Department of Biochemistry, College of Medicine, Gachon University, Incheon 21999, Korea.
Department of Life Science, Gachon University, Seongnam 13120, Korea.
Mol Cells. 2020 May 31;43(5):419-430. doi: 10.14348/molcells.2020.0054.
The liver is an important organ in the regulation of glucose and lipid metabolism. It is responsible for systemic energy homeostasis. When energy need exceeds the storage capacity in the liver, fatty acids are shunted into nonoxidative sphingolipid biosynthesis, which increases the level of cellular ceramides. Accumulation of ceramides alters substrate utilization from glucose to lipids, activates triglyceride storage, and results in the development of both insulin resistance and hepatosteatosis, increasing the likelihood of major metabolic diseases. Another sphingolipid metabolite, sphingosine 1-phosphate (S1P) is a bioactive signaling molecule that acts via S1P-specific G protein coupled receptors. It regulates many cellular and physiological events. Since an increase in plasma S1P is associated with obesity, it seems reasonable that recent studies have provided evidence that S1P is linked to lipid pathophysiology, including hepatosteatosis and fibrosis. Herein, we review recent findings on ceramides and S1P in obesity-mediated liver diseases and the therapeutic potential of these sphingolipid metabolites.
肝脏是调节葡萄糖和脂质代谢的重要器官。它负责全身能量稳态。当能量需求超过肝脏的储存能力时，脂肪酸被分流到非氧化鞘脂生物合成中，这会增加细胞神经酰胺的水平。神经酰胺的积累会改变从葡萄糖到脂质的底物利用，激活甘油三酯储存，导致胰岛素抵抗和肝脂肪变性的发展，增加发生主要代谢疾病的可能性。另一种鞘脂代谢物，鞘氨醇 1-磷酸（S1P）是一种生物活性信号分子，通过 S1P 特异性 G 蛋白偶联受体发挥作用。它调节许多细胞和生理事件。由于血浆 S1P 的增加与肥胖有关，因此最近的研究提供了证据表明 S1P 与脂质病理生理学有关，包括肝脂肪变性和纤维化，这似乎是合理的。本文综述了肥胖介导的肝脏疾病中神经酰胺和 S1P 的最新发现，以及这些鞘脂代谢物的治疗潜力。
