ArticleThe Journal of biological chemistry2017
Sortilin 1 Modulates Hepatic Cholesterol Lipotoxicity in Mice via Functional Interaction with Liver Carboxylesterase 1.
Article in The Journal of biological chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 47 citations in OpenAlex.
- Triazine Thiols Decrease Apolipoprotein B Secretion From Hepatocytes Through Inhibition of Human Carboxylesterase 1.Cellular and molecular gastroenterology and hepatology · 2026Article
- Impaired chaperone-mediated autophagy leads to abnormal SORT1 (sortilin 1) turnover and CES1-dependent triglyceride hydrolysis.Autophagy · 2025Article
- Identification of a Novel NPC1L1 Inhibitor from Danshen and Its Role in Nonalcoholic Fatty Liver Disease.International journal of molecular sciences · 2025Article
- Discovery of a novel homocysteine thiolactone hydrolase and the catalytic activity of its natural variants.Protein science : a publication of the Protein Society · 2024Article
- Propolis Reduces Inflammation and Dyslipidemia Caused by High-Cholesterol Diet in Mice by Lowering ADAM10/17 Activities.Nutrients · 2024Article
- Kupffer-Cell-Targeted Carboxylesterase 1f Knockdown Deteriorates Lipopolysaccharide/D-Galactosamine-Induced Acute Liver Failure Through Regulating Cellular Polarization in Mice.Canadian journal of gastroenterology & hepatology · 2024Article
- Transcriptomic (DNA Microarray) and Metabolome (LC-TOF-MS) Analyses of the Liver in High-Fat Diet Mice after Intranasal Administration of GALP (Galanin-like Peptide).International journal of molecular sciences · 2023Article
- Transcriptional Regulation of Carboxylesterase 1 in Human Liver: Role of the Nuclear Receptor Subfamily 1 Group H Member 3 and Its Splice Isoforms.Drug metabolism and disposition: the biological fate of chemicals · 2022Article
- Oxidized low-density lipoprotein activates extracellular signal-regulated kinase signaling to downregulate sortilin expression in liver sinusoidal endothelial cells.Journal of gastroenterology and hepatology · 2021Article
- Function of the endolysosomal network in cholesterol homeostasis and metabolic-associated fatty liver disease (MAFLD).Molecular metabolism · 2021Review
- An FGF15/19-TFEB regulatory loop controls hepatic cholesterol and bile acid homeostasis.Nature communications · 2020Article
- Vitamin E Ameliorates Lipid Metabolism in Mice with Nonalcoholic Fatty Liver Disease via Nrf2/CES1 Signaling Pathway.Digestive diseases and sciences · 2019Article
- Hepatocyte sortilin 1 knockout and treatment with a sortilin 1 inhibitor reduced plasma cholesterol in Western diet-fed mice.Journal of lipid research · 2019Article
- Cholesterol and bile acid-mediated regulation of autophagy in fatty liver diseases and atherosclerosis.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2018Review
- Mouse models of gallstone disease.Current opinion in gastroenterology · 2018Review
- Sortilin 1 Loss-of-Function Protects Against Cholestatic Liver Injury by Attenuating Hepatic Bile Acid Accumulation in Bile Duct Ligated Mice.Toxicological sciences : an official journal of the Society of Toxicology · 2018Article
- Sortilin in Glucose Homeostasis: From Accessory Protein to Key Player?Frontiers in pharmacology · 2018Review
- Inhibition of insulin/PI3K/AKT signaling decreases adipose Sortilin 1 in mice and 3T3-L1 adipocytes.Biochimica et biophysica acta. Molecular basis of disease · 2017Article
- Sortilin 1 knockout alters basal adipose glucose metabolism but not diet-induced obesity in mice.FEBS letters · 2017Article
- Structure-Activity Relationships of Pentacyclic Triterpenoids as Potent and Selective Inhibitors against Human Carboxylesterase 1.Frontiers in pharmacology · 2017Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
The liver plays a key role in cholesterol metabolism. Impaired hepatic cholesterol homeostasis causes intracellular free cholesterol accumulation and hepatocyte injury. Sortilin 1 (SORT1) is a lysosomal trafficking receptor that was identified by genome-wide association studies (GWAS) as a novel regulator of cholesterol metabolism in humans. Here we report that SORT1 deficiency protected against cholesterol accumulation-induced liver injury and inflammation in mice. Using an LC-MS/MS-based proteomics approach, we identified liver carboxylesterase 1 (CES1) as a novel SORT1-interacting protein. Mechanistic studies further showed that SORT1 may regulate CES1 lysosomal targeting and degradation and that SORT1 deficiency resulted in higher liver CES1 protein abundance. Previous studies have established an important role of hepatic CES1 in promoting intracellular cholesterol mobilization, cholesterol efflux, and bile acid synthesis. Consistently, high cholesterol atherogenic diet-challenged Sort1 knock-out mice showed less hepatic free cholesterol accumulation, increased bile acid synthesis, decreased biliary cholesterol secretion, and the absence of gallstone formation. SORT1 deficiency did not alter hepatic ceramide and fatty acid metabolism in high cholesterol atherogenic diet-fed mice. Finally, knockdown of liver CES1 in mice markedly increased the susceptibility to high cholesterol diet-induced liver injury and abolished the protective effect against cholesterol lipotoxicity in Sort1 knock-out mice. In summary, this study identified a novel SORT1-CES1 axis that regulates cholesterol-induced liver injury, which provides novel insights that improve our current understanding of the molecular links between SORT1 and cholesterol metabolism. This study further suggests that therapeutic inhibition of SORT1 may be beneficial in improving hepatic cholesterol homeostasis in metabolic and inflammatory liver diseases.
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