ArticleCell metabolism2012
IRE1α-XBP1s induces PDI expression to increase MTP activity for hepatic VLDL assembly and lipid homeostasis.
Article in Cell metabolism, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 127 papers.
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Who cites it
127 citing papers in PubMed.
- The unfolded protein sensor IRE1 is essential for homeostatic dendritic cell maturation.Nature communications · 2026Article
- Review
- Remote regulation of hepatic lipid secretion in the intestine by metabolic interaction of dietary arginine with ornithine.Scientific reports · 2026Article
- FGF1 orchestrates circadian hepatic triglyceride secretion.Nature communications · 2026Article
- TRMT6/TRMT61A-mediated tRNA mCellular & molecular biology letters · 2026Article
- FGF1 ameliorates hepatic steatosis through acute activation of the unfolded protein response and VLDL production.JHEP reports : innovation in hepatology · 2026Article
- Cartilage Intermediate Layer Protein 2 Aggravates Hepatic Lipid Accumulation and Inflammation Through the IRE1α/XBP1 Pathway.International journal of molecular sciences · 2026Article
- Overlapping Yet Distinct Functions of Vacuole Membrane Protein 1 and Transmembrane Protein 41B in Modulating Hepatic Lipoprotein Secretion and Autophagy.Cellular and molecular gastroenterology and hepatology · 2026Article
- Targeting the ER stress sensor IRE1 protects the liver from fibrosis through the downregulation of the proteostasis factor P4HB/PDIA1.Hepatology (Baltimore, Md.) · 2026Article
- Bacteroides uniformis-generated hexadecanedioic acid ameliorates metabolic-associated fatty liver disease.Gut microbes · 2025Article
- Intermodulation of endoplasmic reticulum stress and ferroptosis in diabetic nephropathy: molecular mechanisms and therapeutic potentials.Apoptosis : an international journal on programmed cell death · 2025Review
- Endoplasmic reticulum stress at the forefront of fatty liver diseases and cancer.Pharmacological reviews · 2025Review
- Expanding our understanding of synucleinopathies: proteinopathy, proteinopenia, and lipidopathy.The FEBS journal · 2025Review
- Ceramide mediates cell-to-cell ER stress transmission by modulating membrane fluidity.The Journal of cell biology · 2025Article
- Article
- Unfolded protein responses: Dynamic machinery in wound healing.Pharmacology & therapeutics · 2025Review
- Differential transport pathways of saturated and unsaturated fatty acid esters in male mouse hepatocytes.Nature communications · 2025Article
- Article
- Endoplasmic Reticulum Stress in Cancer Progression: A Comprehensive Review of Its Role and Mechanisms.International journal of medical sciences · 2025Review
- Roles of X-box binding protein 1 in liver pathogenesis.Clinical and molecular hepatology · 2025Review
67 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors.
Funding
Abstract
The unfolded protein response (UPR) is a signaling pathway required to maintain endoplasmic reticulum (ER) homeostasis and hepatic lipid metabolism. Here, we identify an essential role for the inositol-requiring transmembrane kinase/endoribonuclease 1α (IRE1α)-X box binding protein 1 (XBP1) arm of the UPR in regulation of hepatic very low-density lipoprotein (VLDL) assembly and secretion. Hepatocyte-specific deletion of Ire1α reduces lipid partitioning into the ER lumen and impairs the assembly of triglyceride (TG)-rich VLDL but does not affect TG synthesis, de novo lipogenesis, or the synthesis or secretion of apolipoprotein B (apoB). The defect in VLDL assembly is, at least in part, due to decreased microsomal triglyceride-transfer protein (MTP) activity resulting from reduced protein disulfide isomerase (PDI) expression. Collectively, our findings reveal a key role for the IRE1α-XBP1s-PDI axis in linking ER homeostasis with regulation of VLDL production and hepatic lipid homeostasis that may provide a therapeutic target for disorders of lipid metabolism.
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