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Article

High Endogenous Accumulation of ω-3 Polyunsaturated Fatty Acids Protect against Ischemia-Reperfusion Renal Injury through AMPK-Mediated Autophagy in Fat-1 Mice

1
Department of Anatomy, School of Medicine, Chungnam National University, Daejeon 35015, Korea
2
Department of Medical Science, School of Medicine, Chungnam National University, Daejeon 35015, Korea
3
Brain Research Institute, School of Medicine, Chungnam National University, Daejeon 35015, Korea
4
Department of Biomedical Science, Jungwon University, Geosan, Chungbuk 28023, Korea
5
Department of Nephrology, School of Medicine, Chungnam National University, Daejeon 35015, Korea
6
Department of Anatomy, College of Medicine, Konyang University, Daejeon 35365, Korea
7
Department of Biochemistry, School of Medicine, Chungnam National University, Daejeon 35015, Korea
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2017, 18(10), 2081; https://doi.org/10.3390/ijms18102081
Received: 3 August 2017 / Revised: 14 September 2017 / Accepted: 27 September 2017 / Published: 30 September 2017
(This article belongs to the Special Issue Omega-3 Fatty Acids in Health and Disease: New Knowledge)
Regulated autophagy is involved in the repair of renal ischemia-reperfusion injury (IRI). Fat-1 transgenic mice produce ω3-Polyunsaturated fatty acids (ω3-PUFAs) from ω6-Polyunsaturated fatty acids (ω6-PUFAs) without a dietary ω3-PUFAs supplement, leading to a high accumulation of omega-3 in various tissues. ω3-PUFAs show protective effects against various renal injuries and it has recently been reported that ω3-PUFAs regulate autophagy. We assessed whether ω3-PUFAs attenuated IR-induced acute kidney injury (AKI) and evaluated its associated mechanisms. C57Bl/6 background fat-1 mice and wild-type mice (wt) were divided into four groups: wt sham (n = 10), fat-1 sham (n = 10), wt IRI (reperfusion 35 min after clamping both the renal artery and vein; n = 15), and fat-1 IRI (n = 15). Kidneys and blood were harvested 24 h after IRI and renal histological and molecular data were collected. The kidneys of fat-1 mice showed better renal cell survival, renal function, and pathological damage than those of wt mice after IRI. In addition, fat-1 mice showed less oxidative stress and autophagy impairment; greater amounts of microtubule-associated protein 1A/1B-light chain 3 (LC3)-II, Beclin-1, and Atg7; lower amounts of p62; and, higher levels of renal cathepsin D and ATP6E than wt kidneys. They also showed more adenosine monophosphate-activated protein kinase (AMPK) activation, which resulted in the inhibition of phosphorylation of the mammalian target of rapamycin (mTOR). Collectively, ω3-PUFAs in fat-1 mice contributed to AMPK mediated autophagy activation, leading to a renoprotective response. View Full-Text
Keywords: ischemia-reperfusion injury (IRI); fat-1 transgenic mice; AMP-activated protein kinase (AMPK); autophagy ischemia-reperfusion injury (IRI); fat-1 transgenic mice; AMP-activated protein kinase (AMPK); autophagy
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MDPI and ACS Style

Gwon, D.H.; Hwang, T.W.; Ro, J.-Y.; Kang, Y.-J.; Jeong, J.Y.; Kim, D.-K.; Lim, K.; Kim, D.W.; Choi, D.E.; Kim, J.-J. High Endogenous Accumulation of ω-3 Polyunsaturated Fatty Acids Protect against Ischemia-Reperfusion Renal Injury through AMPK-Mediated Autophagy in Fat-1 Mice. Int. J. Mol. Sci. 2017, 18, 2081. https://doi.org/10.3390/ijms18102081

AMA Style

Gwon DH, Hwang TW, Ro J-Y, Kang Y-J, Jeong JY, Kim D-K, Lim K, Kim DW, Choi DE, Kim J-J. High Endogenous Accumulation of ω-3 Polyunsaturated Fatty Acids Protect against Ischemia-Reperfusion Renal Injury through AMPK-Mediated Autophagy in Fat-1 Mice. International Journal of Molecular Sciences. 2017; 18(10):2081. https://doi.org/10.3390/ijms18102081

Chicago/Turabian Style

Gwon, Do Hyeong, Tae Woong Hwang, Ju-Ye Ro, Yoon-Joong Kang, Jin Young Jeong, Do-Kyung Kim, Kyu Lim, Dong Woon Kim, Dae Eun Choi, and Jwa-Jin Kim. 2017. "High Endogenous Accumulation of ω-3 Polyunsaturated Fatty Acids Protect against Ischemia-Reperfusion Renal Injury through AMPK-Mediated Autophagy in Fat-1 Mice" International Journal of Molecular Sciences 18, no. 10: 2081. https://doi.org/10.3390/ijms18102081

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