What we need to know about lipid-associated injury in case of renal ischemia/reperfusion.

[en] Renal segmental metabolism is reflected by the complex distribution of the main energy pathways along the nephron, with fatty acid oxidation preferentially used in the cortex area. Ischemia/reperfusion injury (IRI) is due to the restriction of renal blood flow, rapidly leading to a metabolic switch towards anaerobic conditions. Subsequent unbalance between energy demand and oxygen/nutrient delivery compromises kidney cell functions, resulting to a complex inflammatory cascade including the production of reactive oxygen species (ROS). Renal IRI especially involves lipid accumulation. Lipid peroxidation is one of the major events of ROS-associated tissue injury. Here, we briefly review the current knowledge of renal cell lipid metabolism in normal and ischemic conditions. Next, we focus on renal lipid-associated injury, with emphasis on its mechanisms and consequences during the course of IRI. Finally, we discuss preclinical observations aiming at preventing and/or attenuating lipid-associated IRI.

Disciplines :

Urology & nephrology

Author, co-author :

ERPICUM, Pauline ; Département de médecine interne > Service de néphrologie

Rowart, Pascal ; Université de Liège - ULiège > Département des sciences cliniques > Néphrologie

Defraigne, Jean-Olivier ; Université de Liège - ULiège > Département des sciences cliniques > Chirurgie cardio-vasculaire et thoracique

Krzesinski, Jean-Marie ; Université de Liège - ULiège > Département des sciences cliniques > Néphrologie

Jouret, François ; Université de Liège - ULiège > Département des sciences cliniques > Néphrologie

Language :

English

Title :

What we need to know about lipid-associated injury in case of renal ischemia/reperfusion.

Publication date :

2018

Journal title :

American Journal of Physiology. Renal Physiology

ISSN :

1931-857X

eISSN :

1522-1466

Publisher :

