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During the congress, E-Posters will be accessible to all participants on the congress website 24/7, as well as in the E-poster stations in the congress center.
Preparing your E-Poster
Please review the E-Poster format requirements carefully when preparing your E-Poster. Should your E-Poster not meet the mentioned requirements, it may not be displayed as described above.
E-Poster Submission Deadline
Please prepare and upload your E-Poster no later than March 14, 2026 11.59PM CET. After this date, you will no longer be able to prepare and upload your E-poster and it will not be displayed and accessible on the congress website.
Please follow the instructions below to input your abstract title.
Abstract titles should be brief and reflect the content of the abstract.
The global prevalence of diabetes continues to rise, with diabetic kidney disease (DKD) as its major microvascular complication, imposing substantial medical and socioeconomic burdens. Current therapies fail to halt DKD progression, highlighting the need for novel interventions. Short-chain fatty acids (SCFAs), key gut microbiota metabolites, have emerged as potential modulators of metabolic and renal diseases. This study investigated the protective effects of SCFAs on type 2 DKD and the underlying mechanisms.
Type 2 DKD was induced in db/db mice, which were then treated with SCFAs. Metabolomics, renal function tests, histopathology, and survival analysis were performed to evaluate therapeutic efficacy. Transcriptomic profiling, bioinformatics, and molecular assays were used to identify SCFAs-responsive pathways and targets. In vitro, high-glucose-induced podocyte injury models were used to evaluate the protective effects of SCFAs on podocyte injury and autophagy. Functional assays, including gene knockdown and overexpression, were conducted to explore the Nr1i3-Beclin 1 axis. Chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays were performed to confirm transcriptional regulation.
1) DKD mice exhibited decreased plasma SCFAs, which were restored by SCFAs supplementation, accompanied by improved survival, reduced blood glucose, serum creatinine, blood urea nitrogen, and albuminuria.
2) Histopathology revealed renal atrophy, glomerular basement membrane thickening, mesangial expansion, and collagen deposition in DKD mice, all alleviated by SCFAs.
3) Transmission electron microscopy indicated severe podocyte foot process effacement and reduced autophagosomes in DKD, whereas SCFAs improved foot process structure and autophagosome formation.
4) Transcriptomics showed downregulated SCFAs transport and autophagy pathways in DKD. Thirteen key SCFAs-responsive genes were identified, including nuclear receptor Nr1i3, predicted to regulate Beclin 1. Western blot confirmed that SCFAs partially restored Nr1i3 and autophagy-related protein expression.
5) Immunofluorescence showed reduced Nr1i3 and Beclin 1 co-localization in DKD glomeruli, which was enhanced by SCFAs. Similarly, SCFAs strengthened Nephrin and LC3B co-localization. In vitro, SCFAs dose-dependently promoted autophagy and alleviated podocyte injury, effects blocked by the autophagy inhibitor 3-MA.
6) Molecular docking revealed stable binding between SCFAs and Nr1i3, with overlapping sites for agonist TCPOBOP and inhibitor CINPA1. Immunofluorescence showed that Nr1i3 was mainly cytoplasmic under high glucose but translocated to the nucleus following SCFAs treatment, suggesting SCFAs-induced nuclear activation of Nr1i3.
7) Knockdown of Nr1i3 reduced Beclin 1, LC3B, and Nephrin expression and diminished SCFAs protection, while Nr1i3 overexpression enhanced these effects. Beclin 1 knockdown similarly impaired autophagy and podocyte markers without affecting Nr1i3, confirming Nr1i3 acts upstream.
8) ChIP-qPCR confirmed Nr1i3 binding to the Beclin 1 promoter, and dual-luciferase assays showed Nr1i3 overexpression activated Beclin 1 transcription.
SCFAs supplementation delays DKD progression by restoring podocyte autophagy and cytoskeletal integrity. Nr1i3 functions as a nuclear receptor for SCFAs, directly promoting Beclin 1 transcription and autophagy activation. The SCFAs–Nr1i3–Beclin 1 axis represents a potential therapeutic target for DKD.
