摘要
背景:非酒精性脂肪性肝病(NAFLD)的特征是在没有饮酒的情况下肝甘油三酸酯的异常蓄积,并伴有氧化应激(OS),促炎状态和胰岛素抵抗(IR),其被衰减n -3长链多不饱和脂肪酸(FA)C20-C22(LCPUFAs)补充。 NAFLD的主要原因包括高热量摄入和久坐不动的生活方式,以及高摄入饱和脂肪酸。 方法:这篇综述使用了美国国立卫生研究院国家医学图书馆的PubMed数据库,考虑了n-3 LCPUFAs在NAFLD体内和体外模型中的作用,进行了多次检索。 结果:LCPUFAs二十碳五烯酸(C20:5 n-3,EPA)和二十二碳六烯酸(C22:6 n-3,DHA)在减少肝脏脂肪变性,OS以及天冬氨酸转氨酶,丙氨酸转氨酶和脯氨酸水平方面均具有积极作用炎症细胞因子,改善胰岛素敏感性和脂联素水平。 在细胞和动物模型以及人类中,n-3 LCPUFAs的分子途径包括过氧化物酶体增殖物激活的受体α活化,促进FA氧化,由于固醇响应元件结合蛋白1c下调和脂肪消融而导致的脂肪生成减少。 此外,n-3 LCPUFA衍生的氧化产物可引发核因子红系2相关因子2活化,产生直接和间接的抗氧化反应,并伴有抗纤维化作用。 结论:讨论的n-3 LCPUFA补充剂的作用支持其在NAFLD中的使用,尽管在NASH中具有有限的价值,这一争端可能涉及n-3 LCPUFA含氧衍生物。 未来的研究需要确定最佳剂量,干预时间,患者类型以及与其他天然产物可能的协同作用的临床试验。
关键词: 肝脂肪变性,n-3多不饱和脂肪酸,α-亚麻酸,二十碳五烯酸,二十二碳六烯酸,抗脂生机制
[http://dx.doi.org/10.1002/hep.29721] [PMID: 29222917]
[http://dx.doi.org/10.5306/wjco.v8.i6.429] [PMID: 29291167]
[http://dx.doi.org/10.1111/dme.13565] [PMID: 29247558]
[http://dx.doi.org/10.1042/CS20030326] [PMID: 14720121]
[http://dx.doi.org/10.1016/j.plipres.2011.06.003] [PMID: 21762726]
[http://dx.doi.org/10.1016/j.plipres.2009.07.002] [PMID: 19619583]
[http://dx.doi.org/10.1016/j.plefa.2016.02.002] [PMID: 26995676]
[http://dx.doi.org/10.1016/j.bbalip.2016.05.014] [PMID: 27263420]
[http://dx.doi.org/10.1146/annurev.nutr.24.121803.063211] [PMID: 15189125]
[http://dx.doi.org/10.1016/j.plefa.2015.04.002] [PMID: 25910408]
[http://dx.doi.org/10.1186/s12944-017-0450-5] [PMID: 28395666]
[http://dx.doi.org/10.1016/j.nut.2017.07.007] [PMID: 29129237]
[http://dx.doi.org/10.1016/j.plefa.2010.02.015] [PMID: 20226642]
[http://dx.doi.org/10.1016/j.nut.2016.04.006] [PMID: 27346714]
[http://dx.doi.org/10.1155/2012/107434] [PMID: 23304111]
[http://dx.doi.org/10.1210/jc.2010-2129] [PMID: 21325464]
[http://dx.doi.org/10.1002/hep.29246] [PMID: 28470676]
[http://dx.doi.org/10.1016/j.plipres.2010.05.003] [PMID: 20553760]
[http://dx.doi.org/10.1016/j.freeradbiomed.2004.06.033] [PMID: 15454290]
[http://dx.doi.org/10.1371/journal.pone.0046400] [PMID: 23082120]
[http://dx.doi.org/10.1016/j.plefa.2016.10.001] [PMID: 27926461]
[http://dx.doi.org/10.1172/JCI0215593] [PMID: 11994399]
[http://dx.doi.org/10.1016/j.plefa.2009.05.020] [PMID: 19540099]
[http://dx.doi.org/10.1039/C5FO01086A] [PMID: 26471014]
[http://dx.doi.org/10.1016/j.jada.2011.10.007] [PMID: 22717200]
[http://dx.doi.org/10.1016/j.jand.2014.01.009] [PMID: 24631112]
[http://dx.doi.org/10.5812/hepatmon.10939] [PMID: 24693306]
[http://dx.doi.org/10.1111/j.1365-2036.2009.04230.x] [PMID: 20415840]
[http://dx.doi.org/10.1016/j.jhep.2007.06.020] [PMID: 17850914]
[http://dx.doi.org/10.3390/nu6114691] [PMID: 25353664]
