高脂喂养及罗格列酮干预对老年大鼠骨骼肌线粒体功能的影响

目的 观察高脂饮食和罗格列酮干预对老年大鼠骨骼肌过氧化物酶体增生物激活受体γ共激活因子1α(PGC-1α)和线粒体融合蛋白2(Mfn2)表达的影响. 方法 21～23月龄Wistar大鼠分为老年对照组、高脂组和高脂+罗格列酮干预组(干预组),并设4～5月龄Wistar大鼠作为青年对照组.应用正常葡萄糖高胰岛素钳夹技术评价胰岛素敏感性,高脂喂养第8周时,检测骨骼肌PGC-1α和Mfn2的mRNA及蛋白表达.结果高脂喂养8周后,青年对照组、老年对照组和高脂组空腹血游离脂肪酸[(0.68±0.18)mmol/L、(0.82±0.23)mmol/L和(1.53±0.40)mmol/L],三酰甘油[(0.53±0.13)mmol/L、(0.63±0.17)mmol/L和(1.08±0.30)mmol/L],骨骼肌三酰甘油[(1.09±0.17)mmol/L、(1.34±0.20)mmol/L和(2.07±0.30)mmol/L]均升高,葡萄糖输注率((30.4±4.2)mg·kg~(-1)·min~(-1)、(20.9±2.2)mg·kg~(-1)·min~(-1)和(12.0±1.9)mg·kg~(-1)·min~(-1)]下降;经过罗格列酮干预后游离脂肪酸[(0.93±0.29)mmol/L]、三酰甘油[(0.62±0.12)mmol/L]及骨骼肌三酰甘油[(1.68±0.28)mmol/L)]均明显下降,葡萄糖输注率[(16.7±1.7)mg·kg~(-1)·min~(-1)]升高.与青年对照组比较,老年对照组骨骼肌PGC-1α和Mfn2的表达下降,经高脂喂养后PGc-1α和Mfn2的表达进一步下降,干预组上述基因的表达均显著高于高脂组(P<0.05),但仍比老年对照组降低(P<0.05). 结论 高脂饮食可诱导老年大鼠产生IR,推测可能与骨骼肌PGC-1α和Mfn2的表达下降有关;罗格列酮可通过改变骨骼肌PGC-1α和Mfn2的表达增加胰岛素敏感性.     

高脂喂养及罗格列酮干预对老年大鼠骨骼肌核呼吸因子1表达的影响

目的 观察高脂饮食和罗格列酮干预对老年大鼠骨骼肌核呼吸因子1(NRF-1)表达及葡萄糖输注率的影响.方法 21～23月龄Wistar大鼠分为老年对照组、高脂组和高脂+罗格列酮干预组(干预组),并设 4～5月龄Wistar大鼠作为青年对照组.应用正常葡萄糖高胰岛素钳夹技术测得葡萄糖输注率,以评价胰岛素敏感性,高脂喂养第8周时,检测骨骼肌NRF-1 mRNA表达.结果 高脂喂养8 w后青年对照组、老年对照组和高脂组空腹血游离脂肪酸、三酰甘油及骨骼肌三酰甘油均升高,葡萄糖输注率下降;经过罗格列酮干预后上述三组游离脂肪酸、三酰甘油及骨骼肌三酰甘油均明显下降,葡萄糖输注率升高.与青年对照组比较,老年对照组骨骼肌NRF-1的表达下降,经高脂喂养后NRF-1的表达进一步下降,干预组NRF-1表达高于高脂组(P<0.01),但仍比老年对照组的表达低(P<0.01).结论 高脂饮食可诱导老年大鼠产生IR及骨骼肌 NRF-1表达下降,罗格列酮可能调节骨骼肌NRF-1的表达.     

