ArticleThe Journal of clinical investigation2019
Nuclear envelope-localized torsinA-LAP1 complex regulates hepatic VLDL secretion and steatosis.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
39 citing papers in PubMed, 2 syntheses or guidelines pooled it, 68 citations in OpenAlex.
- A common variant that alters SUN1 degradation associates with hepatic steatosis and metabolic traits in multiple cohorts.Journal of hepatology · 2023Pooled it
- Genome-wide association meta-analysis identifies 17 loci associated with nonalcoholic fatty liver disease.Nature genetics · 2023Pooled it
- Hepatic Lipoprotein Production, Cardiometabolic Phenotypes, and Subtypes of Steatotic Liver Disease.Circulation research · 2026Review
- The inner nuclear membrane protein SUN1 regulates cullin-3 neddylation to maintain insulin signaling.bioRxiv : the preprint server for biology · 2026Article
- Article
- Biomarker Discovery for Metabolic Dysfunction-associated Steatotic Liver Disease Utilizing Mendelian Randomization, Machine Learning, and External Validation.Journal of clinical and translational hepatology · 2025Article
- LAP1 Interactome Profiling Provides New Insights into LAP1's Physiological Functions.International journal of molecular sciences · 2024Article
- Quantitative proteome analysis of LAP1-deficient human fibroblasts: A pilot approach for predicting the signaling pathways deregulated in LAP1-associated diseases.Biochemistry and biophysics reports · 2024Article
- TorsinA is essential for neuronal nuclear pore complex localization and maturation.Nature cell biology · 2024Article
- Pla2g12b drives expansion of triglyceride-rich lipoproteins.Nature communications · 2024Article
- Article
- VLDL Biogenesis and Secretion: It Takes a Village.Circulation research · 2024Review
- The Role of Endoplasmic Reticulum in Lipotoxicity during Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) Pathogenesis.The American journal of pathology · 2023Review
- Manganese regulation of COPII condensation controls circulating lipid homeostasis.Nature cell biology · 2023Article
- Hepatocyte-specific loss of LAP2α protects against diet-induced hepatic steatosis, steatohepatitis, and fibrosis in male mice.American journal of physiology. Gastrointestinal and liver physiology · 2023Article
- Cargo Receptor-Mediated ER Export in Lipoprotein Secretion and Lipid Homeostasis.Cold Spring Harbor perspectives in biology · 2023Review
- TorsinA is essential for the timing and localization of neuronal nuclear pore complex biogenesis.bioRxiv : the preprint server for biology · 2023Article
- Review
- DYT-Frontiers in neuroscience · 2023Review
- Hepatocytes Deficient in Nuclear Envelope Protein Lamina-associated Polypeptide 1 are an Ideal Mammalian System to Study Intranuclear Lipid Droplets.Journal of lipid research · 2022Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Deciphering novel pathways regulating liver lipid content has profound implications for understanding the pathophysiology of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Recent evidence suggests that the nuclear envelope is a site of regulation of lipid metabolism but there is limited appreciation of the responsible mechanisms and molecular components within this organelle. We showed that conditional hepatocyte deletion of the inner nuclear membrane protein lamina-associated polypeptide 1 (LAP1) caused defective VLDL secretion and steatosis, including intranuclear lipid accumulation. LAP1 binds to and activates torsinA, an AAA+ ATPase that resides in the perinuclear space and continuous main ER. Deletion of torsinA from mouse hepatocytes caused even greater reductions in VLDL secretion and profound steatosis. Both of these mutant mouse lines developed hepatic steatosis and subsequent steatohepatitis on a regular chow diet in the absence of whole-body insulin resistance or obesity. Our results establish an essential role for the nuclear envelope-localized torsinA-LAP1 complex in hepatic VLDL secretion and suggest that the torsinA pathway participates in the pathophysiology of nonalcoholic fatty liver 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.