ArticleJCI insight2021
Hypomorphic ASGR1 modulates lipid homeostasis via INSIG1-mediated SREBP signaling suppression.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 37 citations in OpenAlex.
- Transcriptome and Experimental Verification Identified Candidate Biomarkers Related to Mitochondrial Metabolism in Sepsis-Associated Encephalopathy.Shock (Augusta, Ga.) · 2026Article
- ASGR1 Deficiency Promotes Liver Fibrosis by Enhancing Pro-Inflammatory Arachidonic Acid Metabolism and ALP Secretion.Immunity, inflammation and disease · 2026Article
- The asialoglycoprotein receptor 1 (ASGR1): emerging new roles in health and disease.Biomarker research · 2026Review
- Insights Into circRNA-Mediated Lipid Metabolism in Cancer Progression.Journal of cellular and molecular medicine · 2026Review
- Single-cell transcriptomics showed that maternal polychlorinated biphenyl exposure dysregulated cell type-specific metabolic responses in the livers of female mouse offsprings.Drug metabolism and disposition: the biological fate of chemicals · 2026Article
- Serum soluble ASGR1 concentration is elevated in patients with metabolic dysfunction-associated steatotic liver disease and is associated with adiponectin.BMJ open diabetes research & care · 2026Article
- Article
- Asialoglycoprotein receptor 1: a multifaceted receptor in the liver and cardiovascular system.Frontiers in medicine · 2025Review
- Serum Soluble Asialoglycoprotein Receptor 1: A Potential Predictor Marker Linked to Type 2 Diabetes Mellitus, Demonstrating Positive Correlation With High Sensitive C-Reactive Protein.Diabetes, metabolic syndrome and obesity : targets and therapy · 2025Article
- Adding a New Piece to the ASGR1 Puzzle: ANGPTL3.Arteriosclerosis, thrombosis, and vascular biology · 2024Article
- ASGR1 Deficiency Inhibits Atherosclerosis in Western Diet-FedArteriosclerosis, thrombosis, and vascular biology · 2024Article
- ASGR1 deficiency improves atherosclerosis but alters liver metabolism in ApoECardiovascular diabetology · 2024Article
- Identification and Analysis of Phenolic Compounds inFoods (Basel, Switzerland) · 2024Article
- Review
- Article
- Deficiency of ASGR1 Alleviates Diet-Induced Systemic Insulin Resistance via Improved Hepatic Insulin Sensitivity.Diabetes & metabolism journal · 2024Article
- Deficiency of ASGR1 promotes liver injury by increasing GP73-mediated hepatic endoplasmic reticulum stress.Nature communications · 2024Article
- Review
- Single-Cell Sequencing and Machine Learning Integration to Identify Candidate Biomarkers in Psoriasis:Journal of inflammation research · 2024Article
- Receptors and Cofactors That Contribute to SARS-CoV-2 Entry: Can Skin Be an Alternative Route of Entry?International journal of molecular sciences · 2023Review
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A population genetic study identified that the asialoglycoprotein receptor 1 (ASGR1) mutation carriers had substantially lower non-HDL-cholesterol (non-HDL-c) levels and reduced risks of cardiovascular diseases. However, the mechanism behind this phenomenon remained unclear. Here, we established Asgr1-knockout mice that represented a plasma lipid profile with significantly lower non-HDL-c and triglyceride (TG) caused by decreased secretion and increased uptake of VLDL/LDL. These 2 phenotypes were linked with the decreased expression of microsomal triglyceride transfer protein and proprotein convertase subtilisin/kexin type 9, 2 key targeted genes of sterol regulatory element-binding proteins (SREBPs). Furthermore, there were fewer nuclear SREBPs (nSREBPs) on account of more SREBPs being trapped in endoplasmic reticulum, which was caused by an increased expression of insulin-induced gene 1 (INSIG1), an anchor of SREBPs. Overexpression and gene knockdown interventions, in different models, were conducted to rescue the ASGR1-deficient phenotypes, and we found that INSIG1 knockdown independently reversed the ASGR1-mutated phenotypes with increased serum total cholesterol, LDL-c, TG, and liver cholesterol content accompanied by restored SREBP signaling. ASGR1 rescue experiments reduced INSIG1 and restored the SREBP network defect as manifested by improved apolipoprotein B secretion and reduced LDL uptake. Our observation demonstrated that increased INSIG1 is a critical factor responsible for ASGR1 deficiency-associated lipid profile changes and nSREBP suppression. This finding of an ASGR1/INSIG1/SREBP axis regulating lipid hemostasis may provide multiple potential targets for lipid-lowering drug development.
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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.