Abstract: FR-PO0369
Fasting Enhances Ischemic Tolerance Due to Restoration of Adenosine Triphosphate (ATP) Levels via Elevation of β-Oxidation Activity
Session Information
- AKI: Mechanisms - Metabolism and Repair
October 23, 2026 | Location: Exhibit Hall A, 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, 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 maintain their intricate functions. We previously established an experimental method visualizing spatiotemporal ATP dynamics, which demonstrated that ATP recovery of proximal tubules (PTs) after ischemia reperfusion injury (IRI) in the acute phase was correlated with kidney prognosis. On the other hand, intermittent fasting has been reported to confer protective effects against ischemic damage in various organs. 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 control and 24h-fasted groups using ATP visualizing mice and two-photon microscopy, and assessed tubular damage in the chronic phase. RNA-seq analysis of the PT cells isolated from the kidneys[Microsof1] was also performed. Furthermore, β-oxidation activity in PTs during fasting was visualized using quinone methide (QM)-releasing probes.
Results
While no difference in ATP levels was observed in the PTs before ischemia, the ATP recovery in the PTs after IRI in the fasted group was greater than in the control group. Moreover, the fasted group showed reduced tubular damages 14 days after IRI. Notably, ATP recovery in the acute phase inversely correlated with tubular damage in the chronic phase. Gene ontology enrichment analysis of PT cells demonstrated upregulation of fatty acid metabolic pathways in fasted mice. Consistently, QM-releasing probes demonstrated increased β-oxidation in PTs during fasting in vivo. Etmoxir, a CPT1s inhibitor, partially attenuated ATP recovery after IRI in fasted mice, supporting the contribution of β-oxidation to the ATP recovery in the fasted mice.
Conclusion
These data indicate that fasting confers renoprotection, at least in part, through the improvement of ATP recovery after IRI following activation of β-oxidation in PTs.