Department of Human Biology, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre+, 6200MD Maastricht, The Netherlands.
Prog Lipid Res. 2012 Jan;51(1):36-49. doi: 10.1016/j.plipres.2011.11.003. Epub 2011 Nov 19.
Ectopic fat accumulation has been linked to lipotoxic events, including the development of insulin resistance in skeletal muscle. Indeed, intramyocellular lipid storage is strongly associated with the development of type 2 diabetes. Research during the last two decades has provided evidence for a role of lipid intermediates like diacylglycerol and ceramide in the induction of lipid-induced insulin resistance. However, recently novel data has been gathered that suggest that the relation between lipid intermediates and insulin resistance is less straightforward than has been previously suggested, and that there are several routes towards lipid-induced insulin resistance. For example, research in this field has shifted towards imbalances in lipid metabolism and lipid droplet dynamics. Next to imbalances in key lipogenic and lipolytic proteins, lipid droplet coat proteins appear to be essential for proper intramyocellular lipid storage, turnover and protection against lipid-induced insulin resistance. Here, we discuss the current knowledge on lipid-induced insulin resistance in skeletal muscle with a focus on the evidence from human studies. Furthermore, we discuss the available data that provides supporting mechanistic information.
异位脂肪积累与脂毒性事件有关，包括骨骼肌胰岛素抵抗的发展。事实上，肌内脂质储存与 2 型糖尿病的发展密切相关。在过去二十年的研究中，有证据表明二酰基甘油和神经酰胺等脂质中间体在诱导脂质诱导的胰岛素抵抗中起作用。然而，最近收集到的新数据表明，脂质中间体与胰岛素抵抗之间的关系并不像以前所认为的那样简单，而且存在几种导致脂质诱导的胰岛素抵抗的途径。例如，该领域的研究已经转向脂质代谢和脂滴动力学的失衡。除了关键的生脂和脂解蛋白的失衡外，脂滴外衣蛋白似乎对于适当的肌内脂质储存、周转以及防止脂质诱导的胰岛素抵抗也是必不可少的。在这里，我们讨论了骨骼肌中脂质诱导的胰岛素抵抗的最新知识，重点是来自人体研究的证据。此外，我们还讨论了提供支持机制信息的现有数据。
