Seubnooch Patcharamon, Montani Matteo, Tsouka Sofia, Claude Emmanuelle, Rafiqi Umara, Perren Aurel, Dufour Jean-Francois, Masoodi Mojgan
Institute of Clinical Chemistry, Inselspital, Bern University Hospital, Bern, Switzerland.
Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
JHEP Rep. 2023 Mar 9;5(6):100725. doi: 10.1016/j.jhepr.2023.100725. eCollection 2023 Jun.
BACKGROUND & AIMS: Lipid metabolism plays an important role in liver pathophysiology. The liver lobule asymmetrically distributes oxygen and nutrition, resulting in heterogeneous metabolic functions. Periportal and pericentral hepatocytes have different metabolic functions, which lead to generating liver zonation. We developed spatial metabolic imaging using desorption electrospray ionisation mass spectrometry to investigate lipid distribution across liver zonation with high reproducibility and accuracy.
Fresh frozen livers from healthy mice with control diet were analysed using desorption electrospray ionisation mass spectrometry imaging. Imaging was performed at 50 μm × 50 μm pixel size. Regions of interest (ROIs) were manually created by co-registering with histological data to determine the spatial hepatic lipids across liver zonation. The ROIs were confirmed by double immunofluorescence. The mass list of specific ROIs was automatically created, and univariate and multivariate statistical analysis were performed to identify statistically significant lipids across liver zonation.
A wide range of lipid species was identified, including fatty acids, phospholipids, triacylglycerols, diacylglycerols, ceramides, and sphingolipids. We characterised hepatic lipid signatures in three different liver zones (periportal zone, midzone, and pericentral zone) and validated the reproducibility of our method for measuring a wide range of lipids. Fatty acids were predominantly detected in the periportal region, whereas phospholipids were distributed in both the periportal and pericentral zones. Interestingly, phosphatidylinositols, PI(36:2), PI(36:3), PI(36:4), PI(38:5), and PI(40:6) were located predominantly in the midzone (zone 2). Triacylglycerols and diacylglycerols were detected mainly in the pericentral region. triacylglycerol biosynthesis appeared to be the most influenced pathway across the three zones.
The ability to accurately assess zone-specific hepatic lipid distribution in the liver could lead to a better understanding of lipid metabolism during the progression of liver disease.
Zone-specific hepatic lipid metabolism could play an important role in lipid homoeostasis during disease progression. Herein, we defined the zone-specific references of hepatic lipid species in the three liver zones using molecular imaging. The triacylglycerol biosynthesis was highlighted as the most influenced pathway across the three zones.
脂质代谢在肝脏病理生理学中起着重要作用。肝小叶不对称地分布氧气和营养物质，导致代谢功能的异质性。汇管区和中央静脉周围的肝细胞具有不同的代谢功能，从而形成肝脏的分区。我们开发了一种利用解吸电喷雾电离质谱的空间代谢成像技术，以高重现性和准确性研究肝脏分区内的脂质分布。
使用解吸电喷雾电离质谱成像分析来自食用对照饮食的健康小鼠的新鲜冷冻肝脏。成像在50μm×50μm像素大小下进行。通过与组织学数据共同配准手动创建感兴趣区域（ROI），以确定整个肝脏分区的肝脏空间脂质。通过双重免疫荧光确认ROI。自动创建特定ROI的质量列表，并进行单变量和多变量统计分析，以识别整个肝脏分区中具有统计学意义的脂质。
鉴定出了多种脂质种类，包括脂肪酸、磷脂、三酰甘油、二酰甘油、神经酰胺和鞘脂。我们对三个不同肝脏区域（汇管区、中区和中央静脉周围区）的肝脏脂质特征进行了表征，并验证了我们测量多种脂质方法的重现性。脂肪酸主要在汇管区检测到，而磷脂分布在汇管区和中央静脉周围区。有趣的是，磷脂酰肌醇PI(36:2)、PI(36:3)、PI(36:4)、PI(38:5)和PI(40:6)主要位于中区（2区）。三酰甘油和二酰甘油主要在中央静脉周围区域检测到。三酰甘油生物合成似乎是三个区域中受影响最大的途径。
准确评估肝脏中特定区域的肝脏脂质分布的能力可能有助于更好地理解肝脏疾病进展过程中的脂质代谢。
特定区域的肝脏脂质代谢可能在疾病进展过程中的脂质稳态中起重要作用。在此，我们使用分子成像定义了三个肝脏区域中肝脏脂质种类的特定区域参考。三酰甘油生物合成被突出显示为三个区域中受影响最大的途径。