[http://dx.doi.org/10.1038/oby.2009.379] [PMID: 19875987]
[http://dx.doi.org/10.3390/nu9090981] [PMID: 28878197]
[http://dx.doi.org/10.1016/j.jhep.2008.02.011] [PMID: 18395287]
[http://dx.doi.org/10.1186/s12986-015-0038-x] [PMID: 26583036]
[http://dx.doi.org/10.3390/md13041864] [PMID: 25837985]
[http://dx.doi.org/10.1016/j.toxlet.2012.06.002] [PMID: 22698815]
[http://dx.doi.org/10.1089/ars.2014.5868] [PMID: 25602171]
[http://dx.doi.org/10.1016/j.jhep.2004.07.002] [PMID: 15519643]
[http://dx.doi.org/10.1053/j.gastro.2009.01.048] [PMID: 19208352]
[http://dx.doi.org/10.1016/j.jnutbio.2012.03.004] [PMID: 22749135]
[http://dx.doi.org/10.1016/j.clnu.2006.01.027] [PMID: 16677739]
[http://dx.doi.org/10.1093/ajcn/86.2.285] [PMID: 17684197]
[http://dx.doi.org/10.1371/journal.pone.0091436] [PMID: 24638096]
[http://dx.doi.org/10.1016/j.clnu.2010.06.001] [PMID: 20619513]
[http://dx.doi.org/10.3945/ajcn.110.006643] [PMID: 21367944]
[http://dx.doi.org/10.1155/2012/539426] [PMID: 22570770]
[http://dx.doi.org/10.1371/journal.pone.0023365] [PMID: 21853118]
[http://dx.doi.org/10.3390/nu5082901] [PMID: 23896654]
[http://dx.doi.org/10.1038/ejcn.2010.35] [PMID: 20216561]
[http://dx.doi.org/10.1097/MPG.0b013e3182a1df77] [PMID: 24177784]
[http://dx.doi.org/10.3748/wjg.v16.i7.800]] [PMID: 20143458]
[http://dx.doi.org/10.3748/wjg.v20.i7.1746] [PMID: 24587652]
[http://dx.doi.org/10.1017/S0007114508027451] [PMID: 18710604]
[http://dx.doi.org/10.3390/ijms18122645] [PMID: 29215589]
[http://dx.doi.org/10.1016/j.molmed.2006.10.001] [PMID: 17049925]
[http://dx.doi.org/10.2337/diabetes.50.8.1844] [PMID: 11473047]
[http://dx.doi.org/10.1053/j.gastro.2011.06.061] [PMID: 21726509]
[http://dx.doi.org/10.1194/jlr.R008896] [PMID: 21245030]
[http://dx.doi.org/10.2174/138161210791208875] [PMID: 20370677]
[http://dx.doi.org/10.1039/c1fo10133a] [PMID: 22008843]
[http://dx.doi.org/10.1016/j.freeradbiomed.2015.09.004] [PMID: 26434419]
[http://dx.doi.org/10.1155/2007/95974] [PMID: 17389767]
[http://dx.doi.org/10.1016/j.tips.2005.03.003] [PMID: 15860371]
[http://dx.doi.org/10.4254/wjh.v7.i8.1012] [PMID: 26052390]
[http://dx.doi.org/10.1371/journal.pone.0028502] [PMID: 22174823]
[http://dx.doi.org/10.1161/01.CIR.99.24.3125] [PMID: 10377075]
[http://dx.doi.org/10.1016/j.bcp.2006.04.011] [PMID: 16723122]
[http://dx.doi.org/10.1038/oby.2008.601] [PMID: 19165171]
[http://dx.doi.org/10.1016/j.bbadis.2009.08.015] [PMID: 19733654]
[http://dx.doi.org/10.1016/j.clnu.2010.03.006] [PMID: 20403650]
