Roles of Diacylglycerols and Ceramides in Hepatic Insulin Resistance.
Roles of Diacylglycerols and Ceramides in Hepatic Insulin Resistance.
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DOI：
10.1016/j.tips.2017.04.004
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发表时间：
2017-07
影响因子：
13.8
通讯作者：
Shulman GI
中科院分区：
文献类型：
--
作者：
Petersen MC;Shulman GI
尽管大量证据表明肝脏脂质积累与肝脏胰岛素抵抗有关，但这种关联的机制基础尚不完全清楚，且存在争议。二酰基甘油和神经酰胺被认为是脂质诱导的肝脏胰岛素抵抗的两种被研究得最好的介质。这两种脂质首先与骨骼肌的胰岛素抵抗有关，随后假设介导肝脏的胰岛素抵抗。然而，二酰基甘油和神经酰胺在肝脏胰岛素抵抗中的假定作用已被证明比最初想象的要复杂，各种遗传和药理学操作产生了大量偶尔相互矛盾的数据。在这篇综述中，我们研究了这一领域的现状，将批判的目光转向二酰基甘油和神经酰胺作为脂质诱导的肝脏胰岛素抵抗的介质。
Although ample evidence links hepatic lipid accumulation with hepatic insulin resistance, the mechanistic basis of this association is incompletely understood and controversial. Diacylglycerols and ceramides have emerged as the two best-studied putative mediators of lipid-induced hepatic insulin resistance. Both lipids were first associated with insulin resistance in skeletal muscle, and subsequently hypothesized to mediate insulin resistance in liver. However, the putative roles for diacylglycerols and ceramides in hepatic insulin resistance have proved more complex than originally imagined, with various genetic and pharmacologic manipulations yielding a vast and occasionally contradictory trove of data to sort through. In this review, we examine the state of this field, turning a critical eye toward both diacylglycerols and ceramides as putative mediators of lipid-induced hepatic insulin resistance.