ArticleThe Journal of clinical investigation2023
Kidney glycolysis serves as a mammalian phosphate sensor that maintains phosphate homeostasis.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 65 citations in OpenAlex.
- FGF23 - A hormone produced by bone and has many faces.Reviews in endocrine & metabolic disorders · 2026Review
- Review
- Phosphate homeostasis and endocrine regulators.Pediatric nephrology (Berlin, Germany) · 2026Article
- Intra-mitochondrial glycolysis maintains mitochondrial function and underlies the pathogenesis of retinitis pigmentosa.Nature communications · 2026Article
- Glycerol enhances mitochondrial metabolism and inflammatory response in pro-inflammatory macrophages.EMBO reports · 2026Article
- Markers of Mineral Metabolism in Children With CKD Stages 2 to 5D.Kidney international reports · 2026Article
- The effects of elevated phosphate on the kidney - damaging the gatekeeper.Pflugers Archiv : European journal of physiology · 2026Review
- Development of a severe rat refeeding syndrome model and mathematical modeling of the associated hypophosphatemia.NPJ systems biology and applications · 2026Article
- Association between Serum Glycerol-3-Phosphate and Fibroblast Growth Factor-23 in Nondiabetic Patients on Hemodialysis.Clinical journal of the American Society of Nephrology : CJASN · 2026Article
- A genetically encoded bifunctional enzyme mitigates redox imbalance and lipotoxicity.Nature metabolism · 2026Article
- Lysophosphatidic Acid Synergizes With 1,25-Dihydroxyvitamin D to Promote Fibroblast Growth Factor-23 Synthesis via MAPK Signaling and Induction of the IL12A Gene.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Gut microbiota in chronic kidney disease-mineral and bone disorder: shared mechanisms, disease-specific signatures, and therapeutic prospects.Frontiers in endocrinology · 2026Review
- Chronic kidney disease as an active driver of digestive tract tumors: mechanistic insights and emerging management strategies.Frontiers in cell and developmental biology · 2026Review
- TGFβ signaling regulates the response of the skeleton to phosphate.bioRxiv : the preprint server for biology · 2025Article
- The role of bone in whole-body energy metabolism.Nature reviews. Endocrinology · 2025Review
- Network Interactions of Circulating FGF23, HRG-HMGB1, and Cardiac Disease in CKD.Journal of the American Society of Nephrology : JASN · 2025Article
- Updates on renal phosphate transport.Current opinion in nephrology and hypertension · 2025Review
- Hyperphosphatemia in Kidney Failure: Pathophysiology, Challenges, and Critical Role of Phosphorus Management.Nutrients · 2025Review
- Fibroblast growth factor 23 and fibroblast growth factor receptor 4 promote cardiac metabolic remodeling in chronic kidney disease.Kidney international · 2025Article
- Integrated single-cell transcriptomic map of pig kidney cells across various periods and anatomical sites.Zoological research · 2025Article
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15 authors at 2 institutions in 1 country.
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Abstract
How phosphate levels are detected in mammals is unknown. The bone-derived hormone fibroblast growth factor 23 (FGF23) lowers blood phosphate levels by reducing kidney phosphate reabsorption and 1,25(OH)2D production, but phosphate does not directly stimulate bone FGF23 expression. Using PET scanning and LC-MS, we found that phosphate increases kidney-specific glycolysis and synthesis of glycerol-3-phosphate (G-3-P), which then circulates to bone to trigger FGF23 production. Further, we found that G-3-P dehydrogenase 1 (Gpd1), a cytosolic enzyme that synthesizes G-3-P and oxidizes NADH to NAD+, is required for phosphate-stimulated G-3-P and FGF23 production and prevention of hyperphosphatemia. In proximal tubule cells, we found that phosphate availability is substrate-limiting for glycolysis and G-3-P production and that increased glycolysis and Gpd1 activity are coupled through cytosolic NAD+ recycling. Finally, we show that the type II sodium-dependent phosphate cotransporter Npt2a, which is primarily expressed in the proximal tubule, conferred kidney specificity to phosphate-stimulated G-3-P production. Importantly, exogenous G-3-P stimulated FGF23 production when Npt2a or Gpd1 were absent, confirming that it was the key circulating factor downstream of glycolytic phosphate sensing in the kidney. Together, these findings place glycolysis at the nexus of mineral and energy metabolism and identify a kidney-bone feedback loop that controls phosphate homeostasis.
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