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Abstract: FR-PO188

Liraglutide Reduces Renal Tubular Ectopic Fat Deposition in Rats with Diabetic Nephropathy by Inhibiting Sterol Regulatory Element Binding Proteins

Session Information

Category: Diabetic Kidney Disease

  • 601 Diabetic Kidney Disease: Basic

Author

  • Su, Ke, Wuhan University, Wuhan, HUBEI, China
Background

Liraglutide, a long-acting GLP-1 receptor agonist, has show significantly improved renal outcomes in patients with T2DM and delayed the development of DN. But we still not know the renal protective mechanism of liraglutide.

Methods

30 SPF male Sprague-Dawley rats weighing 180-200 g were randomly divided into 3 group (n=10). Normal control group, DN group: diabetes+single nephrectomy group, Liraglutide treatment group: DN + liraglutide intervention group. Intraperitoneal injection of 35 mg/kg STZ and high fat diet to establish a T2DM model. The tail vein random blood glucose over 16.7 mmoL/L was determin to establish a T2DM model. T2DM group underwent unilateral nephrectomy at 1 week after modeling. After 1 week of nephrectomy, the subcutaneous injection of Liraglutide was given at a dose of 0.3 mg/kg/12 h for 12 weeks. Rat body weight was measured every 4 weeks during Liraglutide injection. Automated biochemical analyzer detected serum TG,TC,SCr,BUN,ALB, 24h urine protein at 12th week sacrificed. Sterol regulatory element binding protein (SREBP1) and fat differentiation-related protein (ADRP) were detected by immunohistochemical in 4% paraformaldehyde fixed rat renal.

Results

Liraglutide could decrease body weight of DN rat after 8th week (P<0.05). 24-hour urine protein quantitation showed a slight increase in the 10th week in DN group (867.03±17.2 0μg/24 hours), which was significantly higher in control group (289.98±37.85) (P<0.05), SCr, Urea and ALB were no significant change in 3 group. TG and TCh level were higher in DN than that in Liraglutide group (P<0.05) (Figure2). ADRP and SREBP1 tesed by immunohistochemistry expressed in renal tubules were significantly higher in DN than Liraglutide and control group (Figure1).

Conclusion

Liraglutide can reduce TG levels of DN rats via inhibiting SREBP1 in renal tubular and reduce fat ectopic deposition.

Funding

  • Government Support - Non-U.S.