[http://dx.doi.org/10.1016/j.bbalip.2011.10.016] [PMID: 22056763]
[http://dx.doi.org/10.1016/j.tips.2013.04.005] [PMID: 23664668]
[http://dx.doi.org/10.1074/jbc.M607622200] [PMID: 17127771]
[http://dx.doi.org/10.1007/BF02535573] [PMID: 1487958]
[http://dx.doi.org/10.1152/ajpgi.00296.2009] [PMID: 19926817]
[http://dx.doi.org/10.1089/ars.2010.3216] [PMID: 20367496]
[http://dx.doi.org/10.4049/jimmunol.179.11.7840] [PMID: 18025230]
[http://dx.doi.org/10.1016/j.jnutbio.2015.02.001] [PMID: 25841249]
[http://dx.doi.org/10.1016/j.amjcard.2016.10.027] [PMID: 27939227]
[http://dx.doi.org/10.1016/j.plefa.2017.08.001] [PMID: 28870371]
[http://dx.doi.org/10.1002/mnfr.201300458] [PMID: 24436018]
[http://dx.doi.org/10.1002/mnfr.201700479] [PMID: 28940752]
[http://dx.doi.org/10.1016/j.bbalip.2015.08.007] [PMID: 26327595]
[http://dx.doi.org/10.1258/ebm.2010.009298] [PMID: 20558833]
[http://dx.doi.org/10.1093/advances/nmy007] [PMID: 29767698]
[http://dx.doi.org/10.1152/ajpendo.00644.2005] [PMID: 16492686]
[http://dx.doi.org/10.4254/wjh.v2.i6.203] [PMID: 21160998]
[http://dx.doi.org/10.1016/j.plipres.2012.10.004] [PMID: 23178552]
[http://dx.doi.org/10.1186/1476-511X-10-122] [PMID: 21787405]
[http://dx.doi.org/10.1042/CS20030285] [PMID: 14556645]
[http://dx.doi.org/10.1074/jbc.M411860200] [PMID: 15509553]
[http://dx.doi.org/10.1186/s12986-017-0209-z] [PMID: 28811832]
[http://dx.doi.org/10.1016/j.jhep.2010.07.039] [PMID: 21093950]
[http://dx.doi.org/10.1203/01.PDR.0000153672.43030.75] [PMID: 15659701]
[http://dx.doi.org/10.1096/fj.08-125674] [PMID: 19211925]
[http://dx.doi.org/10.1016/j.jhep.2008.10.031] [PMID: 19162361]
[http://dx.doi.org/10.2353/ajpath.2006.050953] [PMID: 16936261]
[PMID: 24322028]
[http://dx.doi.org/10.1007/s11745-014-3892-9] [PMID: 24627299]
[http://dx.doi.org/10.1111/j.1440-1746.2007.05157.x] [PMID: 17868330]
[http://dx.doi.org/10.1016/j.jnutbio.2014.04.011] [PMID: 24993917]
[http://dx.doi.org/10.3892/ijmm.18.6.1047] [PMID: 17089007]
[http://dx.doi.org/10.1186/1472-6793-8-21] [PMID: 19046413]
[http://dx.doi.org/10.1038/427504a] [PMID: 14765186]
[http://dx.doi.org/10.1016/j.bcp.2012.08.029] [PMID: 22981383]
[http://dx.doi.org/10.1371/journal.pone.0083756] [PMID: 24358308]
[http://dx.doi.org/10.1073/pnas.1422590112] [PMID: 25550510]
[http://dx.doi.org/10.1111/bph.13844] [PMID: 28471490]
[http://dx.doi.org/10.1016/j.plefa.2013.09.009] [PMID: 24140006]
[http://dx.doi.org/10.1039/C3FO60688K] [PMID: 24855655]
[http://dx.doi.org/10.3945/jn.116.243261] [PMID: 28298541]
[http://dx.doi.org/10.1039/C6FO01762B] [PMID: 28128380]
