Glycerol-3-phosphate contributes to the increase in FGF23 production in chronic kidney disease

Why fibroblast growth factor 23 (FGF23) levels increase markedly in chronic kidney disease (CKD) is unknown. Recently, we found that phosphate stimulates renal production of glycerol-3-phosphate (G-3-P), which circulates to bone to trigger FGF23 production. To assess the impact of G-3-P on FGF23 production in CKD, we compared the effect of adenine-induced CKD in mice deficient in glycerol-3-phosphate dehydrogenase 1 (Gpd1), an enzyme that synthesizes G-3-P, along with wild-type littermates. We find that adenine diet causes a similar degree of renal insufficiency across genotype and that adenine-induced CKD increases blood G-3-P and FGF23 levels in wild-type mice. Further, we find that the increase in both G-3-P and FGF23 are significantly attenuated, but not fully abrogated, in