Abstract: FR-PO0327
Mitochondrial AKT1 Activation in Renal Tubules Attenuates Kidney Injury and Immune Activation in Metabolic Syndrome
Session Information
- Diabetic Kidney Disease: Basic and Translational Science Advances - 1
November 07, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Diabetic Kidney Disease
- 701 Diabetic Kidney Disease: Basic
Authors
- Lin, Hugo Y.-H., Kaohsiung Medical University Chung Ho Memorial Hospital, Kaohsiung, Kaohsiung City, Taiwan
- Chen, Yen-Hua, National Sun Yat-sen University, Kaohsiung, Kaohsiung City, Taiwan
Background
Metabolic syndrome (MetS) is a significant risk factor for renal pathology; however, therapeutic strategies targeting its renal manifestations remain limited. Renal tubular cells are metabolically active and contain abundant mitochondria that respond to injury. We previously developed KMioxCAKT transgenic mice expressing mitochondria-targeted, constitutively active AKT1 (mito-AKT1) in renal proximal tubules upon tamoxifen induction with Cre-lox system. The aim of this study is to delineate the effects of tubular mito-AKT1 on metabolic regulation, kidney pathology, and immune modulation of MetS.
Methods
KMioxCAKT mice were treated with either corn oil or tamoxifen to regulate mito-AKT1 expression, then fed a high-fat diet for 16 weeks. Body weight was monitored, and kidney tissues were analyzed for histology and renal function. RT-PCR were assessed expression of inflammatory and regulatory T-cell genes.
Results
Tamoxifen-induced KMioxCAKT mice showed significantly lower body weight than controls at weeks 15 and 16 (p<0.05). Kidney function was preserved, with reduced serum creatinine (p=0.038) and proteinuria (p=0.041). Histological analysis revealed significant improvements in tubular injury (p=0.0235), vacuolization (p=0.032), nuclear dropout (p=0.031), glomerulosclerosis (p=0.043), and tubulointerstitial fibrosis (p<0.0001). RT-PCR showed decreased expression of pro-inflammatory genes (IL17, RORrt) and increased expression of regulatory marker Foxp3 (p=0.016), suggesting a shift toward a more immunoregulatory renal environment.
Conclusion
Renal mitochondrial AKT1 activation improves metabolic status, mitigates kidney injury, and alters renal immune gene expression in the setting of MetS. The KMioxCAKT mice offers a novel platform for studying renal immunometabolism and testing therapeutic strategies for kidney disease in metabolic disorders.
Funding
- Government Support – Non-U.S.