{"doi":"10.1172/jci131190","title":"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.","journal":"Journal of Clinical Investigation","year":2020,"id":52948,"datarank":0.7242470605953454,"base_score":4.8283137373023015,"endowment":4.8283137373023015,"self_citation_contribution":0.7242470605953454,"citation_network_contribution":0.0,"self_endowment_contribution":0.7242470605953454,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":124,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9586,"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":268741,"name":"Wondong Kim","orcid":"0000-0001-9030-9164","position":1,"is_corresponding":false},{"id":268742,"name":"Wen Zhou","orcid":"0000-0001-8455-6011","position":2,"is_corresponding":false},{"id":6943,"name":"Kerry A. 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