Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, VA, USA.
Department of Biology, Virginia Commonwealth University, Richmond, VA, USA.
Methods Mol Biol. 2022;2455:279-303. doi: 10.1007/978-1-0716-2128-8_22.
The relationship between sphingolipid levels and NAFLD pathology has been recognized for some time. Numerous studies using pharmacological and genetic approaches in vitro and in animal models of NAFLD have demonstrated that modifications to sphingolipid metabolism can attenuate various facets of NAFLD pathology. However, a more precise understanding of the role of sphingolipids and NAFLD pathology is essential to creating therapeutics that target this pathway. This chapter touches on the scale and variety of sphingolipid metabolites at play in NAFLD, which vary widely in their chemical structures and biological functions. With advances in liquid chromatography and tandem mass spectrometry approaches, each of thousands of individual sphingolipid species and sphingolipid metabolites can be identified and precisely quantified. These approaches are beginning to reveal specific sub-classes and species of sphingolipids that change in NAFLD, and as such, enzymes that generate them can be identified and potentially serve as therapeutic targets. Advances in lipidomics technology have been, and will continue to be, critical to these gains in our understanding of NAFLD.
一段时间以来，人们已经认识到神经酰胺水平与 NAFLD 病理之间的关系。大量使用药理学和遗传学方法在体外和 NAFLD 动物模型中的研究表明，神经酰胺代谢的改变可以减轻 NAFLD 病理的各个方面。然而，为了开发针对该途径的治疗方法，更精确地了解神经酰胺的作用和 NAFLD 病理是至关重要的。本章涉及在 NAFLD 中起作用的神经酰胺代谢物的规模和种类，它们在化学结构和生物学功能上差异很大。随着液相色谱和串联质谱方法的进步，数千种单个神经酰胺种类和神经酰胺代谢物中的每一种都可以被鉴定和精确量化。这些方法开始揭示在 NAFLD 中发生变化的特定神经酰胺亚类和种类，因此，可以鉴定产生它们的酶，并可能将其作为治疗靶点。脂质组学技术的进步已经并将继续对我们理解 NAFLD 的这些进展至关重要。
