Abstract
BACKGROUND/OBJECTIVES: Bone-derived fibroblast growth factor 23 (FGF23) is a hormone that suppresses renal phosphate reabsorption and calcitriol (i.e., 1,25(OH)(2)D(3)) formation together with its co-receptor Klotho. FGF23- or Klotho-deficient mice suffer from rapid aging with multiple age-associated diseases, at least in part due to massive calcification. FGF23 is considered as a disease biomarker since elevated plasma levels are observed early in patients with acute and chronic disorders including renal, cardiovascular, inflammatory, and metabolic diseases. An energy-dense diet, which induces sequelae of the metabolic syndrome in humans and mice at least in part by enhancing pro-inflammatory TNFα formation, has recently been demonstrated to stimulate FGF23 production. METHODS: We investigated the relevance of TNFα for high-fat diet (HFD)-induced FGF23 formation in wild-type (tnf(+/+)) and TNFα-deficient (tnf(-/-)) mice. RESULTS: Within 3 weeks, HFD feeding resulted in a strong increase in the serum FGF23 level in tnf(+/+) mice. Moreover, it caused low-grade inflammation as evident from a surge in hepatic Tnfα transcript levels. TNFα stimulated Fgf23 transcription in UMR106 osteoblast-like cells. Serum FGF23 was significantly lower in tnf(-/-) mice compared to tnf(+/+) mice following HFD. Serum phosphate and calcitriol were not significantly affected by genotype or diet. CONCLUSIONS: We show that HFD feeding is a powerful stimulator of murine FGF23 production through TNFα formation.