罗格列酮对大鼠动脉粥样硬化斑块形成的影响

目的探讨罗格列酮对大鼠动脉粥样硬化(AS)斑块的作用及可能机制。方法12周龄雄性Wistar大鼠55只,随机分为对照组20只、模型组20只、治疗组15只。对照组大鼠喂食基础饲料;模型组和治疗组在喂食开始时一次性腹腔注射维生素D_3 40万IU/kg,喂食高脂饲料。6周后,处死对照组和模型组大鼠各5只,提取全长主动脉,油红O染色进行病变分级评分;HE染色观察斑块的病理形态改变;免疫组化法测定过氧化物酶体增殖物激活受体γ(PPARγ)蛋白表达;并测空腹血糖、空腹胰岛素(FINS),计算胰岛素抵抗指数(HOMA-IR)。剩余大鼠继续喂养至12周,模型组和治疗组同时分别给予生理盐水(10 m1·kg~(-1)·d~(-1))和罗格列酮(3 mg·kg~(-1)·d~(-1))灌胃治疗。6周后,各组大鼠处死后按前述方法再次检测各指标。结果造模6周后,模型组大鼠空腹血糖、FINS、HOMA-IR升高(P＜0．05);主动脉病变评分明显增高(P＜0．01);光镜下可见典型的AS斑块;免疫组化染色显示PPARγ蛋白平均吸光度值明显增强(P＜0．01)。治疗6周后,治疗组与模型组比较,空腹血糖[(5．28±1．44)mmol/L和(8．90±2．60)mmol/L]、FISN[(31．04±24．20)mU/L和(48．38±27．62)mU/L]及HOMA-IR[(7．78±2．61)mmol/L和(12．42±4．13)mmol/L]水平降低(P＜0．05或P＜0．01),但与对照组[(6．01±0．89)mmol/L、(32．15±25．28)mU/L、7．79±2．58]比较,差异无统计学意义;治疗组主动脉斑块评分明显低于模型组(P＜0．01),但略高于对照组(P＜0．05)。光镜下可见治疗组AS病变较模型组明显减轻,且PPARγ蛋白平均吸光度值降低(P＜0．01)。结论罗格列酮治疗6周后,大鼠AS斑块明显消退,激活PPARγ和改善胰岛素抵抗可能是其作用机制之一。     

胰岛素抵抗大鼠视黄醇结合蛋白4骨骼肌磷脂酰肌醇3激酶的表达及吡格列酮的干预作用

目的 观察胰岛素抵抗(IR)大鼠体内视黄醇结合蛋白4(RBP4)、骨骼肌磷脂酰肌醇3激酶( P13K)和晚期氧化蛋白产物(AOPP)的水平,以及给予吡格列酮干预后其活性的变化,探讨RBP4与IR的关系及其可能的机制。 方法 将SPF级雄性Wistar大鼠35只随机分为2组,正常对照组（对照组）11只,饲以普通饲料;模型组24只,饲以高糖高脂饲料。模型组造模成功后再随机分为2个亚组,IR组和IR+吡格列酮干预组（干预组）,每组12只;IR组和干预组继续饲以高糖高脂饲料,干预组大鼠同时给予吡格列酮20mg·kg 1·d-1灌胃,持续8周。第16周末处死大鼠取血检测三酰甘油(TG)、高密度脂蛋白(HDL-C)、低密度脂蛋白(LDL-C)及空腹血糖(FBG)、空腹胰岛素(FINS),计算胰岛素抵抗指数(HOME-IR);酶联免疫吸附法(ELISA)检测血清RBP4水平,RT-PCR测定附睾脂肪组织RBP4表达;免疫组织化学染色检测骨骼肌PI3K水平;紫外分光光度计法测定AOPP水平;并取大鼠腹腔内肠系膜、附睾、腹膜反折处的脂肪组织称质量,计算腹部脂肪含量与体质量的比值。 结果 (1)IR组大鼠体质量16周后明显增加,TG、LDL-C、FINS以及脂体比较对照组均明显升高,而HDL-C则明显降低;吡格列酮干预后,干预组体质量、TG、LDL-C、FINS以及脂体比较IR组有明显下降,HDL-C明显升高;(2)IR组大鼠血清及附睾脂肪组织RBP4水平和血清AOPP水平明显高于对照组,干预组水平明显降低;(3)IR组大鼠骨骼肌组织PI3K表达水平明显低于对照组,吡格列酮干预其表达水平升高;(4)相关分析表明大鼠血清RBP4与FINS、脂体比、LDL-C呈正相关;与HDL-C、骨骼肌组织PI3K水平呈负相关。 结论 (1)IR大鼠RBP4、AOPP水平升高,RBP4是致IR的脂肪细胞因子,并可引起机体脂代谢紊乱及氧化应激增强;(2)RBP4降低大鼠胰岛素敏感性可能与其削弱胰岛素信号转导作用有关;(3)吡格列酮可降低IR大鼠RBP4及血清AOPP水平,增加骨骼肌PI3K表达,从而提高机体对胰岛素的敏感性。     

