{"corpus_id":195688640,"paper_sha":"3542838ada2fde3beb0236a4f264b23659d77ecd","doi":"10.1038/nature10111","arxiv_id":null,"pmid":21614002,"pmcid":"3150801","mag_id":2033997896,"dblp_id":null,"acl_id":null,"title":"Antidiabetic actions of a phosphatidylcholine ligand for nuclear receptor LRH-1","year":2011,"publication_date":"2011-05-25","venue":"Nature","journal":{"name":"Nature","pages":"506 - 510","volume":"474"},"journal_issn":null,"journal_title":null,"publication_types":["JournalArticle"],"pubmed_pub_types":["Journal Article","Research Support, N.I.H., Extramural","Research Support, Non-U.S. Gov't","Research Support, U.S. Gov't, Non-P.H.S."],"s2_fields_of_study":["Biology","Medicine","Chemistry"],"reference_count":32,"citation_count":194,"influential_citation_count":11,"is_open_access":false,"arxiv_categories":null,"arxiv_license":null,"arxiv_journal_ref":null,"mesh_headings":[{"d":"Animals","mj":false,"ui":"D000818"},{"d":"Bile Acids and Salts","mj":false,"qs":[{"q":"biosynthesis","mj":false,"ui":"Q000096"},{"q":"metabolism","mj":false,"ui":"Q000378"},{"q":"pharmacology","mj":false,"ui":"Q000494"}],"ui":"D001647"},{"d":"Blood Glucose","mj":false,"qs":[{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D001786"},{"d":"Cell Line","mj":false,"ui":"D002460"},{"d":"Disease Models, Animal","mj":false,"ui":"D004195"},{"d":"Fatty Liver","mj":false,"qs":[{"q":"drug therapy","mj":false,"ui":"Q000188"},{"q":"enzymology","mj":false,"ui":"Q000201"}],"ui":"D005234"},{"d":"HeLa Cells","mj":false,"ui":"D006367"},{"d":"Homeostasis","mj":false,"qs":[{"q":"drug effects","mj":false,"ui":"Q000187"}],"ui":"D006706"},{"d":"Humans","mj":false,"ui":"D006801"},{"d":"Hypoglycemic Agents","mj":false,"qs":[{"q":"pharmacology","mj":false,"ui":"Q000494"}],"ui":"D007004"},{"d":"Insulin Resistance","mj":false,"qs":[{"q":"physiology","mj":false,"ui":"Q000502"}],"ui":"D007333"},{"d":"Ligands","mj":false,"ui":"D008024"},{"d":"Lipogenesis","mj":false,"qs":[{"q":"drug effects","mj":false,"ui":"Q000187"}],"ui":"D050155"},{"d":"Liver","mj":false,"qs":[{"q":"drug effects","mj":false,"ui":"Q000187"},{"q":"enzymology","mj":false,"ui":"Q000201"},{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D008099"},{"d":"Male","mj":false,"ui":"D008297"},{"d":"Mice","mj":false,"ui":"D051379"},{"d":"Mice, Inbred C57BL","mj":false,"ui":"D008810"},{"d":"Mice, Knockout","mj":false,"ui":"D018345"},{"d":"Phosphatidylcholines","mj":false,"qs":[{"q":"metabolism","mj":true,"ui":"Q000378"},{"q":"pharmacology","mj":false,"ui":"Q000494"}],"ui":"D010713"},{"d":"Protein Binding","mj":false,"ui":"D011485"},{"d":"Receptors, Cytoplasmic and Nuclear","mj":false,"qs":[{"q":"agonists","mj":false,"ui":"Q000819"},{"q":"deficiency","mj":false,"ui":"Q000172"},{"q":"genetics","mj":false,"ui":"Q000235"},{"q":"metabolism","mj":true,"ui":"Q000378"}],"ui":"D018160"},{"d":"Signal Transduction","mj":false,"qs":[{"q":"drug effects","mj":false,"ui":"Q000187"}],"ui":"D015398"},{"d":"Triglycerides","mj":false,"qs":[{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D014280"}],"chemicals":[{"n":"Bile Acids and Salts","ui":"D001647","reg":"0"},{"n":"Blood Glucose","ui":"D001786","reg":"0"},{"n":"Hypoglycemic Agents","ui":"D007004","reg":"0"},{"n":"Ligands","ui":"D008024","reg":"0"},{"n":"Nr5a2 protein, mouse","ui":"C431936","reg":"0"},{"n":"Phosphatidylcholines","ui":"D010713","reg":"0"},{"n":"Receptors, Cytoplasmic and Nuclear","ui":"D018160","reg":"0"},{"n":"Triglycerides","ui":"D014280","reg":"0"},{"n":"1,2-dilauroylphosphatidylcholine","ui":"C015153","reg":"18285-71-7"}],"comments_corrections":null,"source_flags":5,"s2_open_access_pdf_url":null,"s2_open_access_landing_url":null,"s2_open_access_license":null,"s2_open_access_status":null,"pmc_open_access_pdf_url":null,"pmc_open_access_landing_url":null,"pmc_open_access_license":null,"pmc_open_access_status":null,"unpaywall_open_access_pdf_url":null,"unpaywall_open_access_landing_url":null,"unpaywall_open_access_license":null,"unpaywall_open_access_status":null,"abstract":"Nuclear