ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2021
Hepatocyte-specific expression of human carboxylesterase 2 attenuates nonalcoholic steatohepatitis in mice.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 23 citations in OpenAlex.
- Mechanistic insights into human carboxylesterase 2 (CES2) inhibition by the CES1 prodrug substrate remdesivir.Drug metabolism and disposition: the biological fate of chemicals · 2025Article
- The diagnostic value of hydroxyproline combined with tuberculosis infection T lymphocyte spot assay in pulmonary tuberculosis.Journal of thoracic disease · 2024Article
- Atf3-mediated metabolic reprogramming in hepatic macrophage orchestrates metabolic dysfunction-associated steatohepatitis.Science advances · 2024Article
- Exerkines and cardiometabolic benefits of exercise: from bench to clinic.EMBO molecular medicine · 2024Review
- Acanthopanax senticosus ameliorates steatohepatitis through HNF4 alpha pathway activation in mice.Scientific reports · 2024Article
- Organism-wide, cell-type-specific secretome mapping of exercise training in mice.Cell metabolism · 2023Article
- Palmitate and thapsigargin have contrasting effects on ER membrane lipid composition and ER proteostasis in neuronal cells.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2022Article
- The Crystal Structure of Mouse Ces2c, a Potential Ortholog of Human CES2, Shows Structural Similarities in Substrate Regulation and Product Release to Human CES1.International journal of molecular sciences · 2022Article
- CES2 sustains HNF4α expression to promote pancreatic adenocarcinoma progression through an epoxide hydrolase-dependent regulatory loop.Molecular metabolism · 2022Article
- Combined Use of Bicyclol and Berberine Alleviates Mouse Nonalcoholic Fatty Liver Disease.Frontiers in pharmacology · 2022Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Human carboxylesterase 2 (CES2) has triacylglycerol hydrolase (TGH) activities and plays an important role in lipolysis. In this study, we aim to determine the role of human CES2 in the progression or reversal of steatohepatitis in diet-induced or genetically obese mice. High-fat/high-cholesterol/high-fructose (HFCF) diet-fed C57BL/6 mice or db/db mice were intravenously injected with an adeno-associated virus expressing human CES2 under the control of an albumin promoter. Human CES2 protected against HFCF diet-induced nonalcoholic fatty liver disease (NAFLD) in C57BL/6J mice and reversed steatohepatitis in db/db mice. Human CES2 also improved glucose tolerance and insulin sensitivity. Mechanistically, human CES2 reduced hepatic triglyceride (T) and free fatty acid (FFA) levels by inducing lipolysis and fatty acid oxidation and inhibiting lipogenesis via suppression of sterol regulatory element-binding protein 1. Furthermore, human CES2 overexpression improved mitochondrial respiration and glycolytic function, and inhibited gluconeogenesis, lipid peroxidation, apoptosis, and inflammation. Our data suggest that hepatocyte-specific expression of human CES2 prevents and reverses steatohepatitis. Targeting hepatic CES2 may be an attractive strategy for treatment of NAFLD.
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