Purpose: Omega 3 fatty acid showed the protective effect against various renal injuries. Recently, it is reported that Omega 3 regulates the autophagy. Using fat-1 transgenic mice, a well-established animal model that endogenously synthesizes Omega 3 fatty acid, we evaluated whether [omega]3-PUFA may attenuate ischemiareperfusion (IR) injury, and evaluated associating mechanism.

Methods: C57Bl/6 background fat-1 mice and wild type mice were divided into 4 groups; wild type sham, fat-1 sham, wild type IR (reperfusion 35 minutes after clamping of both renal artery and vein) renal injury, and fat-1 IR renal injury. Kidneys and blood were harvested 24hr after IR injury. Real time RT-PCR, western blot and immunohistochemistry for molecular study and H&E stain and PAS stain for histologic examination were performed.

Results: fat-1 IR mice kidney showed improvement of renal cell survival, renal function, and pathologic damage compared to wild-type (WT) mice kidney. Also, fat-1 IR mice kidney showed the decreased oxidative stress and apoptosis. Compared to WT IR mice kidney. WT IR mice kidney higher amounts of LC3, Beclin-1, Atg7 and p62, compared to sham mice kidney. Fat-1 IR mice kidney showed higher amounts of LC3, Beclin-1 and Atg7 and lower amounts of p62 compared to WT IR mice kidney. In addition, renal cathepsin D and ATP6E were also increased in fat-1 IR mice kidney compared to WT IR mice kidney. Further, there was also increased AMPK activation in fat-1 IR mice kidney. AMPK activation led to inhibition of phosphorylation of the mechanistic target of rapamycin (MTOR) in fat-1 IR mice kidney.

Conclusion:Omega 3 fatty acid in fat-1 mice as contributing to AMPK-mediated autophagy activation leading to a reno-protective response, as a novel kidney defense mechanism.

CITATION INFORMATION: Kim J.-J, Jeong J, Choi D, Na K, Lee K. Omega 3 Attenuates Ischemia Reperfusion Renal Injury via Enhancement of Autophagy Flux. Am J Transplant. 2017;17 (suppl 3).

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