ArticleThe Journal of biological chemistry2016
LRP1 Protein Deficiency Exacerbates Palmitate-induced Steatosis and Toxicity in Hepatocytes.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.
- Unraveling the Role of LRP1 in Alzheimer's Disease: A Focus on Aβ Clearance and the Liver-Brain Axis.Journal of molecular neuroscience : MN · 2025Pooled it
- SomaLogic proteomics reveals new biomarkers and provides mechanistic, clinical insights into Acetyl coA Carboxylase (ACC) inhibition in Non-alcoholic Steatohepatitis (NASH).Scientific reports · 2024Trial
- Alveolar type 2 cell LRP1 is needed for surfactant phospholipid metabolism and pulmonary function in mice.Journal of lipid research · 2026Article
- Exploring LRP-1 in the liver-brain axis: implications for Alzheimer's disease.Molecular biology reports · 2025Review
- Skeletal progenitor LRP1 deficiency causes severe and persistent skeletal defects with Wnt pathway dysregulation.Bone research · 2025Article
- LRP1 mitigates intervertebral disc degeneration by inhibiting endoplasmic reticulum stress through stabilizing the PPARγ.Journal of orthopaedic translation · 2025Article
- LRP1 facilitates hepatic glycogenesis by improving the insulin signaling pathway in HFD-fed mice.Animal models and experimental medicine · 2024Article
- Hepatic LRP-1 plays an important role in amyloidosis in Alzheimer's disease mice: Potential role in chronic heavy alcohol feeding.Neurobiology of disease · 2024Article
- Sphingosine kinase 2 and p62 regulation are determinants of sexual dimorphism in hepatocellular carcinoma.Molecular metabolism · 2024Article
- Novel insights into the multifaceted and tissue-specific roles of the endocytic receptor LRP1.The Journal of biological chemistry · 2024Review
- Article
- Hepatic HAX-1 inactivation prevents metabolic diseases by enhancing mitochondrial activity and bile salt export.The Journal of biological chemistry · 2020Article
- Prominent Receptors of Liver Sinusoidal Endothelial Cells in Liver Homeostasis and Disease.Frontiers in physiology · 2020Review
- p53 Regulates the Expression of LRP1 and Apoptosis through a Stress Intensity-Dependent MicroRNA Feedback Loop.Cell reports · 2018Article
- Low-density lipoprotein receptor-related protein-1 dysfunction synergizes with dietary cholesterol to accelerate steatohepatitis progression.The Journal of biological chemistry · 2018Article
- Intracellular lipid metabolism impairs β cell compensation during diet-induced obesity.The Journal of clinical investigation · 2018Article
- Role of the LDL Receptor-Related Protein 1 in Regulating Protease Activity and Signaling Pathways in the Vasculature.Current drug targets · 2018Review
- Hepatic Lipophagy: New Insights into Autophagic Catabolism of Lipid Droplets in the Liver.Hepatology communications · 2017Article
- Hepatic LDL receptor-related protein-1 deficiency alters mitochondrial dynamics through phosphatidylinositol 4,5-bisphosphate reduction.The Journal of biological chemistryArticle
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
LRP1 (LDL receptor-related protein-1) is a ubiquitous receptor with both cell signaling and ligand endocytosis properties. In the liver, LRP1 serves as a chylomicron remnant receptor and also participates in the transport of extracellular cathepsin D to the lysosome for prosaposin activation. The current study showed that in comparison with wild type mice, hepatocyte-specific LRP1 knock-out (hLrp1(-/-)) mice were more susceptible to fasting-induced lipid accumulation in the liver. Primary hepatocytes isolated from hLrp1(-/-) mice also accumulated more intracellular lipids and experienced higher levels of endoplasmic reticulum (ER) stress after palmitate treatment compared with similarly treated hLrp1(+/+) hepatocytes. Palmitate-treated hLrp1(-/-) hepatocytes displayed similar LC3-II levels, but the levels of p62 were elevated in comparison with palmitate-treated hLrp1(+/+) hepatocytes, suggesting that the elevated lipid accumulation in LRP1-defective hepatocytes was not due to defects in autophagosome formation but was due to impairment of lipophagic lipid hydrolysis in the lysosome. Additional studies showed increased palmitate-induced oxidative stress, mitochondrial and lysosomal permeability, and cell death in hLrp1(-/-) hepatocytes. Importantly, the elevated cell death and ER stress observed in hLrp1(-/-) hepatocytes were abrogated by E64D treatment, whereas inhibiting ER stress diminished cell death but not lysosomal permeabilization. Taken together, these results documented that LRP1 deficiency in hepatocytes promotes lipid accumulation and lipotoxicity through lysosomal-mitochondrial permeabilization and ER stress that ultimately result in cell death. Hence, LRP1 dysfunction may be a major risk factor in fatty liver disease progression.
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Registered trials
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