吡格列酮对高脂饮食诱导的胰岛素抵抗大鼠肝组织蛋白酪氨酸磷酸酶-1B及胰岛素受体底物-2表达的影响

目的 观察毗格列酮对高脂饮食诱导的IR大鼠肝组织蛋白酪氨酸磷酸酶-1B（PTP-1B）及胰岛素受体底物-2（IRS-2）表达的影响。方法40只SD大鼠随机分为高脂饮食（HF）组30只和正常对照（Nc）组10只,其中HF组又分为高脂对照（HFN）亚组和毗格列酮（HFP）亚组,每组各15只。喂养12周后,HFP亚组给予吡格列酮灌胃2周,并测定大鼠体重、FPG、Fins、TG、TC、IS。应用免疫组化、免疫印迹、免疫沉淀技术检测肝组织PTP-1B及IRS-2的表达。结果免疫组化：HFN亚组PTP-1B表达较NC组增高（P〈0．01）,HFP亚组较HFN亚组降低（P〈0．01）;免疫印迹：HFN、HFP亚组PTP-1B表达均高于NC组（P〈0．01或P〈0．05）,且HFP亚组低于HFN亚组（P〈0．01）;免疫沉淀：HFN亚组IRS-2磷酸化程度较NC组降低（P〈0．01）,HFP亚组较HFN亚组增高（P〈0．05）。结论吡格列酮能够改善IR,其作用机制可能与抑制PTP-1B表达,从而使胰岛素信号转导分子IRS-2表达增强有关。     

高脂饮食对老年大鼠肝脏脂肪酸代谢及胰岛素敏感性的影响

目的 探讨增龄和高脂饮食对大鼠肝脏脂肪酸代谢及胰岛素敏感性的影响,了解老年大鼠胰岛素抵抗(IR)的发病机制. 方法 将22～24月龄雄性Wistar大鼠随机分为老年对照组和高脂组;4～5月龄大鼠作为青年对照组.老年对照组和青年对照组给予基础饲料,高脂组给予高脂饲料,喂养8周.用高胰岛素-正葡萄糖钳夹实验评价各组大鼠胰岛素敏感性;肝脏三酰甘油经氯仿/甲醇抽提后用全自动生化分析仪测定. 结果 (1)老年对照组空腹血糖、胰岛素和游离脂肪酸均高于青年对照组,高脂组进一步升高,且血清三酰甘油和总胆同醇水平增高;(2)葡萄糖输注率老年对照组[(23.80±2.79)mU·kg-1·min-1]较青年对照组[(30.08±3.89)mU·kg-1·min-1]低,高脂组((18.83±2.18)mU·kg-1·min-1]最低,差异有统计学意义(P<0.01);高脂组8周末较4周末低;(3)肝脏三酰甘油老年对照组较青年对照组升高,分别为(16.6±4.8)μmol/g和(9.6±2.2)μmol/g,高脂组(24.7±6.6)μmol/g较老年对照组进一步升高(P<0.01);在老年组中,肝脏三酰甘油与葡萄糖输注率呈负相关.与空腹血糖呈正相关. 结论 与青年对照组比较,老年对照组更易出现脂肪酸代谢异常及IR;高脂饮食导致老年大鼠肝脏脂质积聚更加严重,进一步加重IR;肝脏脂质堆积可能参与了与增龄和高脂饮食相关IR的发生.     

罗格列酮上调高脂饮食老年大鼠骨骼肌GLUT4和PKB的表达

目的 观察高脂饮食对老年大鼠骨骼肌葡萄糖转运蛋白4(GLUT4)和蛋白激酶B(PKB)的表达变化及罗格列酮的干预效果.方法 老年大鼠随机分为对照组、高脂组(HF)、高脂+罗格列酮干预组(RSG),每组20只.应用清醒状态下正常葡萄糖高胰岛素钳夹技术的葡萄糖输注率评价胰岛素抵抗,用荧光定量PCR法和Western印迹技术检测骨骼肌GLUT4和PKB的表达.结果 高脂组骨骼肌长链脂酰辅酶A(LCACoA)升高而葡萄糖输注率明显下降(P＜0.01),骨骼肌GLUT4和PKB的表达明显降低(P＜0.05,P＜0.01),罗格列酮干预组显著缓解高脂组上述变化(P＜0.05,P＜0.01).结论 罗格列酮上调高脂饮食老年大鼠骨骼肌GLUT4和PKB的表达,是改善老年胰岛素抵抗的机制之一.     