American Physiological Society, Bethesda, United States - Maryland

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 19 November 2018

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Bibliography

Friedmann Angeli JP, Schneider M, Proneth B, Tyurina YY, Tyurin VA, Hammond VJ, Herbach N, Aichler M, Walch A, Eggenhofer E, Basavarajappa D, Rådmark O, Kobayashi S, Seibt T, Beck H, Neff F, Esposito I, Wanke R, Förster H, Yefremova O, Heinrichmeyer M, Bornkamm GW, Geissler EK, Thomas SB, Stockwell BR, O’Donnell VB, Kagan VE, Schick JA, Conrad M. Inactivation of the ferroptosis regulator Gpx4 triggers acute renal failure in mice. Nat Cell Biol 16: 1180–1191, 2014. doi:10.1038/ncb3064.
Avunduk MC, Yurdakul T, Erdemli E, Yavuz A. Prevention of renal damage by alpha tocopherol in ischemia and reperfusion models of rats. Urol Res 31: 280–285, 2003. doi:10.1007/s00240-003-0329-y.
Bernardi P, Penzo D, Wojtczak L. Mitochondrial energy dissipation by fatty acids. Mechanisms and implications for cell death. Vitam Horm 65: 97–126, 2002. doi:10.1016/S0083-6729(02)65061-7.
Bobulescu IA. Renal lipid metabolism and lipotoxicity. Curr Opin Nephrol Hypertens 19: 393–402, 2010. doi:10.1097/MNH.0b013e32833aa4ac.
Chatterjee PK, Cuzzocrea S, Brown PAJ, Zacharowski K, Stewart KN, Mota-Filipe H, Thiemermann C. Tempol, a membrane-permeable radical scavenger, reduces oxidant stress-mediated renal dysfunction and injury in the rat. Kidney Int 58: 658–673, 2000. doi:10.1046/j.1523-1755. 2000.00212.x.
Cheeseman KH. Mechanisms and effects of lipid peroxidation. Mol Aspects Med 14: 191–197, 1993. doi:10.1016/0098-2997(93)90005-X.
Ergün O, Ulman C, Kiliçalp AS, Ulman I. Carnitine as a preventive agent in experimental renal ischemia-reperfusion injury. Urol Res 29: 186–189, 2001. doi:10.1007/s002400100176.
Erpicum P, Rowart P, Poma L, Krzesinski J-M, Detry O, Jouret F. Administration of mesenchymal stromal cells before renal ischemia/ reperfusion attenuates kidney injury and may modulate renal lipid metabolism in rats. Sci Rep 7: 8687, 2017. doi:10.1038/s41598-017-08726-z.
Feldkamp T, Kribben A, Roeser NF, Ostrowski T, Weinberg JM. Alleviation of fatty acid and hypoxia-reoxygenation-induced proximal tubule deenergization by ADP/ATP carrier inhibition and glutamate. Am J Physiol Renal Physiol 292: F1606–F1616, 2007. doi:10.1152/ajprenal. 00476.2006.
Feldkamp T, Kribben A, Roeser NF, Senter RA, Weinberg JM. Accumulation of nonesterified fatty acids causes the sustained energetic deficit in kidney proximal tubules after hypoxia-reoxygenation. Am J Physiol Renal Physiol 290: F465–F477, 2006. doi:10.1152/ajprenal. 00305.2005.
Feldkamp T, Park JS, Pasupulati R, Amora D, Roeser NF, Venkatachalam MA, Weinberg JM. Regulation of the mitochondrial permeability transition in kidney proximal tubules and its alteration during hypoxia-reoxygenation. Am J Physiol Renal Physiol 297: F1632–F1646, 2009. doi:10.1152/ajprenal.00422.2009.
Feldkamp T, Weinberg JM, Hörbelt M, Von Kropff C, Witzke O, Nürnberger J, Kribben A. Evidence for involvement of nonesterified fatty acid-induced protonophoric uncoupling during mitochondrial dysfunction caused by hypoxia and reoxygenation. Nephrol Dial Transplant 24: 43–51, 2009. doi:10.1093/ndt/gfn436.
Feng H, Stockwell BR. Unsolved mysteries: How does lipid peroxidation cause ferroptosis? PLoS Biol 16: e2006203, 2018. doi:10.1371/journal. pbio.2006203.
Finkelstein SD, Gilfor D, Farber JL. Alterations in the metabolism of lipids in ischemia of the liver and kidney. J Lipid Res 26: 726–734, 1985.
Gailly P, Jouret F, Martin D, Debaix H, Parreira KS, Nishita T, Blanchard A, Antignac C, Willnow TE, Courtoy PJ, Scheinman SJ, Christensen EI, Devuyst O. A novel renal carbonic anhydrase type III plays a role in proximal tubule dysfunction. Kidney Int 74: 52–61, 2008. doi:10.1038/sj.ki.5002794.
Görür S, Bağdatoğlu OT, Polat G. Protective effect of L-carnitine on renal ischaemia-reperfusion injury in the rat. Cell Biochem Funct 23: 151–155, 2005. doi:10.1002/cbf.1159.
