that ranges from simple steatosis to nonalcoholic steatohepatitis (NASH). So far, the underlying mechanism remains poorly understood. Here, we show that hepatic carboxylesterase 2 (CES2) is markedly reduced in NASH patients, diabetic db/db mice, and high-fat diet (HFD)-fed mice. Restoration of hepatic CES2 expression in db/db or HFD-fed mice markedly ameliorates liver steatosis and insulin resistance. In contrast, knockdown of hepatic CES2 causes liver steatosis and damage in chow- or Western diet-fed C57BL/6 mice. Mechanistically, we demonstrate that CES2 has triglyceride hydrolase activity. As a result, gain of hepatic CES2 function increases fatty acid oxidation and inhibits lipogenesis, whereas loss of hepatic CES2 stimulates lipogenesis by inducing endoplasmic reticulum stress. We further show that loss of hepatic CES2 stimulates lipogenesis in a sterol regulatory element-binding protein 1 (SREBP-1)-dependent manner. Finally, we show that hepatocyte nuclear factor 4 alpha (HNF-4α) plays a key role in controlling hepatic CES2 expression in diabetes, obesity, or NASH.
conclusionCES2 plays a protective role in development of NAFLD. Targeting the HNF-4α/CES2 pathway may be useful for treatment of NAFLD. (Hepatology 2016;63:1860-1874).
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.