Abstract: FR-PO494
High Phosphate Diet Before Pregnancy Dysregulates Phosphate Metabolism in Neonatal Offspring Mice
Session Information
- Bone and Mineral Metabolism: Basic
October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Bone and Mineral Metabolism
- 401 Bone and Mineral Metabolism: Basic
Authors
- Hayashi, Mayu, Tokushima University, Tokushima, Japan
- Fukuda, Shiori, Tokushima University, Tokushima, Japan
- Kishimoto, Maki, Tokushima University, Tokushima, Japan
- Yamamoto, Hironori, Dept. of Health and Nutrition, Jin-ai University, Echizen city, Fukui, Japan
- Masuda, Masashi, Tokushima University, Tokushima, Japan
- Taketani, Yutaka, Tokushima University, Tokushima, Japan
Background
Excess intake of dietary phosphate (Pi) increases fibroblast growth factor 23 (FGF23) and parathyroid hormone (PTH) to maintain plasma Pi level. FGF23, is a potent phosphaturic factor, binds to α-klotho / FGFR complex in the kidney to promote excretion of Pi into urine. In addition, excess intake of dietary Pi also decreases in renal α-klotho expression. Downregulation or lack of α-klotho induces a premature aging-like phenotype such as ectopic calcification and osteoporosis resulted from hyperphosphatemia. Recent the theory of developmental origins of health and disease indicates that early exposure of dietary or environmental factors determines the risk of various diseases in adulthood. Thus, excess intake of dietary Pi during or before pregnant period may affect the gene expression of α-klotho or other Pi regulating factors related to future health risks in offsprings.
Methods
To investigate that, we used C57BL/6J female mice aged 8 weeks old. Mice were fed with either control Pi (CP) or high Pi (HP) diet for 21 days before pregnancy. At the end of diet control, they were mated with male mice and become pregnant. After the delivery, both groups were fed with CP diet. Neonatal offspring mice (at 3 weeks old when they were weaning) were subjected to analysis.
Results
As a result, although the no difference of Pi and calcium levels in breast milk between two groups, the offspring mice in HP diet group revealed plasma FGF23 concentration was significantly elevated, urinary Pi excretion tended to increase and urinary calcium excretion tended to decrease. Renal α-klotho mRNA expression level was not changed in the both groups. But interestingly, renal mRNA expression level of NaPi2c and CYP27B1, which are known to be suppressed by the FGF23/α-klotho signal was decreased in HP diet group. Femur mRNA expression level of Phex, which is known to FGF23 secretory suppression factor at the bone was increased in HP diet group. In addition, femur mRNA expression level of DNA methyltransferase (DNMT1) was significantly increased in HP diet group.
Conclusion
In conclusion, excessive dietary Pi intake before pregnant causes abnormal Pi metabolism, and it may be due to epigenetic modification through DNA methylation at bone.
Funding
- Government Support - Non-U.S.