ArticleThe Journal of clinical investigation2012
Activation of ER stress and mTORC1 suppresses hepatic sortilin-1 levels in obese mice.
Article in The Journal of clinical investigation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers, 1 of them a synthesis that pooled it.
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Who cites it
65 citing papers in PubMed, 1 synthesis or guideline pooled it, 104 citations in OpenAlex.
- Finding memo: versatile interactions of the VPS10p-Domain receptors in Alzheimer's disease.Molecular neurodegeneration · 2022Pooled it
- The role of sortilin in cardiovascular calcification: mechanisms and therapeutic potential.Frontiers in cardiovascular medicine · 2026Review
- Pathogenic Role of mTOR Signaling in Cardiometabolic Disease: Implications for Heart, Liver, and Kidney Dysfunction.Physiological research · 2025Review
- Role of amino acids in the regulation of hepatic gluconeogenesis and lipogenesis in metabolic dysfunctionassociated steatotic liver disease.Clinical and molecular hepatology · 2025Review
- The role of inflammation induced by necroptosis in the development of fibrosis and liver cancer in novel knockin mouse models fed a western diet.GeroScience · 2025Article
- Impaired chaperone-mediated autophagy leads to abnormal SORT1 (sortilin 1) turnover and CES1-dependent triglyceride hydrolysis.Autophagy · 2025Article
- Pro-renin Receptor (PRR) as a Target to Reduce Non-alcoholic Fatty Liver Disease Post Liver Transplantation.Current medicinal chemistry · 2025Review
- Evaluating SORT1 and SESN1 genes expression in peripheral blood mononuclear cells and oxidative stress status in patients with coronary artery disease.BMC genomic data · 2024Article
- Insulin Regulation of Hepatic Lipid Homeostasis.Comprehensive Physiology · 2023Review
- Metabolic Injury of Hepatocytes Promotes Progression of NAFLD and AALD.Seminars in liver disease · 2022Review
- Emerging roles of sortilin in affecting the metabolism of glucose and lipid profiles.Bosnian journal of basic medical sciences · 2022Review
- Sortilin restricts secretion of apolipoprotein B-100 by hepatocytes under stressed but not basal conditions.The Journal of clinical investigation · 2022Article
- Activation of Liver mTORC1 Protects Against NASH via Dual Regulation of VLDL-TAG Secretion and De Novo Lipogenesis.Cellular and molecular gastroenterology and hepatology · 2022Article
- Multi-organ Coordination of Lipoprotein Secretion by Hormones, Nutrients and Neural Networks.Endocrine reviews · 2021Review
- Overexpression of sortilin is associated with 5-FU resistance and poor prognosis in colorectal cancer.Journal of cellular and molecular medicine · 2021Article
- Lipoprotein A, combined with alanine aminotransferase and aspartate aminotransferase, contributes to predicting the occurrence of NASH: a cross-sectional study.Lipids in health and disease · 2020Article
- Activation of microRNA-378a-3p biogenesis promotes hepatic secretion of VLDL and hyperlipidemia by modulating ApoB100-Sortilin1 axis.Theranostics · 2020Article
- Article
- Genetics-driven discovery of novel regulators of lipid metabolism.Current opinion in lipidology · 2019Review
- Novel elucidation and treatment of pancreatic chronic graft-versus-host disease in mice.Royal Society open science · 2018Article
5 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 3 institutions in 1 country.
Funding
Abstract
Recent GWAS have identified SNPs at a human chromosom1 locus associated with coronary artery disease risk and LDL cholesterol levels. The SNPs are also associated with altered expression of hepatic sortilin-1 (SORT1), which encodes a protein thought to be involved in apoB trafficking and degradation. Here, we investigated the regulation of Sort1 expression in mouse models of obesity. Sort1 expression was markedly repressed in both genetic (ob/ob) and high-fat diet models of obesity; restoration of hepatic sortilin-1 levels resulted in reduced triglyceride and apoB secretion. Mouse models of obesity also exhibit increased hepatic activity of mammalian target of rapamycin complex 1 (mTORC1) and ER stress, and we found that administration of the mTOR inhibitor rapamycin to ob/ob mice reduced ER stress and increased hepatic sortilin-1 levels. Conversely, genetically increased hepatic mTORC1 activity was associated with repressed Sort1 and increased apoB secretion. Treating WT mice with the ER stressor tunicamycin led to marked repression of hepatic sortilin-1 expression, while administration of the chemical chaperone PBA to ob/ob mice led to amelioration of ER stress, increased sortilin-1 expression, and reduced apoB and triglyceride secretion. Moreover, the ER stress target Atf3 acted at the SORT1 promoter region as a transcriptional repressor, whereas knockdown of Atf3 mRNA in ob/ob mice led to increased hepatic sortilin-1 levels and decreased apoB and triglyceride secretion. Thus, in mouse models of obesity, induction of mTORC1 and ER stress led to repression of hepatic Sort1 and increased VLDL secretion via Atf3. This pathway may contribute to dyslipidemia in metabolic disease.
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Registered trials
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.