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Abstract: FR-PO595

Imbalance of Intestinal Microflora Disrupts LDL Receptor Pathway to Induce Lipid Accumulation at Renal Interstitium in Early Diabetic Nephropathy

Session Information

Category: Diabetes

  • 501 Diabetes Mellitus and Obesity: Basic - Experimental

Authors

  • Hu, Zebo, Zhongda Hospital, Southeast University Medical School, Nanjing City, JIANGSU , China
  • Ma, Kun ling, Zhongda Hospital, Southeast University Medical School, Nanjing City, JIANGSU , China
  • Zhang, Yang, Zhongda Hospital, Southeast University Medical School, Nanjing City, JIANGSU , China
  • Wang, Gui hua, Zhongda Hospital, Southeast University Medical School, Nanjing City, JIANGSU , China
  • Chen, Peipei, Zhongda Hospital, Southeast University Medical School, Nanjing City, JIANGSU , China
  • Lu, Jian, Zhongda Hospital, Southeast University Medical School, Nanjing City, JIANGSU , China
  • Lu, Chenchen, Zhongda Hospital, Southeast University Medical School, Nanjing City, JIANGSU , China
Background


Our previous studies demonstrated that lipid accumulation in kidneys contributes to the progression of diabetic nephropathy (DN). However, the exact mechanism of which caused lipid accumulation in kidney has not been completely elucidated. This study aimed to investigate the effect of imbalance of intestinal microflora on lipid deposition in the renal interstitium of DN.

Methods

Type 1 diabetic rats model were induced by streptozotocin injection. Broad-spectrum antibiotics were used to eliminate intestinal microflora. Intestinal microflora distribution was evaluated by 16S rDNA sequencing using samples from feces. Periodic acid-schiff (PAS) staining was used to observe basic structure and pathological changes of kidney. Lipid accumulation was detected by oil red O staining, Filipin staining, and intracellular free cholesterol quantitative assay. Immunohistochemical staining and Western blot were used to assess the protein expressions of low-density lipoprotein receptor (LDLr) pathway.

Results

Blautia, Roseburia, and Paraprevotella abundance were significantly increased in diabetic rats while Bacteroid abundance decreased when compared with the controls. Broad-spectrum antibiotics effectively cleared away intestinal microflora. PAS staining showed that tubular epithelium in diabetic mellitus group (DM group) exhibited obvious expansion, ballooning degeneration, cell detachment as well as increased glycogen deposition while antibiotics treatment alleviated those lesions. Lipid accumulation in tubular interstitium of diabetic rats was increased compared with the controls. After the application of antibiotics, the lipid accumulation in tubular interstitium of diabetic rats was significantly reduced. Moreover, immunohistochemical staining and Western blot suggested that LDLr expression in tubular interstitium was increased in DM group, while antibiotics treatment decreased LDLr expression.

Conclusion

Imbalance of intestinal microflora might disrupt LDLr pathway to induce lipid accumulation at renal interstitium in early diabetic nephropathy.