罗格列酮增加apoE基因敲除小鼠主动脉粥样硬化斑块的稳定性研究

目的探讨罗格列酮对载脂蛋白E(apoE)基因敲除小鼠主动脉粥样硬化斑块稳定性的影响及其可能机制.方法32只6周龄apoE基因敲除小鼠随机分为罗格列酮组(18只)和对照组(14只),普通饮食14周后处死;切取小鼠主动脉根部制备石蜡切片,免疫组化法半定量测定两组粥样斑块内巨噬细胞、平滑肌细胞及炎性因子基质金属蛋白酶-9和肿瘤坏死因子-α的阳性率;Masson法半定量观察两组胶原纤维的灰度变化.结果罗格列酮组巨噬细胞的阳性率较对照组显著降低[分别为(16.1±2.5)%和(36.2±6.8)%,P＜0.05];平滑肌细胞的阳性率增加[分别为(38.5±7.2)%和(18.6±6.7)%,P＜0.05];胶原纤维的灰度显著降低[分别为(169.4±15.4)和(215.5±14.6),P＜0.05];基质金属蛋白酶-9分别为(16.0±4.8)%和(33.6±9.7)%,P＜0.05;肿瘤坏死因子-α的阳性率显著降低[分别为(15.9±2.9)%和(26.6±8.5)%,P＜0.05]. 结论罗格列酮可能通过下调局部炎性因子水平,改变斑块内的构成,稳定动脉粥样病变.     

高脂饮食大鼠脂肪组织甘油三酯脂酶的表达及罗格列酮的干预

目的 观察高脂饮食胰岛素抵抗大鼠脂肪组织中脂肪甘油三酯脂酶的表达及罗格列酮的干预效果.方法 5月龄雄性Wistar大鼠共40只随机分为正常对照组、高脂对照组和高脂+罗格列酮组,在清醒状态下行高胰岛素-正葡萄糖钳夹实验评价胰岛素敏感性,RT-PCR法和Western蛋白印迹技术检测脂肪组织中脂肪甘油三酯脂酶mRNA及蛋白表达.结果 (1)喂养4周末,高脂对照组的葡萄糖输注率低于正常对照组;8周末,高脂对照组甘油三酯、胆固醇、空腹血糖、空腹胰岛素、游离脂肪酸及内脏脂肪相对含量均明显升高,葡萄糖输注率降低;(2)罗格列酮干预后甘油三酯、胆固醇、血糖、胰岛素、游离脂肪酸和内脏脂肪相对含量降低,葡萄糖输注率升高;(3)与正常对照组相比,高脂对照组大鼠脂肪组织脂肪甘油三酯脂酶mRNA和蛋白的表达均减低,罗格列酮干预没有改变其表达;(4)ATGL蛋白的表达与胰岛素、游离脂肪酸负相关,与葡萄糖输注率呈正相关.结论 高脂喂养可引起胰岛素抵抗和脂肪组织脂肪甘油三酯脂酶的表达减低,这种变化在胰岛素抵抗早期可减少游离脂肪酸的释放.     

高脂饲养及罗格列酮干预对α细胞功能的影响

目的观察高脂饲养对SD大鼠α细胞形态和功能的影响及罗格列酮干预的作用。方法8周龄雄性SD大鼠36只随机分为3组:正常饲养组(CC,n=12)、高脂饲养组(CF,n=12)、高脂饲养 罗格列酮组(Ro,n=12,罗格列酮3mg·kg-1·d-1)。饲养28周时进行静脉糖耐量试验,于给糖后0、3、5、10min各留取动脉血待测胰岛素(Ins)及胰升糖素(Gg)水平,并同时测定即时血糖。采用组织对3H-2-脱氧葡萄糖(3H-2-DG)的吸收率评估胰岛素敏感性。免疫组织化学染色检测胰腺α细胞和β细胞的变化。结果CF组Gg在0、3、5、10min时水平[(119·3±12·4、82·3±6·4、72·2±5·8、68·2±9·1)ng/L]高于CC组[(96·8±9·1、67·6±5·9、57·9±5·3、55·3±6·9)ng/L,P<0·05];Ro组[(78·4±6·0、59·4±4·0、49·9±6·2、40·9±6·0)ng/L]显著低于CF组和CC组,P<0·01。各组Ins水平无统计学差异。α细胞积分下吸光度值,CF组及Ro组均高于CC组(1661±130及1532±132比1188±104,P<0·01及P<0·05);β细胞积分下吸光度值各组未见统计学差异。CF组的肌肉、肝脏和脂肪组织3H-2-DG吸收率明显低于CC组及Ro组(P值均<0·05)。结论高脂饲养SD大鼠引起胰岛素抵抗,同时伴有α细胞增生和Gg异常高分泌。罗格列酮可部分逆转这种变化。     

