Remodeling glycerophospholipids affects obesity-related insulin signaling in skeletal muscle.
Remodeling glycerophospholipids affects obesity-related insulin signaling in skeletal muscle.
复制标题
重塑甘油磷脂会影响骨骼肌中与肥胖相关的胰岛素信号。
DOI：
10.1172/jci148176
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Wolfgang,MichaelJ
中科院分区：
文献类型：
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作者：
Wolfgang,MichaelJ
人们早就知道，脂肪酸可以对骨骼肌中的胰岛素信号产生不利或积极的影响，具体取决于链长度或饱和度，因此可能是全身胰岛素敏感性的主要驱动因素。然而，将脂肪酸与骨骼肌中胰岛素信号传导联系起来的详细机制一直难以捉摸。在本期 JCI 中，Ferrara 等人。提出了一种膜脂重塑介导骨骼肌胰岛素敏感性的模型。作者证明，溶血磷脂酰胆碱酰基转移酶 3 (LPCAT3) 在肥胖受试者的骨骼肌中诱导膜甘油磷脂脂肪酸重塑，从而抑制胰岛素信号传导和葡萄糖耐量。小鼠模型中 LPCAT3 功能的丧失或增强表明，Lpcat3 对于高脂肪饮食诱导的肌肉胰岛素抵抗来说既是必需的，也是充分的。这些结果表明，肌肉细胞膜的理化特性可能会驱动胰岛素敏感性，从而驱动全身葡萄糖不耐受。
It has long been known that fatty acids can either adversely or positively affect insulin signaling in skeletal muscle, depending on chain length or saturation, and can therefore be primary drivers of systemic insulin sensitivity. However, the detailed mechanisms linking fatty acids to insulin signaling in skeletal muscle have been elusive. In this issue of theJCI, Ferrara et al. suggest a model whereby membrane lipid remodeling mediates skeletal muscle insulin sensitivity. The authors demonstrate that membrane glycerophospholipid fatty acid remodeling by lysophosphatidylcholine acyltransferase 3 (LPCAT3) in skeletal muscle from subjects with obesity was induced, suppressing insulin signaling and glucose tolerance. Loss or gain of LPCAT3 function in mouse models showed thatLpcat3was both required and sufficient for high-fat diet–induced muscle insulin resistance. These results suggest that the physiochemical properties of muscle cell membranes may drive insulin sensitivity and, therefore, systemic glucose intolerance.