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Abstract: TH-PO736

Ectopic Lipid Accumulation and Its Clinic Relevance in Type 2 Diabetic Kidney Disease Patients

Session Information

Category: Diabetes

  • 502 Diabetes Mellitus and Obesity: Clinical

Authors

  • Xiao, Li, The Second Xiangya Hospital, Central South University , Changsha, China
  • Luo, Ying, The Second Xiangya Hospital, Central South University , Changsha, China
  • Yang, Wenxia, The Second Xiangya Hospital, Central South University , Changsha, China
  • Liang, Hang, The Second Xiangya Hospital, Central South University , Changsha, China
  • Zhang, Fan, The Second Xiangya Hospital, Central South University , Changsha, China
  • Zhou, Yiming, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States
  • Zeng, Mengru, The Second Xiangya Hospital, Central South University , Changsha, China
  • Sun, Lin, The Second Xiangya Hospital, Central South University , Changsha, China
  • Liu, Fuyou, The Second Xiangya Hospital, Central South University , Changsha, China
Background

Growing evidence suggests that ectopic lipid accumulation may contribute to organ injury in the context of metabolic diseases, including diabetes. However, the ectopic lipid accumulation in the kidney and its clinic relevance in the patients with Diabetic kidney disease (DKD) remains unknown.

Methods

Twelve patients of type 2 DKD (stage II-III) were enrolled and kidney tissue biopsy were stained with Oil red and immunohistochemistry assay for key lipid droplet marker and regulator protein, including adipose differentiation-related protein (ADRP), sterol regulatory element binding protein-1 (SREBP-1) and PPAR-α, while 8 patients of MCD and 10 patients of primary FSGS served as the control. At the same time, the expression of serum and urine ADRP, β-NG and inflammation marker (IL-1, TNF-α) were also detected in 15 DM patients and 35 DKD patients (including 12 patients of stage III, 13 patients of stage IV and 10 patients of stage V) with ELISA. qPCR and western blot assay were used to detect the expression of SREBP-1 mRNA and protein from peripheral blood mononuclear cells (PBMC). The correlation of ADRP, SREBP-1 and the clinic parameter, inflammation and tubular damage were evaluated with Pearson (SPSS) analysis.

Results

We observed heavy lipid deposition and increased intracellular lipid droplets in the kidney, especially in proximal tubule of DKD patients, as compared to that of MCD and FSGS. In accordance with lipid accumulation, intensity of ADRP and SREBP expression in the kidney sections obviously increased, while PPAR-α expression decreased. Moreover, compared to DM patients, the expression of ADRP both in serum and urine were unregulated in DKD patients. Similarly, both mRNA and protein expression of SREBP1 from PBMC in DKD patients also increased. Notably, the urine ADRP level and the expression of SREBP showed a parallel change with that of serum creatinine, proteinuria, β-NG, IL-1and TNF-α expression and tubular-interstitial damage.

Conclusion

Aberrant lipid regulation and ecotopic kidney lipid accumulation were observed in the DKD patients, which correlated to the inflammation and disease progression. Suggesting that amelioration of ecotopic lipid deposit may provide a new approach for prevention of DKD.