Department of Biochemistry and Molecular Biology, VCU School of Medicine and Massey Cancer Center, Richmond, VA 23298, USA.
Department of Biochemistry and Molecular Biology, VCU School of Medicine and Massey Cancer Center, Richmond, VA 23298, USA; Hunter Holmes McGuire VA Medical Center, Richmond, VA 23298, USA.
Cell Metab. 2021 Jul 6;33(7):1293-1306. doi: 10.1016/j.cmet.2021.06.006.
The bioactive sphingolipid metabolites ceramide and sphingosine-1-phosphate (S1P) are a recent addition to the lipids accumulated in obesity and have emerged as important molecular players in metabolic diseases. Here we summarize evidence that dysregulation of sphingolipid metabolism correlates with pathogenesis of metabolic diseases in humans. This review discusses the current understanding of how ceramide regulates signaling and metabolic pathways to exacerbate metabolic diseases and the Janus faces for its further metabolite S1P, the kinases that produce it, and the multifaceted and at times opposing actions of S1P receptors in various tissues. Gaps and limitations in current knowledge are highlighted together with the need to further decipher the full array of their actions in tissue dysfunction underlying metabolic pathologies, pointing out prospects to move this young field of research toward the development of effective therapeutics.
生物活性神经酰胺和鞘氨醇-1-磷酸（S1P）等神经鞘脂代谢物是肥胖症中积累的脂质的最新成员，它们已成为代谢性疾病中重要的分子参与者。在这里，我们总结了神经鞘脂代谢失调与人类代谢性疾病发病机制相关的证据。本综述讨论了目前对神经酰胺如何调节信号转导和代谢途径以加重代谢性疾病的理解，以及其进一步代谢产物 S1P、产生 S1P 的激酶、S1P 受体在各种组织中的多方面和有时相反的作用。强调了当前知识中的差距和局限性，以及需要进一步阐明它们在代谢病理基础组织功能障碍中的作用，指出了将这一新兴研究领域推向开发有效治疗方法的前景。