Green CJ, Healing G, Simpkin S, Lunec J, Fuller BJ. Desferrioxamine reduces susceptibility to lipid peroxidation in rabbit kidneys subjected to warm ischaemia and reperfusion. Comp Biochem Physiol B 85: 113–117, 1986. doi:10.1016/0305-0491(86)90230-0.
Guan Y, Breyer MD. Peroxisome proliferator-activated receptors (PPARs): novel therapeutic targets in renal disease. Kidney Int 60: 14–30, 2001. doi:10.1046/j.1523-1755.2001.00766.x.
Guder WG, Wagner S, Wirthensohn G. Metabolic fuels along the nephron: pathways and intracellular mechanisms of interaction. Kidney Int 29: 41–45, 1986. doi:10.1038/ki.1986.6.
Guebre-Egziabher F, Alix PM, Koppe L, Pelletier CC, Kalbacher E, Fouque D, Soulage CO. Ectopic lipid accumulation: A potential cause for metabolic disturbances and a contributor to the alteration of kidney function. Biochimie 95: 1971–1979, 2013. doi:10.1016/j.biochi.2013.07. 017.
Gulati S, Ainol L, Orak J, Singh AK, Singh I. Alterations of peroxi-somal function in ischemia-reperfusion injury of rat kidney. Biochim Biophys Acta 1182: 291–298, 1993. doi:10.1016/0925-4439(93)90071-8.
Hajri T, Abumrad NA. Fatty acid transport across membranes: relevance to nutrition and metabolic pathology. Annu Rev Nutr 22: 383–415, 2002. doi:10.1146/annurev.nutr.22.020402.130846.
Hauck AK, Bernlohr DA. Oxidative stress and lipotoxicity. J Lipid Res 57: 1976–1986, 2016. doi:10.1194/jlr.R066597.
Idrovo J-P, Yang W-L, Matsuda A, Nicastro J, Coppa GF, Wang P. Post-treatment with the combination of 5-aminoimidazole-4-carboxy-amide ribonucleoside and carnitine improves renal function after ischemia-reperfusion injury. Shock 37: 39–46, 2012. doi:10.1097/SHK. 0b013e31823185d7.
Idrovo J-P, Yang W-L, Nicastro J, Coppa GF, Wang P. Stimulation of carnitine palmitoyltransferase 1 improves renal function and attenuates tissue damage after ischemia/reperfusion. J Surg Res 177: 157–164, 2012. doi:10.1016/j.jss.2012.05.053.
Inoguchi T, Li P, Umeda F, Yu HY, Kakimoto M, Imamura M, Aoki T, Etoh T, Hashimoto T, Naruse M, Sano H, Utsumi H, Nawata H. High glucose level and free fatty acid stimulate reactive oxygen species production through protein kinase C-dependent activation of NAD(P)H oxidase in cultured vascular cells. Diabetes 49: 1939–1945, 2000. doi:10. 2337/diabetes.49.11.1939.
Johnson ALICM, Stahl A, Zager RA. Triglyceride accumulation in injured renal tubular cells: alterations in both synthetic and catabolic pathways. Kidney Int 67: 2196–2209, 2005. doi:10.1111/j.1523-1755. 2005.00325.x.
Jouret F, Leenders J, Poma L, Defraigne J-O, Krzesinski J-M, de Tullio P. Nuclear magnetic resonance metabolomic profiling of mouse kidney, urine and serum following renal ischemia/reperfusion injury. PLoS One 11: e0163021, 2016. doi:10.1371/journal.pone.0163021.
Kang HM, Ahn SH, Choi P, Ko Y-A, Han SH, Chinga F, Park ASD, Tao J, Sharma K, Pullman J, Bottinger EP, Goldberg IJ, Susztak K, Seo A, Park D, Tao J, Sharma K, Pullman J, Bottinger EP, Goldberg IJ, Susztak K. Defective fatty acid oxidation in renal tubular epithelial cells has a key role in kidney fibrosis development. Nat Med 21: 37–46, 2015. doi:10.1038/nm.3762.
Katsoulieris E, Mabley JG, Samai M, Sharpe MA, Green IC, Chatterjee PK. Lipotoxicity in renal proximal tubular cells: relationship between endoplasmic reticulum stress and oxidative stress pathways. Free Radic Biol Med 48: 1654–1662, 2010. doi:10.1016/j.freeradbiomed.2010. 03.021.
Kim J, Jung K-J, Park KM. Reactive oxygen species differently regulate renal tubular epithelial and interstitial cell proliferation after ischemia and reperfusion injury. Am J Physiol Renal Physiol 298: F1118–F1129, 2010. doi:10.1152/ajprenal.00701.2009.
Li S, Nagothu KK, Desai V, Lee T, Branham W, Moland C, Megyesi JK, Crew MD, Portilla D. Transgenic expression of proximal tubule peroxisome proliferator-activated receptor-± in mice confers protection during acute kidney injury. Kidney Int 76: 1049–1062, 2009. doi:10.1038/ki.2009.330.
Linkermann A, Skouta R, Himmerkus N, Mulay SR, Dewitz C, De Zen F, Prokai A, Zuchtriegel G, Krombach F, Welz P-S, Weinlich R, Vanden Berghe T, Vandenabeele P, Pasparakis M, Bleich M, Weinberg JM, Reichel CA, Bräsen JH, Kunzendorf U, Anders HJ, Stockwell BR, Green DR, Krautwald S. Synchronized renal tubular cell death involves ferroptosis. Proc Natl Acad Sci USA 111: 16836–16841, 2014. doi:10.1073/pnas.1415518111.
