Henninger C, Clouet P, Cao Danh H, Pascal M, Bezard J
Laboratoire de Physiologie Animale et de la Nutrition, U.A. CNRS 273, Faculté des Sciences Mirande, Dijon, France.
Biochem Pharmacol. 1987 Oct 1;36(19):3231-6. doi: 10.1016/0006-2952(87)90638-1.
Obese Zucker rats were dosed orally for one week with fenofibrate (100 mg/kg). Liver weights of treated rats as expressed as percent of body weight were slightly increased, while protein, DNA and lipid contents were unaffected per g of liver or increased when expressed in whole liver. Compared with the control animals, activities of fatty acid oxidase, of the peroxisomal fatty acid-oxidizing system and of catalase were markedly increased by fenofibrate both per g of liver and per total liver, while urate oxidase activity was unchanged when expressed per g of liver. The activity of monoamine oxidase and that of cytochrome c oxidase used as marker enzymes for mitochondria were increased only when expressed per total liver. However, fenofibrate treatment induced a pronounced increase in the activities of mitochondrial palmitoyl-CoA dehydrogenase and carnitine acyltransferases, particularly carnitine acetyltransferase. Fenofibrate also caused a significant increase of carnitine content in liver and hepatic mitochondria. The greatest observed increases were in free carnitine and in the rate of carnitine-dependent oleate oxidation, which might be favoured in vivo by a lesser sensitivity of CPT-I to a malonyl-CoA inhibitory effect. The present results suggest that fenofibrate treatment induces increased hepatic mitochondrial beta-oxidation in obese Zucker rats.
给肥胖的Zucker大鼠口服非诺贝特（100毫克/千克），持续一周。经处理的大鼠肝脏重量以占体重的百分比表示略有增加，而每克肝脏的蛋白质、DNA和脂质含量未受影响，以全肝表示时则有所增加。与对照动物相比，非诺贝特使每克肝脏和整个肝脏的脂肪酸氧化酶、过氧化物酶体脂肪酸氧化系统和过氧化氢酶的活性显著增加，而每克肝脏的尿酸氧化酶活性未改变。用作线粒体标记酶的单胺氧化酶和细胞色素c氧化酶的活性仅在以整个肝脏表示时增加。然而，非诺贝特处理导致线粒体棕榈酰辅酶A脱氢酶和肉碱酰基转移酶，特别是肉碱乙酰转移酶的活性显著增加。非诺贝特还使肝脏和肝线粒体中的肉碱含量显著增加。观察到的最大增加是游离肉碱和肉碱依赖性油酸氧化速率的增加，这可能是由于体内肉碱棕榈酰转移酶I对丙二酰辅酶A抑制作用的敏感性较低所致。目前的结果表明，非诺贝特处理可诱导肥胖Zucker大鼠肝脏线粒体β氧化增加。
