{"doi":"10.3410/f.737389609.793572183","title":"Faculty Opinions recommendation of Glycerol-3-phosphate is an FGF23 regulator derived from the injured kidney.","abstract":"Fibroblast growth factor 23 (FGF23) is a bone-derived hormone that controls blood phosphate levels by increasing renal phosphate excretion and reducing 1,25-dihydroxyvitamin D3 [1,25(OH)2D] production. Disorders of FGF23 homeostasis are associated with significant morbidity and mortality, but a fundamental understanding of what regulates FGF23 production is lacking. Because the kidney is the major end organ of FGF23 action, we hypothesized that it releases a factor that regulates FGF23 synthesis. Using aptamer-based proteomics and liquid chromatography-mass spectrometry-based (LC-MS-based) metabolomics, we profiled more than 1600 molecules in renal venous plasma obtained from human subjects. Renal vein glycerol-3-phosphate (G-3-P) had the strongest correlation with circulating FGF23. In mice, exogenous G-3-P stimulated bone and bone marrow FGF23 production through local G-3-P acyltransferase-mediated (GPAT-mediated) lysophosphatidic acid (LPA) synthesis. Further, the stimulatory effect of G-3-P and LPA on FGF23 required LPA receptor 1 (LPAR1). Acute kidney injury (AKI), which increases FGF23 levels, rapidly increased circulating G-3-P in humans and mice, and the effect of AKI on FGF23 was abrogated by GPAT inhibition or Lpar1 deletion. Together, our findings establish a role for kidney-derived G-3-P in mineral metabolism and outline potential targets to modulate FGF23 production during kidney injury. PMID: 32065590 Funding information This work was supported by: NIAMS NIH HHS, United States Grant ID: K08 AR067285 NHLBI NIH HHS, United States Grant ID: R01 HL133870 NIDDK NIH HHS, United States Grant ID: P01 DK011794 BLRD VA, United States Grant ID: IK6 BX004835 NHLBI NIH HHS, United States Grant ID: R01 HL132320 NIDDK NIH HHS, United States Grant ID: U01 DK106981 BLRD VA, United States Grant ID: I01 BX003453 NIAMS NIH HHS, United States Grant ID: R01 AR067291 NIDDK NIH HHS, United States Grant ID: R01 DK081572 NIDDK NIH HHS, United States Grant ID: R01 DK116716 NINR NIH HHS, United States Grant ID: R01 NR017399 NIDDK NIH HHS, United States Grant ID: K08 DK124568 More Less keyboard_arrow_down","journal":"Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature","year":2020,"id":133256,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9533,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":363544,"name":"Jason R. Stubbs","orcid":"0000-0003-4580-5745","position":0,"is_corresponding":true}],"reference_count":62,"raw_metadata":null,"created_at":"2026-07-18T23:16:17.577688Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}