Institute of Clinical Chemistry, Inselspital, Bern University Hospital, Bern, Switzerland; Graduate School for Cellular and Biomedical Sciences, University of Bern, Switzerland.
Institute of Tissue Medicine and Pathology, University of Bern, Bern, Switzerland.
J Lipid Res. 2024 Sep;65(9):100599. doi: 10.1016/j.jlr.2024.100599. Epub 2024 Jul 18.
Alteration in lipid metabolism plays a pivotal role in developing metabolic dysfunction-associated steatohepatitis (MASH). However, our understanding of alteration in lipid metabolism across liver zonation in MASH remains limited. Within this study, we investigated MASH-associated zone-specific lipid metabolism in a diet and chemical-induced MASH mouse model. Spatial lipidomics using mass spectrometry imaging in a MASH mouse model revealed 130 lipids from various classes altered across liver zonation and exhibited zone-specific lipid signatures in MASH. Triacylglycerols, diacylglycerols, sphingolipids and ceramides showed distinct zone-specific changes and re-distribution from pericentral to periportal localization in MASH. Saturated and monounsaturated fatty acids (FA) were the primary FA composition of increased lipids in MASH, while polyunsaturated FAs were the major FA composition of decreased lipids. We observed elevated fibrosis in the periportal region, which could be the result of observed metabolic alteration across zonation. Our study provides valuable insights into zone-specific hepatic lipid metabolism and demonstrates the significance of spatial lipidomics in understanding liver lipid metabolism. Identifying unique lipid distribution patterns may offer valuable insights into the pathophysiology of MASH and facilitate the discovery of diagnostic markers associated with liver zonation.
脂质代谢的改变在代谢相关脂肪性肝炎（MASH）的发生发展中起着关键作用。然而，我们对 MASH 中肝区带脂质代谢改变的认识仍然有限。在本研究中，我们在饮食和化学诱导的 MASH 小鼠模型中研究了与 MASH 相关的特定区域的脂质代谢。在 MASH 小鼠模型中使用质谱成像进行空间脂质组学分析，揭示了 130 种来自不同类别的脂质在肝区带中发生改变，并在 MASH 中表现出特定区域的脂质特征。甘油三酯、二酰基甘油、鞘脂和神经酰胺在 MASH 中表现出明显的特定区域变化和从中央静脉到门脉周围的重新分布。饱和脂肪酸和单不饱和脂肪酸（FA）是 MASH 中增加脂质的主要 FA 组成，而多不饱和 FAs 是减少脂质的主要 FA 组成。我们观察到门脉周围区域纤维化增加，这可能是区带间观察到的代谢改变的结果。我们的研究提供了对特定区域肝脂质代谢的有价值的见解，并展示了空间脂质组学在理解肝脏脂质代谢中的重要性。确定独特的脂质分布模式可能为 MASH 的病理生理学提供有价值的见解，并有助于发现与肝区带相关的诊断标志物。
