Department of Health and Physical Activity, University of Pittsburgh, Trees Hall Rm 134D, Allequippa Street and Darragh Street, Pittsburgh, PA 15260, USA.
Trends Endocrinol Metab. 2012 Aug;23(8):391-8. doi: 10.1016/j.tem.2012.05.009. Epub 2012 Jun 20.
Intramyocellular lipid (IMCL) is predominantly stored as intramuscular triglyceride (IMTG) in lipid droplets and is utilized as metabolic fuel during physical exercise. IMTG is also implicated in muscle insulin resistance (IR) in type 2 diabetes. However, it has become apparent that lipid moieties such as ceramide and diacylglycerol are the likely culprits of IR. This article reviews current knowledge of IMCL-mediated IR and important areas of investigation, including myocellular lipid transport and lipid droplet proteins. Several crucial questions remain unanswered, such as the identity of specific ceramide and diacylglycerol species that mediate IR in human muscle and their subcellular location. Quantitative lipidomics and proteomics of targeted subcellular organelles will help to better define the mechanisms underlying pathological IMCL accumulation and IR.
肌内甘油三酯(IMTG)是肌肉内脂质的主要储存形式,以脂滴的形式存在,在体力活动中被用作代谢燃料。IMTG 也与 2 型糖尿病中的肌肉胰岛素抵抗(IR)有关。然而,脂类如神经酰胺和二酰基甘油很可能是导致 IR 的罪魁祸首。本文综述了目前关于 IMCL 介导的 IR 以及包括肌细胞脂质转运和脂滴蛋白在内的重要研究领域的知识。目前仍有几个关键问题尚未得到解答,例如在人体肌肉中介导 IR 的特定神经酰胺和二酰基甘油的种类及其亚细胞定位。针对特定亚细胞器的定量脂质组学和蛋白质组学将有助于更好地定义病理性 IMCL 积累和 IR 的潜在机制。