Abstract: FR-PO1066
Sex-Specific Metabolic Dysfunction and Reduced Lifespan Induced by Long-Term, Low-Dosage Dietary Phosphorus Loading in Mice
Session Information
- Health Maintenance, Nutrition, and Metabolism
November 07, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Health Maintenance, Nutrition, and Metabolism
- 1500 Health Maintenance, Nutrition, and Metabolism
Authors
- Matsumoto, Ayumi, Osaka Daigaku, Suita, Osaka Prefecture, Japan
- Matsui, Isao, Osaka Daigaku, Suita, Osaka Prefecture, Japan
- Imai, Atsuhiro, Osaka Daigaku, Suita, Osaka Prefecture, Japan
- Okushima, Hiroki, Osaka Daigaku, Suita, Osaka Prefecture, Japan
- Inoue, Kazunori, Osaka Daigaku, Suita, Osaka Prefecture, Japan
- Isaka, Yoshitaka, Osaka Daigaku, Suita, Osaka Prefecture, Japan
Background
Modern diets contain high phosphorus burden, resulting in chronic phosphorus loading throughout the lifespan. Previous studies have demonstrated that acute, high-dose (2-3%) phosphorus loading leads to hyperphosphatemia and subsequent organ damage, including kidney and vessels. However, the effects of long-term, low-dose phosphorus loading without hyperphosphatemia, a common human condition, remain unclear. This study examined the effects of long-term, low-dose dietary phosphorus on organisms.
Methods
We conducted a long-term animal study using male and female mice randomly assigned to two dietary groups: Control group (0.84% phosphorus) and Pi group (1% phosphorus). The study involved glucose tolerance, insulin sensitivity assessment and histological examination of kidney, liver and pancreas at 6months. Survival rates were assessed at 24 months, alongside regular evaluation of serum phosphorus levels, renal function, and body weight.
Results
Both dietary groups maintained comparable food intake, serum phosphorus levels, and renal function, regardless of sex. Both male and female mice in the Pi group exhibited increased urinary phosphorus excretion and weight gain. However, only male mice in the Pi group showed significantly reduced survival rates, glucose intolerance and hepatic lipid accumulation. In contrast, female mice showed no difference in survival rates between dietary groups. Real-time PCR analysis of liver revealed increased mRNA levels of beta-oxidation related genes in the Pi group among female mice, while no differences between groups were observed in male mice.
Conclusion
Long-term, low-dose phosphorus loading induces metabolic alterations and reduced lifespan in a sex-specific manner, even without hyperphosphatemia. The male-specific effects on metabolism and survival suggest important sex differences in phosphorus handling and its metabolic consequences. These results may explain the sex-specific outcomes observed in CKD patients, susceptible to phosphorus dysregulation. Our findings offers a platform for investigating the long-term phosphorus excess on metabolic health and aging, with potential implications for understanding sex differences in disease progression and treatment outcomes.