Abstract: FR-PO1047
1,3-Butanediol Decreases Unilateral Ureteral Obstruction (UUO)-Induced Tubulointerstitial Inflammation and Fibrosis by Regulating the mTORC1 Signaling Pathway
Session Information
- CKD Mechanisms: Progression, Fibrosis, and Beyond
November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2303 CKD (Non-Dialysis): Mechanisms
Authors
- Li, Wenjia, Jeonbuk National University Medical School, Jeonju, Jeollabuk-do , Korea (the Republic of)
- Wang, Tian, Jeonbuk National University Medical School, Jeonju, Jeollabuk-do , Korea (the Republic of)
- Lee, Soo jin, Jeonbuk National University Medical School, Jeonju, Jeollabuk-do , Korea (the Republic of)
- Shin, Yujin, Jeonbuk National University Medical School, Jeonju, Jeollabuk-do , Korea (the Republic of)
- Kang, Kyung Pyo, Jeonbuk National University Medical School, Jeonju, Jeollabuk-do , Korea (the Republic of)
Background
Chronic kidney disease (CKD) has long been considered a prominent contributor to global mortality due to its extensive prevalence and profound negative consequences. Given the widespread prevalence and severe adverse impact of CKD, it is imperative to develop new strategies for the prevention and treatment. Acetoacetate, β-hydroxybutyrate (BHB), and acetone can be called "endogenous ketone bodies." It has been suggested that renal ketogenesis, specifically BHB contributes to cell metabolism under conditions of energy deprivation, including fasting and exercise. This study evaluated the effect of exogenous BHB in UUO-injured renal inflammation and fibrosis mice.
Methods
Seven to eight-week-old male C57BL/6 mice were divided into four groups randomly and assessed whether unilateral ureteral obstruction operated or sham-operated in this experiment. The mice were administered with whether 20% 1,3-butanediol (1,3-BD) solution or vehicle served as a daily drink seven days before UUO surgery and continued for 14 days after surgery. We evaluated renal histology, immunohistochemistry, and immunofluorescent staining for renal tubulointerstitial inflammation and fibrosis. We also assessed proinflammatory cytokines and chemokines by qRT-PCR and western blotting.
Results
1,3-BD is an exogenous ketone body chemical that can be administered orally. 1,3-BD treatment mitigates UUO-induced renal tubular injury, inflammatory cell infiltration, and fibrosis. The inflammatory response was induced with the recruitment of inflammatory cells and tissue regeneration, and treatment of BHB in UUO-injured mice decreased proinflammatory cytokines and cell adhesion molecules expression. There was an increased phosphorylation/activation of mTORC1 signaling in the veh-treated UUO group, and it was attenuated after the administration of 1,3-BD.
Conclusion
Administration of 1,3-BD decreases the UUO-induced renal tubulointerstitial injury, inflammation, and fibrosis by suppressing the activation of the mTORC1 signaling pathway. Suppression of mTORC1 signaling might have a protective effect on UUO-induced tubular injury, fibrosis, and inflammation.
Funding
- Government Support – Non-U.S.