Kidney Week

Abstract: SA-PO826

Amelioration of Renal Fibrosis and Tubulointerstitial Damage in Fat-1 Transgenic CKD Mice by Compensation of Decreased Omega-3 Fatty Acids in the Kidney

Session Information

• Molecular Mechanisms of CKD - III
  October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 1903 CKD (Non-Dialysis): Mechanisms

Authors

• Takahashi, Naohiro, Tokyo Medical and Dental University, Tokyo, Japan

Naohiro Takahashi,

• Kikuchi, Hiroaki, Tokyo Medical and Dental University, Tokyo, Japan

Hiroaki Kikuchi,

• Ishihara, Tomoaki, RIKEN-IMS, Yokohama, Japan

Tomoaki Ishihara,

• Arita, Makoto, RIKEN-IMS, Yokohama, Japan

Makoto Arita,

• Furusho, Taisuke, Tokyo Medical and Dental University, Tokyo, Japan

Taisuke Furusho,

• Ando, Fumiaki, Tokyo Medical and Dental University, Tokyo, Japan

Fumiaki Ando,

• Mori, Takayasu, Tokyo Medical and Dental University, Tokyo, Japan

Takayasu Mori,

• Isobe, Kiyoshi, Tokyo Medical and Dental University, Tokyo, Japan

Kiyoshi Isobe,

• Susa, Koichiro, Tokyo Medical and Dental University, Tokyo, Japan

Koichiro Susa,

• Nomura, Naohiro, Tokyo Medical and Dental University, Tokyo, Japan

Naohiro Nomura,

• Rai, Tatemitsu, Tokyo Medical and Dental University, Tokyo, Japan

Tatemitsu Rai,

• Uchida, Shinichi, Tokyo Medical and Dental University, Tokyo, Japan

Shinichi Uchida,

• Sohara, Eisei, Tokyo Medical and Dental University, Tokyo, Japan

Eisei Sohara,

Background

Although recent advances have led to better understanding of the linkage between inflammatory diseases and lipid mediators, little has been reported on the changes of lipid profile of kidney tissue in chronic kidney disease (CKD). Lipidomics is a powerful tool for the identification and the quantification of the lipid metabolites. In this study, we applied lipidomics to the kidney from the mice performed with subtotal nephrectomy, to identify specific lipid mediators as novel therapeutic targets in CKD.

Methods

Subtotal nephrectomy or oral administration of adenine was performed to C57BL/6J mice to establish CKD models. Kidney tissue samples from subtotal nephrectomy mice were analyzed with lipidomics to reveal lipid profile of CKD kidneys. We also analyzed the CKD models of fat-1 transgenic mice expressing the C. elegans fat-1 gene encoding an omega-3 fatty acid desaturase, leading to abundant omega-3 fatty acids in kidneys. To evaluate effects of lipid metabolites on fibrosis, we used cultured NRK-49F cells.

Results

Lipidomics analysis revealed that omega-3 fatty acids (EPA and DHA) and their downstream lipid metabolites were significantly decreased in CKD kidneys in comparison with sham control kidneys. Therefore, to investigate the effects of decreased omega-3 fatty acids on CKD kidneys, we examined two CKD models of fat-1 transgenic mice, subtotal nephrectomy and adenine-induced nephropathy. Alpha-SMA (a marker of renal fibrosis) and NGAL (a marker of tubulointerstitial damage) were suppressed in fat-1 transgenic CKD mice, suggesting that increased omega-3 fatty acids in kidney have beneficial effects on CKD. Some specific omega-3 fatty acid metabolites which were decreased in CKD kidneys attenuated fibroblast activation in vitro, indicating that they could be novel therapeutic lipid mediators for CKD treatment.

Conclusion

Lipidomics of the kidneys from subtotal-nephrectomy mice revealed reduction of omega-3 fatty acids and their down-stream lipid metabolites. Supplementation of omega-3 fatty acids and their downstream metabolites to kidneys might ameliorate tubulointerstitial damage and renal fibrosis in CKD.