Centre for Physical Activity and Nutrition (C-PAN) Research, School of Exercise and Nutrition Sciences, Deakin University, Burwood, 3125 VIC, Australia.
Department of Physiology, Monash University, Clayton, 3800 VIC, Australia.
Cell Metab. 2015 May 5;21(5):718-30. doi: 10.1016/j.cmet.2015.04.001.
Accumulation of diacylglycerol (DG) in muscle is thought to cause insulin resistance. DG is a precursor for phospholipids, thus phospholipid synthesis could be involved in regulating muscle DG. Little is known about the interaction between phospholipid and DG in muscle; therefore, we examined whether disrupting muscle phospholipid synthesis, specifically phosphatidylethanolamine (PtdEtn), would influence muscle DG content and insulin sensitivity. Muscle PtdEtn synthesis was disrupted by deleting CTP:phosphoethanolamine cytidylyltransferase (ECT), the rate-limiting enzyme in the CDP-ethanolamine pathway, a major route for PtdEtn production. While PtdEtn was reduced in muscle-specific ECT knockout mice, intramyocellular and membrane-associated DG was markedly increased. Importantly, however, this was not associated with insulin resistance. Unexpectedly, mitochondrial biogenesis and muscle oxidative capacity were increased in muscle-specific ECT knockout mice and were accompanied by enhanced exercise performance. These findings highlight the importance of the CDP-ethanolamine pathway in regulating muscle DG content and challenge the DG-induced insulin resistance hypothesis.
二酰基甘油 (DG) 在肌肉中的积累被认为会导致胰岛素抵抗。DG 是磷脂的前体，因此磷脂合成可能参与调节肌肉 DG。关于肌肉中磷脂和 DG 之间的相互作用知之甚少；因此，我们研究了破坏肌肉磷脂合成，特别是磷脂酰乙醇胺 (PtdEtn) 是否会影响肌肉 DG 含量和胰岛素敏感性。通过删除 CTP:磷酸乙醇胺胞苷转移酶 (ECT) 来破坏肌肉 PtdEtn 合成，ECT 是 CDP-乙醇胺途径中的限速酶，也是 PtdEtn 产生的主要途径。虽然肌肉特异性 ECT 敲除小鼠中的 PtdEtn 减少，但细胞内和膜相关的 DG 明显增加。然而，重要的是，这与胰岛素抵抗无关。出乎意料的是，肌肉特异性 ECT 敲除小鼠中的线粒体生物发生和肌肉氧化能力增加，并且伴随着运动性能的提高。这些发现强调了 CDP-乙醇胺途径在调节肌肉 DG 含量中的重要性，并挑战了 DG 诱导的胰岛素抵抗假说。