[http://dx.doi.org/10.1039/C5FO00741K] [PMID: 26218006]
[http://dx.doi.org/10.1139/cjpp-2012-0308] [PMID: 23746194]
[http://dx.doi.org/10.1016/j.bbalip.2009.01.014]] [PMID: 19416647 ]
[http://dx.doi.org/10.1371/journal.pone.0121528] [PMID: 25816330]
[http://dx.doi.org/10.1038/srep30029] [PMID: 27435808]
[http://dx.doi.org/10.1016/j.ejbas.2014.12.005]
[http://dx.doi.org/10.1590/abd1806-4841.20176198] [PMID: 28538876]
[http://dx.doi.org/10.1016/j.toxlet.2013.05.644] [PMID: 23747427]
[http://dx.doi.org/10.1016/j.cell.2010.07.041] [PMID: 20813258]
[http://dx.doi.org/10.1042/CS20080253] [PMID: 19243311]
[http://dx.doi.org/10.1111/j.1365-2036.2006.02885.x] [PMID: 16611275]
[http://dx.doi.org/10.3748/wjg.14.6395] [PMID: 19009658]
[http://dx.doi.org/10.1016/j.dld.2007.10.003] [PMID: 18054848]
[http://dx.doi.org/10.3109/09637486.2010.487480] [PMID: 20465434]
[http://dx.doi.org/10.1038/ejcn.2010.139] [PMID: 20683463]
[http://dx.doi.org/10.1097/MCG.0b013e31815591aa] [PMID: 18277895]
[http://dx.doi.org/10.1016/j.jhep.2011.08.018] [PMID: 22023985]
[http://dx.doi.org/10.1016/j.jhep.2012.01.028] [PMID: 22433603]
[http://dx.doi.org/10.1016/S0140-6736(99)07072-5] [PMID: 10465168]
[http://dx.doi.org/10.1016/S0140-6736(10)60445-X] [PMID: 20638121]
[http://dx.doi.org/10.1016/j.clnu.2011.12.007] [PMID: 22209679]
[http://dx.doi.org/10.1002/hep.27289] [PMID: 25043514]
[http://dx.doi.org/10.3748/wjg.v21.i22.7008] [PMID: 26078579]
[http://dx.doi.org/10.1016/j.numecd.2012.10.010] [PMID: 23220074]
[http://dx.doi.org/10.1016/j.nut.2014.03.020] [PMID: 25280409]
[http://dx.doi.org/10.1016/j.nut.2011.01.004] [PMID: 21658909]
[http://dx.doi.org/10.1016/j.jpeds.2015.01.056] [PMID: 25771388]
[http://dx.doi.org/10.1016/j.jhep.2014.08.036] [PMID: 25195547]
[http://dx.doi.org/10.1097/MCG.0000000000000099] [PMID: 24583757]
[http://dx.doi.org/10.1053/j.gastro.2014.04.046] [PMID: 24818764]
[http://dx.doi.org/10.3748/wjg.v18.i41.5839] [PMID: 23139599]
[http://dx.doi.org/10.1016/j.pharmthera.2017.07.007] [PMID: 28723414]
[http://dx.doi.org/10.1016/j.mam.2018.03.001] [PMID: 29544992 ]
[http://dx.doi.org/10.1371/journal.pone.0162368] [PMID: 27711128]
[http://dx.doi.org/10.1038/s41575-018-0009-6] [PMID: 29740166]
[http://dx.doi.org/10.1152/ajpendo.00366.2014] [PMID: 25389366]
[http://dx.doi.org/10.1371/journal.pone.0110162] [PMID: 25310404]
[http://dx.doi.org/10.1016/j.phrs.2017.12.013] [PMID: 29253525]
[http://dx.doi.org/10.1089/ars.2016.6776] [PMID: 27452109]
[http://dx.doi.org/10.1155/2018/9547613] [PMID: 29991976]