Abstract: FR-PO0148
Elucidation of Kidney Ischemia Tolerance Mechanisms During Fasting Through Visualization of Energy Metabolism
Session Information
- AKI: Mechanisms - 2
November 07, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Okubo, Akihiro, Kyoto Daigaku Daigakuin Igaku Kenkyuka Igakubu, Kyoto, Kyoto Prefecture, Japan
- Yamamoto, Shinya, Kyoto Daigaku Daigakuin Igaku Kenkyuka Igakubu, Kyoto, Kyoto Prefecture, Japan
- Takahashi, Masahiro, Kyoto Daigaku Daigakuin Igaku Kenkyuka Igakubu, Kyoto, Kyoto Prefecture, Japan
- Yamamoto, Shigenori, Kyoto Daigaku Daigakuin Igaku Kenkyuka Igakubu, Kyoto, Kyoto Prefecture, Japan
- Yamamoto, Masamichi, Kokuritsu Junkankibyo Kenkyu Center, Suita, Osaka Prefecture, Japan
- Yanagita, Motoko, Kyoto Daigaku Daigakuin Igaku Kenkyuka Igakubu, Kyoto, Kyoto Prefecture, Japan
Background
The kidneys constantly require substantial amounts of ATP to meet the demands of their intricate functions. We previously established an experimental method that visualizes spatiotemporal ATP dynamics, which demonstrated that ATP recovery of proximal tubules (PTs) after ischemia reperfusion injury (IRI) was correlated with kidney prognosis. On the other hand, intermittent fasting has been reported to confer organ-protective effects against ischemic damage in the brains, hearts, and kidneys. Although previous studies have shown that this protective effect is partially due to a reduction in oxidative stress, the underlying metabolic mechanisms remain unclear. In this study, we examined ATP dynamics and β-oxidation activity before and after IRI in fasted mice.
Methods
We analyzed ATP dynamics during unilateral 30-minute IRI in the 1-day fasting and control groups, utilizing ATP visualizing mice and multiphoton microscopy, and assessed ATP recovery in the acute phase and tubular damage in the chronic phase. Next, we performed RNA-seq analysis of the PT cells isolated from the kidneys of fasted mice. Furthermore, we evaluated the β-oxidation activity in PTs during fasting using quinone methide (QM)-releasing probes, which visualizes the β-oxidation activity of fatty acids in vivo.
Results
There was no significant difference in ATP levels between the control and fasting groups in the PTs prior to ischemia. In contrast, the ATP recovery rates in the PTs 10 min after IRI in the fasting group were better than those in the control group. Moreover, the fasting group showed reduced tubular damage 14 days after IRI. Notably, ATP recovery rates in the acute phase were inversely correlated with tubular damage in the chronic phase. Gene ontology enrichment analysis showed upregulation of fatty acid metabolic pathways in the PT cells of fasting mice, which was also supported by the upregulation of β-oxidation in PTs visualized by administering QM-releasing probes in vivo during fasting.
Conclusion
These data indicate that the renoprotective effects during fasting could be partly due to the improvement in ATP recovery rate after IRI following activated β-oxidation in PTs.