Listenberger LL, Han X, Lewis SE, Cases S, Farese RV Jr, Ory DS, Schaffer JE. Triglyceride accumulation protects against fatty acid-induced lipotoxicity. Proc Natl Acad Sci USA 100: 3077–3082, 2003. doi:10.1073/pnas.0630588100.
Liu Y, Yan S, Ji C, Dai W, Hu W, Zhang W, Mei C. Metabolomic changes and protective effect of (L)-carnitine in rat kidney ischemia/ reperfusion injury. Kidney Blood Press Res 35: 373–381, 2012. doi:10. 1159/000336171.
Lopez-Hernandez FJ, Lopez-Novoa JM. Potential utility of PPARalpha activation in the prevention of ischemic and drug-induced acute renal damage. Kidney Int 76: 1022–1024, 2009. doi:10.1038/ki.2009.229.
Matthys E, Patel Y, Kreisberg J, Stewart JH, Venkatachalam M. Lipid alterations induced by renal ischemia: pathogenic factor in membrane damage. Kidney Int 26: 153–161, 1984. doi:10.1038/ki.1984.149.
Mister M, Noris M, Szymczuk J, Azzollini N, Aiello S, Abbate M, Trochimowicz L, Gagliardini E, Arduini A, Perico N, Remuzzi G. Propionyl-L-carnitine prevents renal function deterioration due to ischemia/reperfusion. Kidney Int 61: 1064–1078, 2002. doi:10.1046/j.1523-1755.2002.00212.x.
Müller T, Dewitz C, Schmitz J, Schröder AS, Bräsen JH, Stockwell BR, Murphy JM, Kunzendorf U, Krautwald S. Necroptosis and ferroptosis are alternative cell death pathways that operate in acute kidney failure. Cell Mol Life Sci 74: 3631–3645, 2017. doi:10.1007/s00018-017-2547-4.
Mylonas C, Kouretas D. Lipid peroxidation and tissue damage. In Vivo 13: 295–309, 1999.
Nakamura H, Nemenoff RA, Gronich JH, Bonventre JV. Subcellular characteristics of phospholipase A2 activity in the rat kidney. Enhanced cytosolic, mitochondrial, and microsomal phospholipase A2 enzymatic activity after renal ischemia and reperfusion. J Clin Invest 87: 1810–1818, 1991. doi:10.1172/JCI115202.
Paller MS, Hedlund BE. Role of iron in postischemic renal injury in the rat. Kidney Int 34: 474–480, 1988. doi:10.1038/ki.1988.205.
Park JS, Pasupulati R, Feldkamp T, Roeser NF, Weinberg JM. Cyclophilin D and the mitochondrial permeability transition in kidney proximal tubules after hypoxic and ischemic injury. Am J Physiol Renal Physiol 301: F134–F150, 2011. doi:10.1152/ajprenal.00033.2011.
Patel NS, di Paola R, Mazzon E, Britti D, Thiemermann C, Cuzzocrea S. Peroxisome proliferator-activated receptor-± contributes to the resolution of inflammation after renal ischemia/reperfusion injury. J Pharmacol Exp Ther 328: 635–643, 2009. doi:10.1124/jpet.108.146191.
Portilla D, Dai G, Peters JM, Gonzalez FJ, Crew MD, Proia AD. Etomoxir-induced PPAR±-modulated enzymes protect during acute renal failure. Am J Physiol Renal Physiol 278: F667–F675, 2000. doi:10.1152/ajprenal.2000.278.4.F667.
Ruidera E, Irazu CE, Rajagopalan PR, Orak JK, Fitts CT, Singh I. Fatty acid metabolism in renal ischemia. Lipids 23: 882–884, 1988. doi:10.1007/BF02536209.
Scerbo D, Son N-H, Sirwi A, Zeng L, Sas KM, Cifarelli V, Schoiswohl G, Huggins L-A, Gumaste N, Hu Y, Pennathur S, Abumrad NA, Kershaw EE, Hussain MM, Susztak K, Goldberg IJ. Kidney triglyceride accumulation in the fasted mouse is dependent upon serum free fatty acids. J Lipid Res 58: 1132–1142, 2017 [Erratum in J Lipid Res 58: 1933, 2017]. doi:10.1194/jlr.M074427.
Schaffer JE. Lipotoxicity: when tissues overeat. Curr Opin Lipidol 14: 281–287, 2003. doi:10.1097/00041433-200306000-00008.
Schönfeld P, Wojtczak L. Fatty acids as modulators of the cellular production of reactive oxygen species. Free Radic Biol Med 45: 231–241, 2008. doi:10.1016/j.freeradbiomed.2008.04.029.
Seo-Mayer PW, Thulin G, Zhang L, Alves DS, Ardito T, Kashgarian M, Caplan MJ. Preactivation of AMPK by metformin may ameliorate the epithelial cell damage caused by renal ischemia. Am J Physiol Renal Physiol 301: F1346–F1357, 2011. doi:10.1152/ajprenal.00420.2010.
