Department of Physiology, University of Kentucky College of Medicine, Lexington, KY 40536, USA.
Biochimie. 2011 Jan;93(1):32-8. doi: 10.1016/j.biochi.2010.05.016. Epub 2010 May 31.
Palmitic acid is a saturated fat found in foods that lead to obesity, cardiovascular disease, and Type II diabetes. It is linked to the development of resistance to insulin stimulation in muscle, liver and other organs involved in glucose metabolism, which, in turn, underlines the onset of Type II diabetes. The cellular and molecular mechanisms of this insulin resistance are complex and not completely understood. This article is focused on the role of palmitic acid as a precursor in the synthesis of sphingolipids, a class of lipid molecules that participate in cellular stress response. Recent evidence had indicated that increased dietary supply of palmitate can stimulate the rate of sphingolipid synthesis in "lean" tissues and generate excessive amounts of sphingolipid metabolites that have a negative effect on the insulin signaling cascade. Many experimental results point to the existence of a causative link between sphingolipid synthesis, insulin response, and hyperglycemia. It is not yet clear, however whether ceramides or glycosphingolipids are involved as both have been implicated to be inhibitors of the insulin signaling cascade. Evidence for a coordinated regulation of sphingolipid and tri/diacylglycerol metabolism complicates further the delineation of a single mechanism of sphingolipid effect on glucose homeostasis.
软脂酸是一种在导致肥胖、心血管疾病和 2 型糖尿病的食物中发现的饱和脂肪。它与肌肉、肝脏和其他参与葡萄糖代谢的器官对胰岛素刺激的抵抗力的发展有关,这反过来又强调了 2 型糖尿病的发生。这种胰岛素抵抗的细胞和分子机制很复杂,尚未完全了解。本文重点介绍软脂酸作为鞘脂合成前体的作用,鞘脂是参与细胞应激反应的一类脂质分子。最近的证据表明,饮食中软脂酸盐的供应增加可以刺激“瘦”组织中鞘脂合成的速度,并产生大量对胰岛素信号级联有负面影响的鞘脂代谢物。许多实验结果表明,鞘脂合成、胰岛素反应和高血糖之间存在因果关系。然而,尚不清楚神经酰胺或糖鞘脂是否参与其中,因为它们都被认为是胰岛素信号级联的抑制剂。鞘脂和三酰基甘油代谢的协调调控进一步复杂化了阐明鞘脂对葡萄糖稳态的单一作用机制。