<br>CDAHFD 诱导的小鼠模型在肝磷脂酰胆碱和酰基肉碱的代谢中模拟人类 NASH,Food & Function

当前位置： X-MOL 学术 › Food Funct. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

CDAHFD 诱导的小鼠模型在肝磷脂酰胆碱和酰基肉碱的代谢中模拟人类 NASH
Food & Function ( IF 5.1 ) Pub Date : 2024-02-27 , DOI: 10.1039/d3fo05111k
Jie Yang ₁ , Manyun Dai ₂ , Ying Wang ₂ , Zheng Yan ₂ , Shuqi Mao ₁ , Aiming Liu ₂ , Caide Lu ₁

Affiliation

非酒精性脂肪性肝炎 (NASH) 是一系列与脂质代谢紊乱相关的疾病的肝脏表现。需要探索模仿人类 NASH 的理想动物模型，以更好地了解发病机制。最近已使用缺乏胆碱、 L-氨基酸限定的高脂肪饮食（CDAHFD）来诱导 NASH 模型，但其优点尚未确立。 NASH模型的诱导使用著名的传统蛋氨酸和胆碱缺乏（MCD）饮食5周，以及最近使用的CDAHFD 3周。分析肝脏表型以评估与 NASH 相关的标志物的差异。脂质组学和代谢分析用于研究饮食方案对肝脏脂质组的影响。 CDAHFD 比 MCD 诱导更强的 NASH 反应，包括脂质沉积、肝损伤、炎症、胆汁酸超负荷和肝细胞增殖。 CDAHFD 和 MCD 诱导的 NASH 模型之间的肝脏脂质组存在显着差异。特别是，CDAHFD 降低了肝脏中磷脂酰胆碱（PC）和酰基肉碱（AC）的水平，这得到了代谢分析的支持，并且符合人类 NASH 的趋势。从病理学角度来看，CDAHFD 可以有效诱导比传统 MCD 更接近人类的 NASH 模型。 CDAHFD 治疗小鼠的肝脏 PC、AC 及其代谢均下调，与人类 NASH 相似。

"点击查看英文标题和摘要"

A CDAHFD-induced mouse model mimicking human NASH in the metabolism of hepatic phosphatidylcholines and acyl carnitines

Non-alcoholic steatohepatitis (NASH) is the hepatic manifestation of a cluster of conditions associated with lipid metabolism disorders. Ideal animal models mimicking the human NASH need to be explored to better understand the pathogenesis. A choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) has recently been used to induce the NASH model, but the advantages are not established. NASH models were induced using the well-known traditional methionine- and choline-deficient (MCD) diet for 5 weeks and the recently used CDAHFD for 3 weeks. Liver phenotypes were analyzed to evaluate the differences in markers related to NASH. Lipidomics and metabolism analyses were used to investigate the effects of dietary regimens on the lipidome of the liver. The CDAHFD induced stronger NASH responses than the MCD, including lipid deposition, liver injury, inflammation, bile acid overload and hepatocyte proliferation. A significant difference in the hepatic lipidome was revealed between the CDAHFD and MCD-induced NASH models. In particular, the CDAHFD reduced the hepatic levels of phosphatidylcholines (PCs) and acylcarnitines (ACs), which was supported by the metabolism analysis and in line with the tendency of human NASH. Pathologically, the CDAHFD could effectively induce a more human-like NASH model over the traditional MCD. The hepatic PCs, ACs and their metabolism in CDAHFD-treated mice were down-regulated, similar to those in human NASH.

更新日期：2024-02-27

点击分享查看原文

点击收藏

阅读更多本刊新发论文本刊介绍/投稿指南