Simon N, Hertig A. Alteration of fatty acid oxidation in tubular epithelial cells: from acute kidney injury to renal fibrogenesis. Front Med (Laus-anne) 2: 52, 2015. doi:10.3389/fmed.2015.00052.
Sivarajah A, Chatterjee PK, Hattori Y, Brown PA, Stewart KN, Todorovic Z, Mota-Filipe H, Thiemermann C. Agonists of peroxisome-proliferator activated receptor-± (clofibrate and WY14643) reduce renal ischemia/reperfusion injury in the rat. Med Sci Monit 8: BR532–BR539, 2002.
Smith MW, Collan Y, Kahng MW, Trump BF. Changes in mitochondrial lipids of rat kidney during ischemia. Biochim Biophys Acta 618: 192–201, 1980. doi:10.1016/0005-2760(80)90025-9.
Stockwell BR, Friedmann Angeli JP, Bayir H, Bush AI, Conrad M, Dixon SJ, Fulda S, Gascón S, Hatzios SK, Kagan VE, Noel K, Jiang X, Linkermann A, Murphy ME, Overholtzer M, Oyagi A, Pagnussat GC, Park J, Ran Q, Rosenfeld CS, Salnikow K, Tang D, Torti FM, Torti SV, Toyokuni S, Woerpel KA, Zhang DD. Ferroptosis: a regulated cell death nexus linking metabolism, redox biology, and disease. Cell 171: 273–285, 2017. doi:10.1016/j.cell.2017.09.021.
Vasko R. Peroxisomes and kidney injury. Antioxid Redox Signal 25: 217–231, 2016. doi:10.1089/ars.2016.6666.
Wei Q, Xiao X, Fogle P, Dong Z. Changes in metabolic profiles during acute kidney injury and recovery following ischemia/reperfusion. PLoS One 9: e106647, 2014. doi:10.1371/journal.pone.0106647.
Weinberg JM. The cell biology of ischemic renal injury. Kidney Int 39: 476–500, 1991. doi:10.1038/ki.1991.58.
Weinberg JM. Lipotoxicity. Kidney Int 70: 1560–1566, 2006. doi:10. 1038/sj.ki.5001834.
Weinberg JM, Venkatachalam MA, Roeser NF, Saikumar P, Dong Z, Senter RA, Nissim I. Anaerobic and aerobic pathways for salvage of proximal tubules from hypoxia-induced mitochondrial injury. Am J Physiol Renal Physiol 279: F927–F943, 2000. doi:10.1152/ajprenal.2000. 279.5.F927.
Wetzels JF, Yu L, Wang X, Kribben A, Burke TJ, Schrier RW. Calcium modulation and cell injury in isolated rat proximal tubules. J Pharmacol Exp Ther 267: 176–180, 1993.
Wojtczak L, Wieckowski MR. The mechanisms of fatty acid-induced proton permeability of the inner mitochondrial membrane. J Bioenerg Biomembr 31: 447–455, 1999. doi:10.1023/A:1005444322823.
Zager RA. Hypoperfusion-induced acute renal failure in the rat: an evaluation of oxidant tissue injury. Circ Res 62: 430–435, 1988. doi:10. 1161/01.RES.62.3.430.
Zager RA, Johnson ACM, Becker K. Acute unilateral ischemic renal injury induces progressive renal inflammation, lipid accumulation, histone modification, and “end-stage” kidney disease. Am J Physiol Renal Physiol 301: F1334–F1345, 2011. doi:10.1152/ajprenal.00431.2011.
Zager RA, Burkhart KM, Johnson ACM, Sacks BM. Increased proximal tubular cholesterol content: implications for cell injury and “acquired cytoresistance”. Kidney Int 56: 1788–1797, 1999. doi:10.1046/j.1523-1755.1999.00745.x.
Zager RA, Conrad DS, Burkhart K. Phospholipase A2: a potentially important determinant of adenosine triphosphate levels during hypoxic-reoxygenation tubular injury. J Am Soc Nephrol 7: 2327–2339, 1996.
Zager RA, Johnson A, Anderson K. Plasma membrane cholesterol: a critical determinant of cellular energetics and tubular resistance to attack. Kidney Int 58: 193–205, 2000. doi:10.1046/j.1523-1755.2000.00154.x.
Zager RA, Johnson A, Anderson K, Wright S. Cholesterol ester accumulation: an immediate consequence of acute in vivo ischemic renal injury. Kidney Int 59: 1750–1761, 2001. doi:10.1046/j.1523-1755.2001. 0590051750.x.
Zager RA, Johnson ACM, Hanson SY. Renal tubular triglyercide accumulation following endotoxic, toxic, and ischemic injury. Kidney Int 67: 111–121, 2005. doi:10.1111/j.1523-1755.2005.00061.x.
Zager RA, Sacks BM, Burkhart KM, Williams AC. Plasma membrane phospholipid integrity and orientation during hypoxic and toxic proximal tubular attack. Kidney Int 56: 104–117, 1999. doi:10.1046/j.1523-1755. 1999.00533.x.
Zhou Y, Du D, Liu S, Zhao M, Yuan Y, Li L, Chen Y, Lu Y, Cheng J, Liu J. Polyacetylene glycoside attenuates ischemic kidney injury by co-inhibiting inflammation, mitochondria dysfunction and lipotoxicity. Life Sci 204: 55–64, 2018. doi:10.1016/j.lfs.2018.05.009.