脂肪酸移位酶FAT/CD36与长链脂肪酸的结合机制

目的探讨脂肪酸移位酶FAT/CD36与长链脂肪酸的结合机制。方法 ELISA分析重组蛋白FAT/CD36与不同种类长链脂肪酸结合强弱机制,分子模拟对接进一步验证其结合机制并分析其可能作用位点。结果ELISA证明重组蛋白FAT/CD36与不同种类长链脂肪酸均显示特异性结合,结合值大小为油酸棕榈酸棕榈油酸肉豆蔻酸硬脂酸。分子模拟对接进一步验证FAT/CD36受体蛋白主要与其中的油酸、棕榈酸及棕榈油酸结合,且结合位点位于FAT/CD36受体蛋白胞外结构的Arg183-Lys-Gly-Lys-Arg-Asn-Leu-Ser-Tyr238区域组成的活性口袋。结论 FAT/CD36作为细胞长链脂肪酸转运的主要受体,其可能主要转运油酸、棕榈酸和棕榈油酸这三种脂肪酸。     

The combined mechanism of fatty acid translocase FAT/CD36 and long chain fatty acid

正Objective To investigate the binding mechanism of fatty acid translocase FAT/CD36 and long chain fatty acid.Methods ELISA was used to analyze the intensity mechanism of the purity of FAT/CD36 binding with different fatty acid,molecular simulation docking was used to further verify the binding mechanism and analyze its     

高脂饮食对老年大鼠骨骼肌脂肪酸含量及乙酰辅酶A羧化酶表达和活性的影响

目的 探讨增龄和高脂饮食对大鼠骨骼肌脂肪酸含量及乙酰辅酶A羧化酶(acetyl-coenzyme A carboxylase,ACC)表达和活性的影响.方法 将22～24月龄雄性Wistar大鼠随机分为老年对照组和高脂组;4～5月龄大鼠作为青年对照组.老年对照组和青年对照组给基础饲料,高脂组给予高脂饲料,喂养8周.用高胰岛素-正葡萄糖钳夹实验评价各组大鼠胰岛素敏感性,用全自动生化分析仪测定骨骼肌三酰甘油,用荧光分光光度计测定骨骼肌总的长链脂酰辅酶A含量,用Western-blot方法测定骨骼肌ACC、和磷酸化ACC(P-ACC)蛋白表达.结果 (1)老年对照组空腹血糖、胰岛索和游离脂肪酸高于青年对照组,高脂组上述几项指标进一步升高,并且出现血清三酰甘油和总胆固醇水平增高;(2)老年对照组葡萄糖输注率(glucose infusion rates,GIR)低于青年对照组,高脂组GIR低于老年对照组,高脂组GIR在8周末低于4周末;(3)老年对照组骨骼肌三酰甘油及长链脂酰辅酶A含量高于青年对照组,高脂组与老年对照组比较进一步升高;(4)老年对照组与青年对照组之间、高脂组与老年对照组之间骨骼肌ACC蛋白表达均无明显变化(P>0.05);骨骼肌P-ACC蛋白水平在老年对照组低于青年对照组,高脂组与老年对照组比较进一步降低(P<0.05或P<0.01).结论 与青年大鼠比较,老年大鼠更易出现脂肪酸代谢异常及胰岛素抵抗;高脂饮食导致老年大鼠骨骼肌脂质积聚更加严重,ACC活性的改变可能在骨骼肌脂质堆积和胰岛素抵抗发生中起了一定作用.     

Intramyocellular lipid accumulation is associated with permanent relocation ex vivo and in vitro of fatty acid translocase (FAT)/CD36 in obese patients

Aims/hypothesis

Intramyocellular lipids (IMCL) accumulation is a classical feature of metabolic diseases. We hypothesised that IMCL accumulate mainly as a consequence of increased adiposity and independently of type 2 diabetes. To test this, we examined IMCL accumulation in two different models and four different populations of participants: muscle biopsies and primary human muscle cells derived from non-obese and obese participants with or without type 2 diabetes. The mechanism regulating IMCL accumulation was also studied.