hormone receptors regulate diverse metabolic pathways and the orphan nuclear receptor LRH-1 (also known as NR5A2) regulates bile acid biosynthesis. Structural studies have identified phospholipids as potential LRH-1 ligands, but their functional relevance is unclear. Here we show that an unusual phosphatidylcholine species with two saturated 12 carbon fatty acid acyl side chains (dilauroyl phosphatidylcholine (DLPC)) is an LRH-1 agonist ligand in vitro. DLPC treatment induces bile acid biosynthetic enzymes in mouse liver, increases bile acid levels, and lowers hepatic triglycerides and serum glucose. DLPC treatment also decreases hepatic steatosis and improves glucose homeostasis in two mouse models of insulin resistance. Both the antidiabetic and lipotropic effects are lost in liver-specific Lrh-1 knockouts. These findings identify an LRH-1 dependent phosphatidylcholine signalling pathway that regulates bile acid metabolism and glucose homeostasis.","claims":[{"public_id":"cl_8a7495617a4fd5b3d3099c54f7c33c4a","status":"active","text":"An LRH-1-dependent phosphatidylcholine signaling pathway regulates bile acid metabolism and glucose homeostasis.","confidence":0.94,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_8a7495617a4fd5b3d3099c54f7c33c4a"},{"public_id":"cl_1628dbd93e0c5e106b687fbf3d7155e8","status":"active","text":"DLPC treatment decreases hepatic steatosis and improves glucose homeostasis in two mouse models of insulin resistance.","confidence":0.97,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_1628dbd93e0c5e106b687fbf3d7155e8"},{"public_id":"cl_aa16fec5c3289e0a1c2ac5debf3f5c9d","status":"active","text":"DLPC treatment induces bile acid biosynthetic enzymes in mouse liver, increases bile acid levels, and lowers hepatic triglycerides and serum glucose.","confidence":0.98,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_aa16fec5c3289e0a1c2ac5debf3f5c9d"},{"public_id":"cl_46ed6135172e1c31c9c79529ef32f503","status":"active","text":"Dilauroyl phosphatidylcholine is an LRH-1 agonist ligand in vitro.","confidence":0.98,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_46ed6135172e1c31c9c79529ef32f503"},{"public_id":"cl_565d779f64a32dc1aee9818dfccfb33a","status":"active","text":"The antidiabetic and lipotropic effects of DLPC are lost in liver-specific Lrh-1 knockouts.","confidence":0.96,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_565d779f64a32dc1aee9818dfccfb33a"}],"concepts":[{"public_id":"co_26b0303121af8b27de7b7b6fc54c00fc","status":"active","name":"mouse liver","description":"The liver tissue of mice used here as the site of DLPC-responsive metabolic effects.","types":["biological tissue"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_26b0303121af8b27de7b7b6fc54c00fc"},{"public_id":"co_51d8763093ee0f7cb1e41ffa44627025","status":"active","name":"LRH-1","description":"An orphan nuclear hormone receptor involved in regulation of metabolic pathways.","types":["nuclear receptor"],"aliases":["NR5A2","liver receptor homolog-1"],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_51d8763093ee0f7cb1e41ffa44627025"},{"public_id":"co_5df9f069f793d017eb2eff052a94d7c8","status":"active","name":"dilauroyl phosphatidylcholine","description":"A phosphatidylcholine species with two saturated 12-carbon fatty acid acyl side chains.","types":["ligand","phospholipid"],"aliases":["DLPC"],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_5df9f069f793d017eb2eff052a94d7c8"},{"public_id":"co_644dc4fc2ee859c82012f88b0fae4dcd","status":"active","name":"hepatic steatosis","description":"Accumulation