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Abstract: SA-PO255

Mechanistic Role of Renal Tubular Mitochondrial AKT1 in Metabolic Syndrome-Induced Renal Injuries

Session Information

Category: Diabetic Kidney Disease

  • 601 Diabetic Kidney Disease: Basic


  • Lin, Hugo Y.-H., kaohsiung municipal Ta-Tung Hospital, Kaohsiung, Taiwan
  • Yen, Chia-Hung, Kaohsiung Medical University, Kaohsiung, Taiwan
  • Chen, Yi-Siao, Kaohsiung Medical University, Kaohsiung, Taiwan
  • Chen, I-Ya, Chang Gung University, Taoyuan, Taoyuan, Taiwan
  • Huang, Jee-Fu, Kaohsiung Medical University, Kaohsiung, Taiwan
  • Lu, Tzongshi, Brigham and Women's Hospital Department of Medicine, Boston, Massachusetts, United States

Metabolic syndrome (MetS) is associated with kidney diseases, but the etiology is inconclusive. Recent evidence suggests that mitochondrial dysfunction, which can be modulated by AKT1, may play a critical role in kidney injury. We hypothesized that renal tubular mitochondrial AKT1 signaling plays a mechanistic role in the pathogenesis of kidney injuries in MetS.


We executed the study with 8-week C57BL/6 male mice fed with high fat diet (21.1% fat, 41% sucrose, and 1.25% cholesterol by weight) and a high sugar solution (23.1g/L d-fructose, and 18.9g/L d-glucose) for six months, compared with mice fed with normal chow diet and normal tap water.


In our murine MetS model, the body weight was raised (p<0.001). The kidney size as a percentage of body weight was similar (p=0.765). For the glucose tolerance test, the fasting glucose level was significantly higher in MetS mice as compared to normal diet mice (p=0.003). From 15 to 120 minutes, the glucose levels were significantly elevated (p=0.022). The shape of the intraperitoneal glucose tolerance test curve at three months was dissimilar to that at six months, and the AUC value at six months was higher (p=0.013). The fasting hyperinsulinlemia (p=0.017) and insulin resistance measured by Homeostatic Model Assessment for Insulin Resistance was elevated (p=0.003). For renal function, although serum BUN (p= 0.785) and creatinine (p=0.654) in MetS mice were not changed, the proteinuria (p=0.023), and the urine KIM-1 (p=0.014) were raised. There were prominent glomerulosclerosis index (p=0.032), tubulointerstitial fibrosis score (p=0.015), tubular dilatation score (p=0.038), tubular vacuolation score (p=0.028), and tubular casts (p=0.031) of renal histology. To further dissect the role of mitochondrial AKT1 signaling during MetS in the renal tubules, we have examined the mitochondrial AKT1 protein. There was increasing accumulation of phyosphorylated AKT1 (p=0.030) in the mitochondria at proximal tuble after MetS. AKT1 translocation was confirmed with immunohistochemistry stain and western blots of mitochondria proteins.


These findings shed new light on the mechanistic role of renal tubular mitochondrial AKT1 in MetS-induced kidney injuries and may be used to develop new strategies for the prevention and treatment of kidney diseases.


  • Government Support – Non-U.S.