Krähenbühl S, Talos C, Reichen J
Department of Medicine, University of Berne, Switzerland.
Hepatology. 1994 May;19(5):1272-81. doi: 10.1002/hep.1840190528.
Hepatic metabolism of fatty acids is impaired in experimental animals with long-term bile duct ligation. To characterize the underlying defects, fatty acid metabolism was investigated in isolated hepatocytes and isolated liver mitochondria from rats subjected to long-term bile duct ligation or sham surgery. After starvation for 24 hr, the plasma beta-hydroxybutyrate concentration was decreased in rats with bile duct ligation as compared with control rats. Production of beta-hydroxybutyrate from butyrate, octanoate and palmitate by hepatocytes isolated from rats subjected to bile duct ligation was also decreased. Liver mitochondria from rats subjected to bile duct ligation showed decreased state 3 oxidation rates for L-glutamate, succinate, duroquinone, and fatty acids but not for ascorbate as substrate. State 3u oxidation rates (uncoupling with dinitrophenol) and activities of mitochondrial oxidases were also decreased in mitochondria from rats subjected to bile duct ligation. Direct assessment of the activities of the subunits of the electron transport chain revealed reduced activities of complex I, complex II and complex III in mitochondria from rats subjected to bile duct ligation. Activities of the beta-oxidation enzymes specific for short-chain fatty acids were all reduced in rats subjected to bile duct ligation. Mitochondrial protein content per hepatocyte was increased by 32% in rats subjected to bile duct ligation compared with control rats. Thus the studies directly demonstrate mitochondrial defects in fatty acid oxidation in rats subjected to bile duct ligation, which explain decreased ketosis during starvation.
在长期胆管结扎的实验动物中，脂肪酸的肝脏代谢受损。为了明确潜在缺陷，对接受长期胆管结扎或假手术的大鼠的分离肝细胞和分离肝线粒体中的脂肪酸代谢进行了研究。饥饿24小时后，胆管结扎大鼠的血浆β-羟基丁酸酯浓度与对照大鼠相比降低。从胆管结扎大鼠分离的肝细胞由丁酸、辛酸和棕榈酸生成β-羟基丁酸酯的量也减少。胆管结扎大鼠的肝线粒体以L-谷氨酸、琥珀酸、杜醌和脂肪酸作为底物时，其状态3氧化速率降低，但以抗坏血酸作为底物时未降低。胆管结扎大鼠的线粒体中状态3u氧化速率（用二硝基苯酚解偶联）和线粒体氧化酶活性也降低。对电子传递链亚基活性的直接评估显示，胆管结扎大鼠的线粒体中复合物I、复合物II和复合物III的活性降低。胆管结扎大鼠中短链脂肪酸特异性的β-氧化酶活性均降低。与对照大鼠相比，胆管结扎大鼠每个肝细胞的线粒体蛋白含量增加了32%。因此，这些研究直接证明了胆管结扎大鼠脂肪酸氧化中的线粒体缺陷，这解释了饥饿期间酮症减少的原因。