Methods

Muscle biopsies were obtained from ten non-obese and seven obese participants without type 2 diabetes, and from eight non-obese and eight obese type 2 diabetic patients. Mitochondrial respiration, citrate synthase activity and both AMP-activated protein kinase and acetyl-CoA carboxylase phosphorylation were measured in muscle tissue. Lipid accumulation in muscle and primary myotubes was estimated by Oil Red O staining and fatty acid translocase (FAT)/CD36 localisation by immunofluorescence.

Results

Obesity and type 2 diabetes are independently characterised by skeletal muscle IMCL accumulation and permanent FAT/CD36 relocation. Mitochondrial function is not reduced in type 2 diabetes. IMCL accumulation was independent of type 2 diabetes in cultured myotubes and was correlated with obesity markers of the donor. In obese participants, membrane relocation of FAT/CD36 is a determinant of IMCL accumulation.

Conclusions/interpretation

In skeletal muscle, mitochondrial function is normal in type 2 diabetes, while IMCL accumulation is dependent upon obesity or type 2 diabetes and is related to sarcolemmal FAT/CD36 relocation. In cultured myotubes, IMCL content and FAT/CD36 relocation are independent of type 2 diabetes, suggesting that distinct factors in obesity and type 2 diabetes contribute to permanent FAT/CD36 relocation ex vivo.     

Expression of the CD36 homolog (FAT) in fibroblast cells: effects on fatty acid transport.

An adipocyte membrane glycoprotein, (FAT), homologous to human CD36, has been previously implicated in the binding/transport of long-chain fatty acids. It bound reactive derivatives of long-chain fatty acids and binding was specific and associated with significant inhibition of fatty acid uptake. Tissue distribution of the protein and regulation of its expression were also consistent with its postulated role. In this report, we have examined the effects of FAT expression on rates and properties of fatty acid uptake by Ob17PY fibroblasts lacking the protein. Three clones (P21, P22, and P25) were selected based on FAT mRNA and protein levels. Cell surface labeling could be demonstrated with the anti-CD36 antibody FITC-OKM5. In line with this, the major fraction of immunoreactive FAT was associated with the plasma membrane fraction. Assays of oleate and/or palmitate uptake demonstrated higher rates in the three FAT-expressing clones, compared to cells transfected with the empty vector. Clone P21, which had the highest protein levels on Western blots, exhibited the largest increase in transport rates. Fatty acid uptake in FAT-expressing P21 cells reflected two components, a phloretin-sensitive high-affinity saturable component with a Km of 0.004 microM and a basal phloretin-insensitive component that was a linear function of unbound fatty acid. P21 cells incorporated more exogenous fatty acid into phospholipids, indicating that binding of fatty acids was followed by their transfer into the cell and that both processes were increased by FAT expression. The data support the interpretation that FAT/CD36 functions as a high-affinity membrane receptor/transporter for long-chain fatty acids.     

Apoptosis is associated with CD36/fatty acid translocase upregulation in non‐alcoholic steatohepatitis

Background & aims: Hepatocyte apoptosis is a key event in non‐alcoholic steatohepatitis (NASH). We studied the effect of obesity on free fatty acid (FFA) levels, fatty acid transport proteins (FATPs) and on extrinsic and intrinsic activation of apoptosis in the liver. Methods: Liver biopsies were harvested from 52 morbidly obese patients [body mass index (BMI): 53.82±1.41; age: 45±10.50; 15 males/37 females] undergoing bariatric surgery, and were scored for NASH, evaluated for fibrosis, and investigated for intrahepatic expression of FATPs, death receptors and cytosolic apoptosis‐related molecules. Findings were correlated with serum FFA levels and the degrees of intrahepatic (terminal dUTP nick end labelling) and systemic (M30) apoptosis. Results: In patients' liver sections, FATPs as well as select parameters of extrinsic and intrinsic apoptosis were found to be upregulated (CD36/FAT: × 11.56; FATP‐5: × 1.33; CD95/Fas: × 3.18; NOXA: × 2.79). These findings correlated with significantly elevated serum FFAs (control: 14.72±2.32 mg/dl vs. patients: 23.03±1.24 mg/dl) and M30 levels (control: 83.12±7.46 U/L vs. patients: 212.61±22.16 U/L). We found correlations between FATPs and apoptosis mediators as well as with histological criteria of NASH and fibrosis. Conclusions: Increased FFA and FATPs are associated with extrinsically and intrinsically induced apoptosis, liver damage and fibrosis in obese patients. Thus, FATPs may offer an interesting new approach to understand and potentially intervene NASH pathogenesis.