Department of Human Health and Nutritional Science, University of Guelph, Guelph, ON, Canada N1G 2W1.
Diabetologia. 2012 Feb;55(2):479-88. doi: 10.1007/s00125-011-2367-2. Epub 2011 Nov 19.
AIMS/HYPOTHESIS: Little is known about the subcellular distribution of lipids in insulin-resistant skeletal muscle. However, it has recently been suggested that lipid accumulation in the subsarcolemmal region directly contributes to insulin resistance. Therefore we hypothesised that regional differences in lipid distribution in insulin-resistant muscle may be mediated by: (1) a reduction in fatty acid trafficking into mitochondria; and/or (2) a regional increase in the enzymes regulating lipid synthesis.
Transmission electron microscopy was used to quantify lipid droplet and mitochondrial abundance in the subsarcolemmal and intermyofibrillar compartments in red and white muscles from lean and obese Zucker rats. To estimate rates of lipid trafficking into mitochondria, the metabolic fate of radiolabelled palmitate was determined. Key enzymes of triacylglycerol synthesis were also determined in each subcellular region.
Subsarcolemmal-compartmentalised lipids represented a small absolute fraction of the overall lipid content in muscle, as regardless of fibre composition (red/white) or phenotype (lean/obese), lipid droplets were more prevalent in the intermyofibrillar region, whereas insulin-resistant white muscles were devoid of subsarcolemmal-compartmentalised lipid droplets. While, in obese animals, lipid droplets accumulated in both subcellular regions, in red muscle of these animals lipids only appeared to be trafficked away from intermyofibrillar mitochondria, a process that cannot be explained by regional differences in the abundance of triacylglycerol esterification enzymes.
CONCLUSIONS/INTERPRETATION: Lipid accumulation in the subsarcolemmal region is not necessary for insulin resistance. In the intermyofibrillar compartment, the diversion of lipids away from mitochondria in insulin-resistant animals probably contributes to lipid accumulation in this subcellular area.
目的/假设：关于胰岛素抵抗骨骼肌中脂质的亚细胞分布知之甚少。然而，最近有人提出，肌小节下区域的脂质堆积直接导致胰岛素抵抗。因此，我们假设胰岛素抵抗肌肉中脂质分布的区域差异可能是由以下因素介导的：（1）脂肪酸向线粒体的转运减少；和/或（2）调节脂质合成的酶在局部增加。
使用透射电子显微镜来定量红肌和白肌中肌小节下和肌纤维间区的脂滴和线粒体的丰度。为了估计脂质向线粒体的转运速率，测定了放射性标记的软脂酸的代谢命运。还在每个亚细胞区域测定了三酰甘油合成的关键酶。
无论纤维组成（红/白）或表型（瘦/胖）如何，肌小节下区的脂质代表肌肉中总脂质含量的一小部分，脂滴在肌纤维间区更为普遍，而胰岛素抵抗的白肌则缺乏肌小节下区的脂滴。虽然在肥胖动物中，脂质滴在两个亚细胞区都积累，但在这些动物的红肌中，脂质似乎只是从肌纤维间的线粒体中转运出去，这一过程不能用三酰甘油酯化酶丰度的区域差异来解释。
结论/解释：肌小节下区域的脂质积累不是胰岛素抵抗所必需的。在肌纤维间区，胰岛素抵抗动物中线粒体的脂质分流可能导致该亚细胞区脂质的积累。
