Phosphatidylethanolamines Are Associated with Nonalcoholic Fatty Liver Disease (NAFLD) in Obese Adults and Induce Liver Cell Metabolic Perturbations and Hepatic Stellate Cell Activation.
Phosphatidylethanolamines Are Associated with Nonalcoholic Fatty Liver Disease (NAFLD) in Obese Adults and Induce Liver Cell Metabolic Perturbations and Hepatic Stellate Cell Activation.
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DOI：
10.3390/ijms24021034
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发表时间：
2023-01-05
影响因子：
5.6
通讯作者：
Liu, Wanqing
中科院分区：
文献类型：
--
作者：
Shama, Samaa;Jang, Hyejeong;Wang, Xiaokun;Zhang, Yang;Shahin, Nancy Nabil;Motawi, Tarek Kamal;Kim, Seongho;Gawrieh, Samer;Liu, Wanqing
关键词：
磷脂(Pls)在非酒精性脂肪性肝病(NAFLD)发病机制中的作用尚不完全清楚。本研究通过研究疾病进展过程中血清磷脂成分的变化，以及评价特异性磷脂酰乙醇胺(PES)对体外FLD发展的影响，探讨PLS在肥胖者NAFLD进展中的作用。共有203名正在接受减肥手术的肥胖受试者参加了这项研究。组织学分正常对照组(C)80例，单纯肝脂肪变性(SS)93例，交界性非酒精性脂肪性肝炎(B-NASH)16例，进展性NASH(NASH)14例。采用全自动电喷雾电离串联质谱仪(ESI-MS/MS)分析血清PLs。用HepG2(肝癌细胞)和Lx2(永生化肝星状细胞)研究PL在NAFLD/NASH发生发展中的作用。几种PL及其相对比率与NAFLD的进展显著相关，尤其是那些涉及PE的PL。两种磷脂酰乙醇胺(PE(34：1)和PE(36：2))与HepG2细胞孵育后，细胞增殖受到明显抑制，线粒体质量和膜电位降低，脂质堆积和线粒体ROS生成减少。同时，两种PES处理Lx2细胞均显著增加细胞的活化和迁移。这些效应与与脂肪生成、脂质氧化、自噬、细胞凋亡、炎症和纤维化相关的基因表达水平的显著变化有关。因此，我们的研究表明，PES水平的升高增加了肥胖相关NAFLD的疾病进展的易感性，可能是通过对不同肝细胞功能的一系列因果影响。
Pathogenesis roles of phospholipids (PLs) in nonalcoholic fatty liver disease (NAFLD) remain incompletely understood. This study investigated the role of PLs in the progression of NAFLD among obese individuals via studying the alterations in serum PL composition throughout the spectrum of disease progression and evaluating the effects of specific phosphatidylethanolamines (PEs) on FLD development in vitro. A total of 203 obese subjects, who were undergoing bariatric surgery, were included in this study. They were histologically classified into 80 controls (C) with normal liver histology, 93 patients with simple hepatic steatosis (SS), 16 with borderline nonalcoholic steatohepatitis (B-NASH) and 14 with progressive NASH (NASH). Serum PLs were profiled by automated electrospray ionization tandem mass spectrometry (ESI-MS/MS). HepG2 (hepatoma cells) and LX2 (immortalized hepatic stellate cells or HSCs) were used to explore the roles of PL in NAFLD/NASH development. Several PLs and their relative ratios were significantly associated with NAFLD progression, especially those involving PE. Incubation of HepG2 cells with two phosphatidylethanolamines (PEs), PE (34:1) and PE (36:2), resulted in significant inhibition of cell proliferation, reduction of mitochondrial mass and membrane potential, induction of lipid accumulation and mitochondrial ROS production. Meanwhile, treatment of LX2 cells with both PEs markedly increased cell activation and migration. These effects were associated with a significant change in the expression levels of genes involved in lipogenesis, lipid oxidation, autophagy, apoptosis, inflammation, and fibrosis. Thus, our study demonstrated that elevated level of PEs increases susceptibility to the disease progression of obesity associated NAFLD, likely through a causal cascade of impacts on the function of different liver cells.
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影响因子：
5.6
作者：
Kanuri G;Bergheim I
通讯作者：
Bergheim I
影响因子：
6.1
作者：
Ma DW;Arendt BM;Hillyer LM;Fung SK;McGilvray I;Guindi M;Allard JP
通讯作者：
Allard JP
影响因子：
3.8
作者：
Devaiah, Shivakumar Pattada;Roth, Mary R.;Wang, Xuemin
通讯作者：
Wang, Xuemin
DOI：
10.1139/apnm-2012-0261
发表时间：
2013-03-01
期刊：
APPLIED PHYSIOLOGY NUTRITION AND METABOLISM-PHYSIOLOGIE APPLIQUEE NUTRITION ET METABOLISME
影响因子：
--
作者：
Arendt, Bianca M.;Ma, David W. L.;Allard, Johane P.
通讯作者：
Allard, Johane P.
影响因子：
4.4
作者：
Maurice, James;Manousou, Pinelopi
通讯作者：
Manousou, Pinelopi