Tsoko M, Beauseigneur F, Gresti J, Niot I, Demarquoy J, Boichot J, Bezard J, Rochette L, Clouet P
Laboratoire de Nutrition Cellulaire et Métabolique, EA DRED 564, Faculté des Sciences, Dijon, France.
Biochem Pharmacol. 1995 May 17;49(10):1403-10. doi: 10.1016/0006-2952(95)00019-v.
This study was designed to examine whether the depletion of L-carnitine may induce compensatory mechanisms allowing higher fatty acid oxidative activities in liver, particularly with regard to mitochondrial carnitine palmitoyltransferase I activity and peroxisomal fatty acid oxidation. Wistar rats received D-carnitine for 2 days and 3-(2,2,2,-trimethylhydrazinium)propionate (mildronate), a noncompetitive inhibitor of gamma-butyrobetaine hydroxylase, for 10 days. They were starved for 20 hr before being sacrificed. A dramatic reduction in carnitine concentration was observed in heart, skeletal muscles and kidneys, and to a lesser extent, in liver. Triacylglycerol content was found to be significantly more elevated on a gram liver and whole liver basis as well as per mL of blood (but to a lesser extent), while similar concentrations of ketone bodies were found in the blood of D-carnitine/mildronate-treated and control rats. In liver mitochondria, the specific activities of acyl-CoA synthetase and carnitine palmitoyltransferase I were enhanced by the treatment, while peroxisomal fatty acid oxidation was higher per gram of tissue. It is suggested that there may be an enhancement of cellular acyl-CoA concentration, a signal leading to increased liver fatty acid oxidation in acute carnitine deficiency.
本研究旨在探讨左旋肉碱的耗竭是否会诱导代偿机制，使肝脏中脂肪酸氧化活性更高，特别是在线粒体肉碱棕榈酰转移酶I活性和过氧化物酶体脂肪酸氧化方面。Wistar大鼠接受D-肉碱处理2天，并接受γ-丁甜菜碱羟化酶的非竞争性抑制剂3-(2,2,2-三甲基肼基)丙酸酯（米多君）处理10天。在处死前，它们禁食20小时。在心脏、骨骼肌和肾脏中观察到肉碱浓度显著降低，在肝脏中降低程度较小。发现每克肝脏、全肝以及每毫升血液中的三酰甘油含量显著升高（但程度较小），而在D-肉碱/米多君处理的大鼠和对照大鼠的血液中发现酮体浓度相似。在肝线粒体中，处理后酰基辅酶A合成酶和肉碱棕榈酰转移酶I的比活性增强，而过氧化物酶体脂肪酸氧化每克组织更高。提示在急性肉碱缺乏时，细胞酰基辅酶A浓度可能升高，这是导致肝脏脂肪酸氧化增加的信号。
