Biomedical Imaging Center, Pontificia Universidad Católica de Chile, Santiago, Chile; ANID, Millennium Science Initiative Program, Millennium Nucleus for Cardiovascular Magnetic Resonance, Santiago, Chile; Instituto de Ciencias de la Ingeniería, Universidad de O'Higgins, Rancagua, Chile.
Faculty of Chemistry and Pharmacy, Pontificia Universidad Católica de Chile, Santiago, Chile; Research Center for Nanotechnology and Advanced Materials CIEN-UC, Pontificia Universidad Católica de Chile, Santiago, Chile; Institute for Biological and Medical Engineering, Schools of Engineering, Medicine and Biological Sciences, Pontificia Universidad Católica de Chile, Santiago, Chile.
Ann Hepatol. 2021 Nov-Dec;25:100358. doi: 10.1016/j.aohep.2021.100358. Epub 2021 May 4.
Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of liver abnormalities including steatosis, steatohepatitis, fibrosis, and cirrhosis. Liver biopsy remains the gold standard method to determine the disease stage in NAFLD but is an invasive and risky procedure. Studies have previously reported that changes in intrahepatic fatty acids (FA) composition are related to the progression of NAFLD, mainly in its early stages. The aim of this study was to characterize the liver FA composition in mice fed a Choline-deficient L-amino-defined (CDAA) diet at different stages of NAFLD using magnetic resonance spectroscopy (MRS).
We used in-vivo MRS to perform a longitudinal characterization of hepatic FA changes in NAFLD mice for 10 weeks. We validated our findings with ex-vivo MRS, gas chromatography-mass spectrometry and histology.
In-vivo and ex-vivo results showed that livers from CDAA-fed mice exhibit a significant increase in liver FA content as well as a change in FA composition compared with control mice. After 4 weeks of CDAA diet, a decrease in polyunsaturated and an increase in monounsaturated FA were observed. These changes were associated with the appearance of early stages of steatohepatitis, confirmed by histology (NAFLD Activity Score (NAS) = 4.5). After 10 weeks of CDAA-diet, the liver FA composition remained stable while the NAS increased further to 6 showing a combination of early and late stages of steatohepatitis.
Our results suggest that monitoring lipid composition in addition to total water/fat with MRS may yield additional insights that can be translated for non-invasive stratification of high-risk NAFLD patients.
非酒精性脂肪性肝病（NAFLD）包括一系列肝脏异常，包括脂肪变性、脂肪性肝炎、纤维化和肝硬化。肝活检仍然是确定 NAFLD 疾病阶段的金标准方法，但它是一种侵入性和有风险的程序。先前的研究报告称，肝内脂肪酸（FA）组成的变化与 NAFLD 的进展有关，主要是在其早期阶段。本研究的目的是使用磁共振波谱（MRS）在不同阶段的 NAFLD 小鼠中描述胆碱缺乏 L-氨基酸定义（CDAA）饮食喂养的小鼠的肝 FA 组成。
我们使用体内 MRS 对 NAFLD 小鼠进行 10 周的肝 FA 变化进行纵向特征描述。我们使用体外 MRS、气相色谱-质谱和组织学验证了我们的发现。
体内和体外结果表明，与对照小鼠相比，CDAA 喂养的小鼠的肝脏 FA 含量显著增加，并且 FA 组成发生变化。在 CDAA 饮食 4 周后，观察到多不饱和 FA 减少和单不饱和 FA 增加。这些变化与组织学上观察到的早期脂肪性肝炎相一致（NAFLD 活动评分（NAS）= 4.5）。在 CDAA 饮食 10 周后，肝脏 FA 组成保持稳定，而 NAS 进一步增加至 6，显示出早期和晚期脂肪性肝炎的结合。
我们的结果表明，除了使用 MRS 监测总水/脂肪外，监测脂质组成可能会提供额外的见解，这些见解可以转化为非侵入性高危 NAFLD 患者的分层。
