Identification cholesterol metabolites altered before the onset of nonalcoholic steatohepatitis by targeted metabolomics
Identification cholesterol metabolites altered before the onset of nonalcoholic steatohepatitis by targeted metabolomics
复制标题
通过靶向代谢组学鉴定非酒精性脂肪性肝炎发病前改变的胆固醇代谢物
DOI：
10.1016/j.bbalip.2022.159135
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Mano Nariyasu
中科院分区：
文献类型：
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作者：
Shoji Saori;Maekawa Masamitsu;Ogura Jiro;Sato Toshihiro;Mano Nariyasu
非酒精性脂肪性肝炎（NASH）是一种症状类似于无酒精摄入的酒精性肝脏炎症的疾病。由于尚未建立有效的治疗策略，因此需要详细了解其病理进展机制。本研究以胆固醇代谢产物为研究对象，探讨其与NASH早期病理进展的关系。首先，对胆汁酸和甾醇的LC/MS/MS方法进行优化和验证。接下来，通过喂养胆碱缺乏、甲硫氨酸减少的高脂肪饮食建立NASH模型小鼠，并测量肝脏胆固醇代谢物的水平。结果，在NASH发病前，桥甾醇、4β-羟基胆固醇、菜油甾醇、谷甾醇、二级胆汁酸如牛磺脱氧胆酸显著降低，最高达NASH模型组的1/38。自氧化产生的甾醇显著增加2- 5倍，各种初级胆汁酸如结合β-鼠胆酸和胆酸显著增加2- 7倍。这些参与炎症诱导和NASH解毒的代谢改变可能有助于未来发现早期诊断生物标志物。
Nonalcoholic steatohepatitis (NASH) is a disease with symptoms similar to those of alcoholic liver inflammation without alcohol intake. As an effective treatment strategy has not been established for this disease, a detailed understanding of the pathological progression mechanism is required. We focused on cholesterol metabolites, which are suspected to regulate NASH pathology, and investigated their relationship with the pathological progression in the early stages of NASH.First, the LC/MS/MS methods for bile acids and sterols were optimized and validated. Next, NASH model mice were established by feeding a choline-deficient, methionine-reduced high-fat diet, and the levels of hepatic cholesterol metabolites were measured. As a result, before the onset of NASH, desmosterol, 4β-hydroxycholesterol, campesterol, sitosterol, secondary bile acids such as taurodeoxycholic acid significantly decreased by up to 1/38 of NASH model group. Autoxidation-generated sterols significantly increased 2- to 5-fold, and various primary bile acids such as conjugated β-muricholic acids and cholic acids significantly increased 2- to 7-fold.In this study, the levels of cholesterol metabolites changed in the before the onset of NASH. These metabolic alterations involved in inflammation induction and detoxification for NASH may help the discovery of early diagnostic biomarkers in the future.