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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.
Elevated serum branched-chain amino acid (BCAA) concentrations are associated with obesity and insulin resistance and have been implicated in the onset and progression of diabetes; however, their relationship with diabetic kidney disease (DKD) remains unclear. This study investigated the impact of BCAA metabolic regulation on the development and progression of DKD.
SGLT2 inhibitor, Tofogliflozin (5mg/kg/day) was given to the db/m and db/db mice for 8 weeks. LC-MS for serum and kidney tissues was performed. To generate an experimental BCAA catabolism-enhanced model, the db/db and db/m mice were given 3,6-dichlorobenzo(b)thiophene-2-carboxylic acid (BT-2) (40mg/kg/day), a small molecule allosteric inhibitor of branched-chain α-keto acid dehydrogenase kinase (BDK) for 12 weeks. As an experimental model for BCAA overload, db/db and db/m mice were given a BCAA enrichment mixture (BCAAem) dissolved water for 8 weeks. The blood glucose levels, body weight, and food intake were regularly examined. Urinary albumin, serum leucine levels, and urinary thiobarbituric acid reactive substances (TBARS) were measured. PAS, PAM, and collagen IV staining were performed on FFPE sections. Mouse mesangial cel line, MES13 was incubated with BCAA, and the levels of collagen IV and proteins associated with mammalian target of rapamycin complex 1 (mTORC1) activation pathway were examined.
Metabolomic analysis revealed significantly increased renal and serum BCAA levels in db/db mice compared with db/m mice, and this elevation was suppressed by the SGLT2 inhibitor tofogliflozin. To further explore the effects of altered BCAA metabolism, two db/db mouse models were established: a BCAA catabolism–enhanced model using BT-2, and a BCAA-overload model using BCAAem. Molecular and histological analyses were subsequently performed. In the catabolism-enhanced model, serum leucine levels and glomerular Col IV accumulation were reduced, whereas in the overload model, serum leucine levels, albuminuria, and mesangial matrix expansion were increased. Because BCAAs are known activators of mTORC1, MES13 was stimulated with BCAAs to evaluate the expression of Col IV and mTORC1-related proteins. BCAA stimulation enhanced phosphorylation of S6 (pS6) and S6 kinase (pS6K) as well as Col IV expression, all of which were abrogated by mTOR inhibition.
These findings indicate that elevated BCAAs promote glomerular mesangial matrix expansion and albuminuria via activation of the mTORC1 signaling pathway, providing mechanistic insight into the link between altered amino acid metabolism and DKD progression.
