ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2020
Rspo1/Rspo3-LGR4 signaling inhibits hepatic cholesterol synthesis through the AMPKα-SREBP2 pathway.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 24 citations in OpenAlex.
- Endothelial cell LGR4 maintains liver sinusoidal endothelial cell Identity and protects against hepatic steatosis.Life sciences · 2026Article
- Myeloid Cell-Specific Deletion of LGR4 Suppresses Atherosclerotic Lesion Formation.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- AURKA-mediated destabilization of SAPS3 drives ferroptosis evasion via 7-dehydrocholesterol biosynthesis in colorectal cancer.Cell death & disease · 2026Article
- Cholesterol Overload Drives Hepatic Steatosis by Inhibiting OGT-dependent PPARα O-GlcNAcylation and Transactivation.International journal of biological sciences · 2026Article
- Hepatic LGR4 aggravates cholestasis-induced liver injury in mice.American journal of physiology. Gastrointestinal and liver physiology · 2024Article
- The aminosteroid U73122 promotes oligodendrocytes generation and myelin formation.Acta pharmacologica Sinica · 2024Article
- Polyoxometalates Ameliorate Metabolic Dysfunction-Associated Steatotic Liver Disease by Activating the AMPK Signaling Pathway.International journal of nanomedicine · 2024Article
- LGR4 attenuates MGP expression and suppresses EGFR activation-induced triple-negative breast cancer metastasis.American journal of cancer research · 2024Article
- LGR4: A New Receptor Member in Endocrine and Metabolic Diseases.Endocrine reviews · 2023Review
- Mulberry Leaf (Nutrients · 2022Article
- Cistanche tubulosa phenylethanoid glycosides suppressed adipogenesis in 3T3-L1 adipocytes and improved obesity and insulin resistance in high-fat diet induced obese mice.BMC complementary medicine and therapies · 2022Article
- RSPO3 is a novel contraction-inducible factor identified in an "in vitro exercise model" using primary human myotubes.Scientific reports · 2022Article
- Intracellular Cholesterol Synthesis and Transport.Frontiers in cell and developmental biology · 2022Review
- Neochlorogenic Acid Attenuates Hepatic Lipid Accumulation and Inflammation via Regulating miR-34a In Vitro.International journal of molecular sciences · 2021Article
- The Role of LGR4 (GPR48) in Normal and Cancer Processes.International journal of molecular sciences · 2021Review
- Emerging Roles for LGR4 in Organ Development, Energy Metabolism and Carcinogenesis.Frontiers in genetics · 2021Review
- Maprotiline Suppresses Cholesterol Biosynthesis and Hepatocellular Carcinoma Progression Through Direct Targeting of CRABP1.Frontiers in pharmacology · 2021Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 3 countries.
Funding
Abstract
R-spondins (Rspos) are endogenous ligands of leucine-rich repeat-containing G-protein-coupled receptor 4 (LGR4). Rspos-LGR4 signaling plays important roles in embryogenesis, gastrointestinal homeostasis, and food intake. Here, we investigated the impacts of Rspos-LGR4 on hepatic cholesterol synthesis. Rspo1/3 and Lgr4 knockdown mice were used to investigate the impacts of Rspo1/3-LGR4 on hepatic cholesterol synthesis. AMPKα agonist, antagonist, and shRNA were used to explore the downstream targets of Rspos-LGR4 signaling. In our study, we reported that LGR4, Rspo1, and Rspo3 were highly expressed in hepatocytes and their expressions were sensitive to energy states. Rspo1 and Rspo3 reversed OA-induced cholesterol synthesis, accompanying with increased the phosphorylation of AMPKα Thr172, reduced SREBP2 nuclear translocation, and Srebf2 mRNA expression. Conversely, hepatic LGR4 knockdown increased hepatic cholesterol synthesis and decreased the phosphorylation of AMPKα both in vitro and in vivo. Activation or inhibition of AMPKα significantly abolished the effects of LGR4 deficiency or Rspos, respectively, on cholesterol synthesis. Knockdown of AMPKα1 or/and AMPKα2 repressed Rspos-induced inhibition on cholesterol synthesis. Our study indicates that Rspo1/Rspo3-LGR4 signaling in hepatocytes suppresses cholesterol synthesis via the AMPKα-SREBP2 pathway.
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Registered trials
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