Lipidomic profiling of the hepatic esterified fatty acid composition in diet-induced nonalcoholic fatty liver disease in genetically diverse Collaborative Cross mice.
Lipidomic profiling of the hepatic esterified fatty acid composition in diet-induced nonalcoholic fatty liver disease in genetically diverse Collaborative Cross mice.
复制标题
饮食诱导的遗传多样性协作杂交小鼠中肝酯化的脂肪酸组成的脂质组分析。
DOI：
10.1016/j.jnutbio.2022.109108
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发表时间：
2022-11
影响因子：
5.6
通讯作者：
Pogribny, Igor P.
中科院分区：
文献类型：
--
作者：
Nagumalli, Suresh K.;Willett, Rose A.;de Conti, Aline;Tryndyak, Volodymyr P.;Avigan, Mark I.;da Costa, Goncalo Gamboa;Beland, Frederick A.;Rusyn, Ivan;Pogribny, Igor P.
关键词：
非酒精性脂肪性肝病（NAFLD）是慢性肝病最常见的形式之一，其特征在于肝细胞中脂质物质的过度积累。最近的研究表明，除了总脂质量外，脂质组成的变化是肝脏脂毒性的决定因素。采用超高效液相色谱-电喷雾串联质谱联用技术，我们分析了24株雄性和雌性协作杂交（CC）小鼠饲喂高脂肪/高糖（HF/HS）饮食12周的酯化脂肪酸组成。在HF/HS饮食后的所有菌株中发现脂质组成的变化，最显着的特点是单不饱和脂肪酸（MUFA）的增加和多不饱和脂肪酸（PUFA）的减少。在胆碱和叶酸缺乏（CFD）的NAFLD小鼠模型以及用游离脂肪酸体外处理的肝细胞中观察到MUFA和PUFA的类似变化。脂肪酸组成的分析显示，变化伴随着MUFA生成SCD 1酶的估计活性的增加和PUFA生成FADS 1和FADS 2酶的活性的减少，如MUFA产物C18：1的增加和PUFA产物C18：2和C20：4的减少所示。PUFA/MUFA比值与喂食HF/HS饲料的雄性和雌性CC小鼠中的脂质蓄积呈负相关，与喂食CFD饲料的NAFLD小鼠模型中的肝损伤形态学标志物呈负相关。这些结果表明，不同的NAFLD模型的特征在于酯化脂肪酸组成的相似变化，并且PUFA/MUFA比率的改变可以作为NAFLD严重程度的诊断标志物。
Nonalcoholic fatty liver disease (NAFLD), one of the most common forms of chronic liver disease, is characterized by the excessive accumulation of lipid species in hepatocytes. Recent studies have indicated that in addition to the total lipid quantities, changes in lipid composition are a determining factor in hepatic lipotoxicity. Using ultra-high performance liquid chromatography coupled with electrospray tandem mass spectrometry, we analyzed the esterified fatty acid composition in 24 strains of male and female Collaborative Cross (CC) mice fed a high fat/high sucrose (HF/HS) diet for 12 weeks. Changes in lipid composition were found in all strains after the HF/HS diet, most notably characterized by increases in monounsaturated fatty acids (MUFA) and decreases in polyunsaturated fatty acids (PUFA). Similar changes in MUFA and PUFA were observed in a choline- and folate-deficient (CFD) mouse model of NAFLD, as well as in hepatocytes treated in vitro with free fatty acids. Analysis of fatty acid composition revealed that alterations were accompanied by an increase in the estimated activity of MUFA generating SCD1 enzyme and a decrease in the activity of PUFA generating FADS1 and FADS2 enzymes as indicated by an increase in the MUFA product, C18:1, and a decrease in the PUFA products, C18:2 and C20:4. PUFA/MUFA ratios were inversely correlated with lipid accumulation in male and female CC mice fed the HF/HS diet and with morphological markers of hepatic injury in the CFD diet-fed mouse model of NAFLD. These results demonstrate that different models of NAFLD are characterized by similar changes in the esterified fatty acid composition and that alterations in PUFA/MUFA ratios may serve as a diagnostic marker for NAFLD severity.
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影响因子：
82.9
作者：
Friedman SL;Neuschwander-Tetri BA;Rinella M;Sanyal AJ
通讯作者：
Sanyal AJ
DOI：
10.1096/fj.202000194r
发表时间：
2020-06
期刊：
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
影响因子：
--
作者：
de Conti A;Tryndyak V;Willett RA;Borowa-Mazgaj B;Watson A;Patton R;Khare S;Muskhelishvili L;Olson GR;Avigan MI;Cerniglia CE;Ross SA;Sanyal AJ;Beland FA;Rusyn I;Pogribny IP
通讯作者：
Pogribny IP
影响因子：
9.8
作者：
Buzzetti, Elena;Pinzani, Massimo;Tsochatzis, Emmanuel A.
通讯作者：
Tsochatzis, Emmanuel A.
影响因子：
6
作者：
Araya, J;Rodrigo, R;Poniachik, J
通讯作者：
Poniachik, J
影响因子：
5.8
作者：
Le, Sebastien;Josse, Julie;Husson, Francois
通讯作者：
Husson, Francois