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Abstract: TH-PO626

Nifedipine Modulates Renal Lipogenesis and Fibrosis via the AMPK/SREBP Transcriptional Pathway: An In Vivo CKD Model and Translational Study

Session Information

Category: Health Maintenance, Nutrition, and Metabolism

  • 1300 Health Maintenance, Nutrition, and Metabolism

Author

  • Lin, Yen Chung, Taipei Medical University Hospital, Taipei, Taiwan

Group or Team Name

  • Taipei Medical University
Background

Overproduced free fatty acid induces inflammation and renal fibrosis. Weight reduction therapy including calcium loading method may decrease the above renal damage. However, calcium channel blocker affects lipid accumulation in extra-adipose tissue is in debate. Therefore, we want to initiate study on CKD animal and patients to realize effect of nifedipine on lipogenesis and renal toxicity.

Methods

39 SD rat were divided in four groups including control, Doxorubicin (DR) treated, DR+nifedipine treated and high fat diet (HFD). In addition, nineteen renal transplant patients were also enrolled for the examination of graft fibrosis and lipid content via transient elastography. Lipogensis related enzymes including Sterol regulatory element-binding proteins (SREBPs), acetyl-coa carboxylase (ACC), fatty acid synthase (FAS), 5' AMP-activated protein kinase (AMPK) were tested.

Results

Hypertension and proteinuria were observed in DR, DR+Nifedipine and HFD group. However, TNF-α was expressed in DR group compared with control, and higher in DR+nefidipine group. (p<0.05) Renal fibrosis on pathology obviously occurred in DR and DR+nifedipine groups but not expressed in HFD group compared with control. (p<0.05) Immunohistochemistry of CD36 also significant higher in nifedipine treated group but not high fat diet group. (p<0.05) Western blot showed higher SREBP-1/2, ACC, and lower FAS. (p<0.05) P-AMPK/AMPK was lower in study groups. Low density cholesterol level was strongly correlated with graft kidney fibrosis and lipid accumulation. (p<0.05)

Conclusion

Nifedipine may potentiate renal fibrosis and lipid accumulation through SREBP-1/2 activation and lower AMPK activity in this in vivo study, similar results was observed in our previous in vitro study. Interestingly, hypercholesterolemia may correlate with renal fibrosis on graft kidney in CKD patients.