Biochemical study on lipid metabolism in lipid storage myopathy

我们研究了脂质储存性肌病患者培养成纤维细胞的脂质代谢。患者有缓慢进行性肌病，视网膜色素变性，神经感觉性听力丧失。骨骼肌纤维、白细胞和培养成纤维细胞中有许多含有中性脂质的空泡。骨骼肌中肉毒碱含量、肉毒碱棕榈酰基转移酶和线粒体电子传递系统活性正常，酰基肉毒碱与游离肉毒碱比值升高。培养成纤维细胞的甘油三酯含量水平比对照组高10倍，脂肪酸组成正常。培养成纤维细胞长链脂肪酸氧化反应受损（为对照组的37%），而中链和短链脂肪酸氧化反应正常。长链脂肪酸氧化酶活性正常。当用放射性标记油酸喂养成纤维细胞6小时后，甘油三酯的合成比对照组增加了两倍。脉冲追踪实验表明，合成的甘油三酯降解减少。成纤维细胞提取物的酸性、中性和碱性脂肪酶活性均处于正常水平。长链脂肪酸氧化和甘油三酯降解的调控均可能受损，从而导致细胞内蓄积。

We studied lipid metabolism in clutured fibroblasts from a patient with lipid storage myopathy. The patient has slowly progressive myopathy, pigmentary retinal degeneration, neurosensory hearing loss. There were many vacuoles containing neutral lipid in skeletal muscle fibers, leukocytes, and cultured fibroblasts.Carnitine content and the activities of carnitine palmitoyltransferase and mitochondrial electron transport system were normal, and the ratio of acylcarnitine to free carnitine was elevated in skeletal muscle. The level of triglyceride content of the cultured fibroblasts was ten times higher than that of controls, and fatty acid composition was normal. The oxidation of long-chain fatty acid was impaired (37% of control values), while the oxidation reaction of medium-chain and short-chain fatty acid were normal in the cultured fibroblasts. The activities of enzymes working on long-chain fatty acid oxidation were normal. When the fibroblasts were fed with radiolabeled oleate for 6 hrs, the triglyceride synthsis was increased twice as controls. Pulse-chase experiment showed the reduced degradation of synthesized triglyceride. The activities of acidic, neutral, and alkaline lipase were normal level in fibroblasts extracts.The regulation in both long-chain fatty acid oxidation and triglyceride degradation may be impaired, which causes the intracellure accumulation.