Locci Cubeddu T, Masiello P, Pollera M, Bergamini E
Biochim Biophys Acta. 1985 Mar 29;839(1):96-104. doi: 10.1016/0304-4165(85)90186-2.
The mechanisms involved in the inhibitory effects of antilipolytic agents on rat liver peroxisomal fatty acid oxidative activity have been explored. Treatment of fasting rats with antilipolytic drugs (either 3,5-dimethylpyrazole (12 mg/kg body weight) or Acipimox (25 mg/kg body weight] resulted in a decrease in free fatty acid and glucose plasma levels within 5-10 and in a significant increase in the plasma glucagon to insulin ratio within 15. Changes in the fatty acid oxidative activity appeared with a 2.5-3 h delay and were then very rapid (a 30-40% decrease in the activity occurred in additional 2 h). Many peroxisomal enzyme activities (including non-beta-oxidative activities such as uricase and D-amino acid oxidase) exhibited similar changes with the same delay. Simultaneously with the enzyme changes, at the electron microscope level many autophagic vacuoles were detected in the liver cells, often containing peroxisomal structures. Glutamine, an inhibitor of proteolysis in vivo, prevented the decrease in enzyme activities. It was concluded that the decrease in peroxisomal enzyme activities may be the consequence of enhanced peroxisome degradation due to the stimulation of autophagic processes in liver cells.
研究了抗脂解剂对大鼠肝脏过氧化物酶体脂肪酸氧化活性的抑制作用机制。用抗脂解药物（3,5 - 二甲基吡唑（12毫克/千克体重）或阿西莫司（25毫克/千克体重））处理禁食大鼠，5 - 10分钟内血浆游离脂肪酸和葡萄糖水平降低，15分钟内血浆胰高血糖素与胰岛素比值显著升高。脂肪酸氧化活性的变化延迟2.5 - 3小时出现，然后非常迅速（在另外2小时内活性下降30 - 40%）。许多过氧化物酶体酶活性（包括非β - 氧化活性，如尿酸酶和D - 氨基酸氧化酶）表现出相同延迟的类似变化。与酶变化同时，在电子显微镜水平，肝细胞中检测到许多自噬泡，常含有过氧化物酶体结构。谷氨酰胺是体内蛋白水解的抑制剂，可防止酶活性下降。得出结论，过氧化物酶体酶活性的降低可能是由于肝细胞自噬过程受刺激导致过氧化物酶体降解增强的结果。
