Phosphorus restriction does not prevent the increase in fibroblast growth factor 23 elicited by high fat diet

This study was designed to evaluate the influence of phosphorus (P) restriction on the deleterious effects of high fat diets on mineral metabolism. Twenty-four rats were allotted to 3 groups (n = 8 each) that were fed different diets for 7 months. Rats in group 1 were fed normal fat-normal P (0.6%) diet (NF-NP), rats in group 2 were fed high fat-normal P diet (HF-NP) and rats in group 3 were fed high fat-low P (0.2%) diet (HF-LP). Blood, urine and tissues were collected at the end of the experiments. When compared with the control group (NF-NP), rats fed HF diets showed increases in body weight, and in plasma concentrations of triglycerides and leptin, and decreased plasma calcitriol concentrations. In rats fed HF-NP plasma fibroblast growth factor 23 (FGF23) was higher (279.6 +/- 39.4 pg/ml vs 160.6 +/- 25.0 pg/ml, p = 0.018) and renal klotho (ratio klotho/GAPDH) was lower (0.75 +/- 0.06 vs 1.06 +/- 0.08, p<0.01) than in rats fed NF-NP. Phosphorus restriction did not normalize plasma FGF23 or renal klotho; in fact, rats fed HF-LP, that only ingested an average of 22.9 mg/day of P, had higher FGF23 (214.7 +/- 32.4 pg/ml) concentrations than rats fed NF-NP (160.6 +/- 25.0 pg/ml), that ingested and average of 74.4 mg/day of P over a 7 month period. In conclusion, our results demonstrate that severe P restriction over a prolonged period of time (7 months) does not normalize the increase in circulating FGF23 induced by HF diets. These data indicate that the deleterious effects of high fat diet on the FGF23/klotho axis are not eliminated by reduced P intake.