Energy-dense diets increase FGF23, lead to phosphorus retention and promote vascular calcifications in rats.

Abstract

Rats with normal renal function (Experiment 1, n=12) and uninephrectomized (1/2Nx) rats (Experiment 2, n=12) were fed diets with normal P (NP) and either normal (NF) or high fat (HF). Rats with intact renal function (Experiment 3, n=12) were also fed NF or HF diets with high P (HP). Additionally, uremic (5/6Nx) rats (n=16) were fed HP diets with NF or HF. Feeding the HF diets resulted in significant elevation of plasma FGF23 vs rats fed NF diets: Experiment 1, 593±126 vs 157±28pg/ml (p<0.01); Experiment 2, 538±105 vs 250±18pg/ml (p<0.05); Experiment 3, 971±118 vs 534±40pg/ml (p<0.01). Rats fed HF diets showed P retention and decreased renal klotho (ratio klotho/actin) vs rats fed NF diets: Experiment 1, 0.75±0.06 vs 0.97±0.02 (p<0.01); Experiment 2, 0.69±0.07 vs 1.12±0.08 (p<0.01); Experiment 3, 0.57±0.19 vs 1.16±0.15 (p<0.05). Uremic rats fed HF diet showed more severe vascular calcification (VC) than rats fed NF diet (aortic Ca=6.3±1.4 vs 1.4±0.1mg/g tissue, p<0.001). In conclusion, energy-rich diets increased plasma levels of FGF23, a known risk factor of cardiovascular morbidity and mortality. Even though FGF23 has major phosphaturic actions, feeding HF diets resulted in P retention, likely secondary to decreased renal klotho, and aggravated uremic VC