of fat in the liver.","types":["condition"],"aliases":["fatty liver"],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_644dc4fc2ee859c82012f88b0fae4dcd"},{"public_id":"co_6795d3854370bc0164ffac58188c779e","status":"active","name":"agonist ligand","description":"A molecule that binds to a receptor and activates its signaling activity.","types":["molecular interaction"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_6795d3854370bc0164ffac58188c779e"},{"public_id":"co_69237856bcc125b354e77402d8ec7051","status":"active","name":"bile acid metabolism","description":"The synthesis, regulation, and handling of bile acids.","types":["metabolic process"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_69237856bcc125b354e77402d8ec7051"},{"public_id":"co_77e8315c122191af422dcbab9913d4b3","status":"active","name":"antidiabetic and lipotropic effects","description":"Effects that reduce diabetic symptoms and promote lipid mobilization or reduced liver fat.","types":["effect"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_77e8315c122191af422dcbab9913d4b3"},{"public_id":"co_96016c9960109f60cf088335c9486a4e","status":"active","name":"glucose homeostasis","description":"The physiological regulation of blood glucose levels.","types":["metabolic process"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_96016c9960109f60cf088335c9486a4e"},{"public_id":"co_b8ff98987652e727ce635db3bc09f488","status":"active","name":"liver-specific Lrh-1 knockouts","description":"Mouse models in which Lrh-1 is deleted specifically in the liver.","types":["animal model"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_b8ff98987652e727ce635db3bc09f488"},{"public_id":"co_e91eb656c84b67fbe287384810835431","status":"active","name":"LRH-1-dependent phosphatidylcholine signalling pathway","description":"A phosphatidylcholine-mediated signaling pathway that requires LRH-1 activity.","types":["signaling pathway"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_e91eb656c84b67fbe287384810835431"},{"public_id":"co_ee236ebb55a70fac55a05751aec8ebea","status":"active","name":"bile acid biosynthetic enzymes","description":"Enzymes involved in the synthesis of bile acids.","types":["enzyme"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_ee236ebb55a70fac55a05751aec8ebea"}],"external_ids":{"DOI":"10.1038/nature10111","ArXiv":null,"PubMed":21614002,"PubMedCentral":"3150801","MAG":2033997896,"DBLP":null,"ACL":null},"open_access":{"is_open_access":false,"pdf_url":null,"landing_url":"https://sah.borca.ai/papers/195688640","source":null,"pdf_url_source":null,"license":null,"reason":"pdf_url_not_indexed"},"reference_availability":{"status":"available","references_indexed":true,"full_text_available":false,"full_text_source":null,"count_basis":"semantic_scholar_metadata","extraction_status":"not_applicable","reason":null},"source":{"provider":"episteme2","base_corpus":"semantic_scholar_dump","freshness_mode":"unknown","basis":["semantic_scholar_metadata","postgres_metadata"],"limits":["paper metadata is based on indexed upstream scholarly datasets","claims and concepts are available only for extracted papers","absence of claims or concepts means no extracted graph data is available in this response"],"status":"available","degraded":false,"degraded_reasons":[],"diagnostics":{"status":"available","degraded":false,"degraded_reasons":[],"metadata_status":"available","graph_status":"available","abstract_status":"available"},"source_flags":5},"paper_id":634503,"paper_uid":"f4ca3cc7-03db-47c5-a962-dad167461ad9","canonical_identity":{"paper_id":634503,"paper_uid":"f4ca3cc7-03db-47c5-a962-dad167461ad9","identity_status":"available","lookup_basis":"semantic_scholar_external_id","compatibility_path":"corpus_id"},"url":"https://sah.borca.ai/papers/195688640"}