Biochemical study on lipid metabolism in lipid storage myopathy

我们研究了来自一位脂质沉积性肌病患者的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内有大量含有中性脂质的空泡，肉碱含量、肉碱棕榈酰基转移酶和线粒体电子传递系统活性正常，骨骼肌酰基肉碱/游离肉碱比值升高。培养的成纤维细胞甘油三酯含量为对照组的10倍，脂肪酸组成正常。培养的成纤维细胞长链脂肪酸氧化受损(为对照的37%)，而中链和短链脂肪酸氧化反应正常。作用于长链脂肪酸氧化的酶活性正常。当用放射性标记油酸盐喂养成纤维细胞6h时，甘油三酯合成量是对照组的两倍。脉冲追逐实验表明，合成的甘油三酯降解率降低。成纤维细胞提取液中酸性、中性和碱性脂肪酶活性正常，对长链脂肪酸氧化和甘油三酯降解的调节可能受损，导致细胞内堆积。

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.