Defective hepatic mitochondrial respiratory chain in patients with nonalcoholic steatohepatitis
Defective hepatic mitochondrial respiratory chain in patients with nonalcoholic steatohepatitis
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DOI：
10.1002/hep.1840380426
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发表时间：
2003-10
期刊：
影响因子：
13.5
通讯作者：
M. Pérez-Carreras;P. del Hoyo;Miguel Ángel Martín;J. Rubio;Ana Martín;G. Castellano;F. Colina;
中科院分区：
文献类型：
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作者：
M. Pérez-Carreras;P. del Hoyo;Miguel Ángel Martín;J. Rubio;Ana Martín;G. Castellano;F. Colina;
线粒体功能障碍可能在非酒精性脂肪性肝炎（NASH）的发病机制中起重要作用。本研究的目的是评估NASH中游离脂肪酸（FFA）转运到线粒体或线粒体呼吸链（MRC）复合物的活性是否受损。在NASH患者和对照受试者中，我们测量了肝组织中游离肉毒碱、短链酰基肉毒碱（SCAC）和长链酰基肉毒碱（LCAC）酯、肉毒碱棕榈酰转移酶（CPT）活性和MRC酶活性以及肿瘤坏死因子α（TNF-α）血清浓度、胰岛素抵抗稳态代谢评估（HOMAIR）和体重指数（BMI）。在NASH患者中，LCAC/游离肉毒碱比率显著增加，SCAC/游离肉毒碱比率降低。在NASH患者中，MRC复合物的活性降低至相应对照值的63% ± 20%（复合物I）、58.5% ± 16.7%（复合物II）、70.6% ± 10.3%（复合物III）、62.5% ± 13%（复合物IV）和42.4% ± 9.1%（腺苷三磷酸合酶）。这些复合物的活性与血清TNF-α和HOMAIR显著相关。NASH患者的血清TNF-α（36.3 ± 23.1 pg/mL）、HOMAIR（4.5 ± 2.38）和BMI（29.9 ± 3.5 kg/m2）值显著升高。总之，MRC复合物的活性在NASH患者的肝组织中降低。这种功能障碍与血清TNF-α、胰岛素抵抗和BMI值相关。（Hepatology 2003;38：999-1007）。
Mitochondrial dysfunction might play a central role in the pathogenesis of nonalcoholic steatohepatits (NASH). The aims of this study were to evaluate whether free fatty acid (FFA) transport into the mitochondria or the activity of mitochondria respiratory chain (MRC) complexes are impaired in NASH. In patients with NASH and control subjects, we measured free carnitine, short‐chain acylcarnitine (SCAC) and long‐chain acylcarnitine (LCAC) esters, carnitine palmitoyltransferase (CPT) activity, and MRC enzyme activity in liver tissue as well as serum concentration of tumor necrosis factor α (TNF‐α), homeostatic metabolic assessment of insulin resistance (HOMAIR), and body mass index (BMI). In patients with NASH, the LCAC/free carnitine ratio was significantly increased and the SCAC/free carnitine ratio was decreased. In patients with NASH, the activity of the MRC complexes was decreased to 63% ± 20% (complex I), 58.5% ± 16.7% (complex II), 70.6% ± 10.3% (complex III), 62.5% ± 13% (complex IV), and 42.4% ± 9.1% (adenosine triphosphate synthase) of the corresponding control values. Activity of these complexes correlated significantly with serum TNF‐α and HOMAIR. Serum TNF‐α (36.3 ± 23.1 pg/mL), HOMAIR (4.5 ± 2.38), and BMI (29.9 ± 3.5 kg/m2) values were significantly increased in patients with NASH. In conclusion, activities of MRC complexes were decreased in liver tissue of patients with NASH. This dysfunction correlated with serum TNF‐α, insulin resistance, and BMI values. (Hepatology 2003;38:999–1007).