Hypocaloric Diet Prevents the Decrease in FGF21 Elicited by High Phosphorus Intake

Abstract

The effect of dietary phosphorus (P) on fibroblast growth factor 21 (FGF21)/β-klotho axis was investigated in rats that were fed diets with: Normal (NP) or high P (HP) and either normal (NC), high (HC) or low calories (LC). Sampling was performed at 1, 4 and 7 months. Plasma FGF21 concentrations were higher (p < 0.05) in NC and HC than in LC groups. Increasing P intake had differing effects on plasma FGF21 in rats fed NC and HC vs. rats fed LC at the three sampling times. When compared with the NP groups, FGF21 concentrations decreased at the three sampling points in rats fed NC-HP (80 vs. 194, 185 vs. 382, 145 vs. 403 pg/mL) and HC-HP (90 vs. 190, 173 vs. 353, 94 vs. 434 pg/mL). However, FGF21 did not decrease in rats fed LC-HP (34 vs. 20, 332 vs. 164 and 155 vs. 81 pg/mL). In addition, LC groups had a much lower liver FGF21 messenger ribonucleic acid/glyceraldehyde 3-phosphate dehydrogenase (mRNA/GAPDH) ratio (0.51 ± 0.08 and 0.56 ± 0.07) than the NC-NP (0.97 ± 0.14) and HC-NP (0.97 ± 0.22) groups. Increasing P intake reduced liver FGF21 mRNA/GAPDH in rats fed NC and HC to 0.42 ± 0.05 and 0.37 ± 0.04. Liver β-klotho mRNA/GAPDH ratio was lower (p < 0.05) in LC groups (0.66 ± 0.06 and 0.59 ± 0.10) than in NC (1.09 ± 0.17 and 1.03 ± 0.14) and HC (1.19 ± 0.12 and 1.34 ± 0.19) groups. A reduction (p < 0.05) in β-klotho protein/α-tubulin ratio was also observed in LC groups (0.65 ± 0.05 and 0.49 ± 0.08) when compared with NC (1.12 ± 0.11 and 0.91 ± 0.11) and HC (0.93 ± 0.17 and 0.87 ± 0.09) groups. In conclusion β-klotho is potently regulated by caloric restriction but not by increasing P intake while FGF21 is regulated by both caloric restriction and increased P intake. Moreover, increased P intake has a differential effect on FGF21 in calorie repleted and calorie depleted rats.

Fibroblast growth factor 21 (FGF21) is a sensitive marker of osteoporosis in haemodialysis patients: a cross-sectional observational study

“…In addition to HD cohort, the relationship between FGF21 and bone mineral density was observed in normal kidney function as well [38]. The relevant mechanism could be explained by the following facts: (1) physiological or pharmacological elevation of FGF21 induced IGFBP1 expression, which could be secreted into circulation and stimulate osteoclast differentiation, bone resorption and reduce bone mass [18]; (2) a previous study showed that IGFBP1 was significantly increased in patients on HD compared to healthy controls [35], which is consistent with our result that IGFBP1 levels are nearly eight times higher in the osteoporosis group than in the nonosteoporosis group (data not shown); and (3) FGF21 functions to trigger intracellular calcium release [39] and increase phosphate intake [40], which is in line with our result that FGF21 had a positive relationship with serum calcium levels in this study (Table 5). Different from the role of FGF23 in regulating calcium and phosphorus levels, FGF21 is mainly involved in bone metabolism by influencing bone cells formation.…”