Department of Endocrinology, Huzhou Central Hospital, Zhejiang 313000, China.
J Diabetes Res. 2013;2013:163062. doi: 10.1155/2013/163062. Epub 2013 Nov 11.
By specific knockout of carnitine palmitoyl transferase 1b (CPT1b) in skeletal muscles, we explored the effect of CPT1b deficiency on lipids and insulin sensitivity.
Mice with specific knockout of CPT1b in skeletal muscles (CPT1b M-/-) were used for the experiment group, with littermate C57BL/6 as controls (CPT1b). General and metabolic profiles were measured and compared between groups. mRNA expression and CPT1 activity were measured in skeletal muscle tissues and compared between groups. Mitochondrial fatty acid oxidation (FAO), triglycerides (TAGs), diglycerides (DAGs), and ceramides were examined in skeletal muscles in two groups. Phosphorylated AKT (pAkt) and glucose transporter 4 (Glut4) were determined with real-time polymerase chain reaction (RT-PCR). Insulin tolerance test, glucose tolerance test, and pyruvate oxidation were performed in both groups.
CPT1b M-/- model was successfully established, with impaired muscle CPT1 activity. Compared with CPT1b mice, CPT1b M-/- mice had similar food intake but lower body weight or fat mass and higher lipids but similar glucose or insulin levels. Their mitochondrial FAO of skeletal muscles was impaired. There were lipids accumulations (TAGs, DAGs, and ceramides) in skeletal muscle. However, pAkt and Glut4, insulin sensitivity, glucose tolerance, and pyruvate oxidation were preserved.
Skeletal muscle-specific CPT1 deficiency elevates lipotoxic intermediates but preserves insulin sensitivity.
通过特异性敲除骨骼肌中的肉碱棕榈酰转移酶 1b（CPT1b），我们研究了 CPT1b 缺乏对脂质和胰岛素敏感性的影响。
实验采用骨骼肌中特异性敲除 CPT1b 的小鼠（CPT1b M-/-）作为实验组，以同窝 C57BL/6 小鼠作为对照组（CPT1b）。测量并比较两组的一般和代谢特征。测量骨骼肌组织中的 mRNA 表达和 CPT1 活性并进行比较。检查两组骨骼肌中的线粒体脂肪酸氧化（FAO）、甘油三酯（TAGs）、二甘油酯（DAGs）和神经酰胺。通过实时聚合酶链反应（RT-PCR）测定磷酸化 AKT（pAkt）和葡萄糖转运蛋白 4（Glut4）。在两组中进行胰岛素耐量试验、葡萄糖耐量试验和丙酮酸氧化。
成功建立了 CPT1b M-/-模型，肌肉 CPT1 活性受损。与 CPT1b 小鼠相比，CPT1b M-/-小鼠的食物摄入量相似，但体重或脂肪量较低，脂质较高，但葡萄糖或胰岛素水平相似。他们的骨骼肌线粒体 FAO 受损。骨骼肌中存在脂质堆积（TAGs、DAGs 和神经酰胺）。然而，pAkt 和 Glut4、胰岛素敏感性、葡萄糖耐量和丙酮酸氧化得到了保留。
骨骼肌特异性 CPT1 缺乏会增加脂毒性中间产物，但保留胰岛素敏感性。
