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Glycerol-3-phosphate is an FGF23 regulator derived from the injured kidney
- Source :
- J Clin Invest, The Journal of clinical investigation, vol 130, iss 3
- Publication Year :
- 2020
- Publisher :
- American Society for Clinical Investigation, 2020.
-
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 D(3) [1,25(OH)(2)D] 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.
- Subjects :
- 0301 basic medicine
Nephrology
Fibroblast growth factor 23
Male
Glycerol
Kidney Disease
urologic and male genital diseases
Kidney
Medical and Health Sciences
chemistry.chemical_compound
Mice
0302 clinical medicine
Bone disease
Chronic kidney disease
Receptors
Lysophosphatidic acid
Homeostasis
2.1 Biological and endogenous factors
Aetiology
Receptors, Lysophosphatidic Acid
Mice, Knockout
Chemistry
Acute kidney injury
General Medicine
Acute Kidney Injury
medicine.anatomical_structure
030220 oncology & carcinogenesis
Glycerophosphates
Bone Biology
Female
Research Article
medicine.medical_specialty
Knockout
Immunology
Renal and urogenital
Lysophosphatidic Acid
Cell Line
Phosphates
03 medical and health sciences
Internal medicine
medicine
Metabolomics
Animals
Humans
LPAR1
medicine.disease
Fibroblast Growth Factors
stomatognathic diseases
Fibroblast Growth Factor-23
030104 developmental biology
Endocrinology
Renal phosphate excretion
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- J Clin Invest, The Journal of clinical investigation, vol 130, iss 3
- Accession number :
- edsair.doi.dedup.....c2f75e0080f75bc5a096dead97c4a4da