Department of Nutrition and Integrative Physiology, Diabetes and Metabolism Research Center, University of Utah, Salt Lake City, UT.
Department of Nutrition and Integrative Physiology, Diabetes and Metabolism Research Center, University of Utah, Salt Lake City, UT.
Semin Nephrol. 2022 May;42(3):151281. doi: 10.1016/j.semnephrol.2022.10.007. Epub 2022 Nov 18.
Altered lipid metabolism is a characteristic feature and potential driving factor of acute kidney injury (AKI). Of the lipids that accumulate in injured renal tissues, ceramides are potent regulators of metabolism and cell fate. Up-regulation of ceramide synthesis is a common feature shared across several AKI etiologies in vitro and in vivo. Furthermore, ceramide accumulation is an early event in the natural history of AKI that precedes cell death and organ dysfunction. Emerging evidence suggests that inhibition of ceramide accumulation may improve renal outcomes in several models of AKI. This review examines the landscape of ceramide metabolism and regulation in the healthy and injured kidney. Furthermore, we discuss the body of literature regarding ceramides as therapeutic targets for AKI and consider potential mechanisms by which ceramides drive kidney pathogenesis.
脂质代谢改变是急性肾损伤 (AKI) 的特征性表现和潜在驱动因素。在损伤的肾组织中积累的脂质中,神经酰胺是代谢和细胞命运的有效调节剂。在体外和体内,几种 AKI 病因中都存在神经酰胺合成上调这一共同特征。此外,神经酰胺积累是 AKI 自然史中的早期事件,早于细胞死亡和器官功能障碍。新出现的证据表明,抑制神经酰胺积累可能会改善几种 AKI 模型的肾脏预后。本综述检查了健康和受损肾脏中神经酰胺代谢和调节的概况。此外,我们还讨论了关于神经酰胺作为 AKI 治疗靶点的文献,并考虑了神经酰胺驱动肾脏发病机制的潜在机制。