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Hepatic lipid profile in mice fed a choline-deficient, low-methionine diet resembles human non-alcoholic fatty liver disease
Lipids in Health and Disease ( IF 3.9 ) Pub Date : 2020-12-09 , DOI: 10.1186/s12944-020-01425-1
Elisabeth M Haberl 1 , Rebekka Pohl 1 , Lisa Rein-Fischboeck 1 , Marcus Höring 2 , Sabrina Krautbauer 2 , Gerhard Liebisch 2 , Christa Buechler 1
Affiliation  

Emerging data support a role for lipids in non-alcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC) in humans. With experimental models such data can be challenged or validated. Mice fed a low-methionine, choline-deficient (LMCD) diet develop NASH and, when injected with diethylnitrosamine (DEN), HCC. Here, lipidomic analysis was used to elucidate whether the NASH and HCC associated lipid derangements resemble the lipid profile of the human disease. Lipids were measured in the liver of mice fed a control or a LMCD diet for 16 weeks. DEN was injected at young age to initiate hepatocarcinogenesis. DEN treatment associated changes of the lipid composition and the tumor lipidome were evaluated. LMCD diet fed mice accumulated ceramides and triacylglycerols in the liver. Phospholipids enriched with monounsaturated fatty acids were also increased, whereas hepatic cholesterol levels remained unchanged in the LMCD model. Phosphatidylcholine and lysophosphatidylcholine concentrations declined in the liver of LMCD diet fed mice. The changes of most lipids associated with LMCD diet feeding were similar between water and DEN injected mice. Several polyunsaturated (PU) diacylglycerol species were already low in the liver of DEN injected mice fed the control diet. Tumors developed in the liver of LMCD diet fed mice injected with DEN. The tumor specific lipid profile, however, did not resemble the decrease of ceramides and PU phospholipids, which was consistently described in human HCC. Triacylglycerols declined in the cancer tissues, which is in accordance with a low expression of lipogenic enzymes in the tumors. The LMCD model is suitable to study NASH associated lipid reprogramming. Hepatic lipid profile was modestly modified in the DEN injected mice suggesting a function of these derangements in carcinogenesis. Lipid composition of liver tumors did not resemble the human HCC lipidome, and most notably, lipogenesis and triacylglycerol levels were suppressed.

中文翻译:

喂食缺乏胆碱、低蛋氨酸饮食的小鼠的肝脏脂质谱类似于人类非酒精性脂肪肝

新出现的数据支持脂质在人类非酒精性脂肪性肝炎 (NASH) 和肝细胞癌 (HCC) 中的作用。通过实验模型,可以挑战或验证此类数据。喂食低蛋氨酸、胆碱缺乏 (LMCD) 饮食的小鼠会出现 NASH,并且在注射二乙基亚硝胺 (DEN) 时会出现 HCC。在这里,脂质组学分析用于阐明 NASH 和 HCC 相关的脂质紊乱是否与人类疾病的脂质特征相似。在喂食对照或 LMCD 饮食 16 周的小鼠的肝脏中测量脂质。在年轻时注射 DEN 以启动肝癌发生。评估了 DEN 治疗相关的脂质组成和肿瘤脂质组的变化。LMCD 饮食喂养的小鼠在肝脏中积累了神经酰胺和三酰甘油。富含单不饱和脂肪酸的磷脂也增加了,而在 LMCD 模型中肝脏胆固醇水平保持不变。LMCD 饮食喂养的小鼠肝脏中的磷脂酰胆碱和溶血磷脂酰胆碱浓度下降。大多数与 LMCD 饮食喂养相关的脂质变化在水和 DEN 注射小鼠之间相似。在喂食对照饮食的 DEN 注射小鼠的肝脏中,几种多不饱和 (PU) 二酰基甘油种类已经很低。用注射 DEN 的 LMCD 饮食喂养小鼠的肝脏中出现肿瘤。然而,肿瘤特异性脂质谱与神经酰胺和 PU 磷脂的减少不同,这在人类 HCC 中得到一致描述。三酰甘油在癌组织中下降,这与肿瘤中脂肪生成酶的低表达一致。LMCD 模型适用于研究 NASH 相关的脂质重编程。在注射 DEN 的小鼠中,肝脏脂质谱适度改变,表明这些紊乱在致癌作用中起作用。肝脏肿瘤的脂质组成与人类 HCC 脂质组不同,最值得注意的是,脂肪生成和三酰甘油水平受到抑制。
更新日期:2020-12-09
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