Exercise alters liver mitochondria phospholipidomic profile and mitochondrial activity in non-alcoholic steatohepatitis
Exercise alters liver mitochondria phospholipidomic profile and mitochondrial activity in non-alcoholic steatohepatitis
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DOI：
10.1016/j.biocel.2014.07.011
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发表时间：
2014-09-01
影响因子：
4
通讯作者：
Magalhaes, Jose
中科院分区：
文献类型：
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作者：
Goncalves, Ines O.;Maciel, Elisabete;Magalhaes, Jose
线粒体膜脂质组成是非酒精性脂肪性肝炎（NASH）的关键因素。运动是针对NASH最常用的治疗策略，也是一种潜在的脂质膜调节剂。因此，我们旨在分析体育锻炼是否对NASH诱导的线粒体膜变化产生预防（自愿体育活动- VPA）和治疗（耐力训练- ET）作用。SD大鼠36只，随机分为正常饮食组（SS组，n = 12）、VPA组（SVPA组，n = 6）、高脂饮食组（HS组，n = 12）和VPA组（HVPA组，n = 6）。经过9周的饮食特定喂养后，SS和HS组的一半参与了8周/5天/周/1小时/天的ET计划（SET，HET）。分离肝线粒体用于氧消耗和跨膜电位（Delta Psi）测定。线粒体磷脂类和脂肪酸分别通过薄层色谱法和气相色谱法进行定量，而心磷脂（CL），磷脂酰胆碱（PC），磷脂酰乙醇胺（PE）和磷脂酰肌醇（PI）的分子概况通过电喷雾质谱法测定。与NASH的组织学体征平行，高脂饮食降低PI、CL和PC/PE比值，而久坐动物中PE和磷脂酸含量增加（HS vs SS）。此外，亚油酸，单不饱和脂肪酸含量减少，饱和脂肪酸（SFAS）增加。沿着磷脂组学改变，HS动物显示呼吸控制率（RCR）、Delta Psi和FCCP诱导的解偶联呼吸降低。(HS相对于SS）。磷脂质组（PC/PE，SFAS）和线粒体呼吸的变化抵消运动干预。在NASH模型中，运动作为预防（VPA）或治疗（ET）策略保留了肝脏线粒体磷脂质组学特征并维持了线粒体功能。(C)2014爱思唯尔有限公司版权所有。
Mitochondrial membrane lipid composition is a critical factor in non-alcoholic steatohepatitis (NASH). Exercise is the most prescribed therapeutic strategy against NASH and a potential modulator of lipid membrane. Thus, we aimed to analyze whether physical exercise exerted preventive (voluntary physical activity - VPA) and therapeutic (endurance training - ET) effect on NASH-induced mitochondrial membrane changes. Sprague-Dawley rats (n = 36) were divided into standard-diet sedentary (SS, n = 12), standard-diet VPA (SVPA, n = 6), high-fat diet sedentary (HS, n = 12) and high-fat diet VPA (HVPA, n = 6). After 9 weeks of diet-specific feeding, half of SS and HS group were engaged in an ET program for 8 weeks/5 day/week/1 h/day (SET, HET). Liver mitochondria were isolated for oxygen consumption and transmembrane-electric potential (Delta Psi) assays. Mitochondrial phospholipid classes and fatty acids were quantified through thin layer chromatography and gas chromatography, respectively, while cardiolipin (CL), phosphatidylcholine (PC) phosphatidylethanolamine (PE) and phosphatidylinositol (PI) molecular profile was determined by electrospray mass spectrometry. In parallel with histological signs of NASH, high-fat diet decreased PI, CL and PC/PE ratio, whereas PE and phosphatidic acid content increased in sedentary animals (HS vs. SS). Moreover, a decrease in linolelaidic, monounsaturated fatty acids content and an increase in saturated fatty acids (SFAS) were observed. Along with phospholipidomic alterations, HS animals showed a decrease in respiratory control ratio (RCR), Delta Psi and FCCP-induced uncoupling respiration.(HS vs. SS). Both phospholipidomic (PC/PE, SFAS) and mitochondrial respiratory alterations were counteracted by exercise interventions. Exercise used as preventive (VPA) or therapeutic (ET) strategies preserved liver mitochondrial phospholipidomic profile and maintained mitochondrial function in a model of NASH. (C) 2014 Elsevier Ltd. All rights reserved.