Kaempferol Alleviates Steatosis and Inflammation During Early Non-Alcoholic Steatohepatitis Associated With Liver X Receptor α-Lysophosphatidylcholine Acyltransferase 3 Signaling Pathway.
Kaempferol Alleviates Steatosis and Inflammation During Early Non-Alcoholic Steatohepatitis Associated With Liver X Receptor α-Lysophosphatidylcholine Acyltransferase 3 Signaling Pathway.
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山奈酚可减轻与肝脏 X 受体 α-溶血磷脂酰胆碱酰基转移酶 3 信号通路相关的早期非酒精性脂肪性肝炎期间的脂肪变性和炎症
DOI：
10.3389/fphar.2021.690736
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发表时间：
2021
影响因子：
5.6
通讯作者：
Ji G
中科院分区：
文献类型：
--
作者：
Xiang H;Shao M;Lu Y;Wang J;Wu T;Ji G
研究背景：山奈酚（Kaempferol，KP）具有抗炎、抗氧化、抗衰老、保护心血管等多种生物学作用。KP是否对非酒精性脂肪性肝炎（NASH）有治疗作用，详细机制目前尚不清楚。本研究旨在通过体内外实验探讨KP治疗NASH的作用机制。研究方法：1）体内实验：在高脂饮食（HFD）诱导的C57 BL/6 NASH小鼠模型中，以20 mg/kg/天的剂量通过灌胃给予KP。2)体外实验：采用棕榈酸/油酸（PA/OA，0.375/0.75 mM）干预HepG 2和AML 12细胞，建立脂肪变性细胞模型。体外实验采用低（20 μmol/L）、中（40 μmol/L）和高（60 μmol/L）三种浓度的KP。RT-qPCR和Western blot检测LXRα-LPCAT 3-ERS通路相关分子的mRNA和蛋白表达。结果如下：在NASH小鼠模型中，KP可显著降低LXRα、LPCAT 3和ERS相关因子PERK、eIF 2 α、ATF 6、ATF 4、XBP 1、CHOP、IRE 1 α和GRP 78的表达。在PA/OA诱导的细胞模型中，KP可降低甘油三酯和脂滴含量，并降低LXR α、LPCAT 3和ERS相关因子PERK、eIF 2 α、ATF 6、ATF 4、XBP 1、CHOP、IRE 1 α和GRP 78的表达。结论：KP可能通过降低LXRα和LPCAT 3的表达，改善ERS，减轻肝脏脂肪变性和炎症反应。
Background: Kaempferol (KP) has a variety of biological effects such as anti-inflammatory, anti-oxidant, anti-aging and cardiovascular protection. Whether KP has a therapeutic effect on non-alcoholic steatohepatitis (NASH), and the detailed mechanism is currently unclear. This study aims to explore the mechanism of KP in the treatment of NASH through in vivo and in vitro experiments. Methods: 1) In vivo experiment: In the C57BL/6 NASH mice model induced by high fat diet (HFD), KP was administered by gavage at a dose of 20 mg/kg/day. 2) In vitro experiment: Palmitic acid/Oleic acid (PA/OA, 0.375/0.75 mM) was used to intervene HepG2 and AML12 cells to establish a steatosis cell model. Three concentrations of KP, low (20 μmol/L), medium (40 μmol/L) and high (60 μmol/L) were used in vitro. The mRNA and protein expression of related molecules involved in LXRα-LPCAT3-ERS pathway were detected using RT-qPCR and Western blot. Results: In the NASH mouse model, KP can significantly reduce the expression of LXRα, LPCAT3 and ERS-related factors PERK, eIF2α, ATF6, ATF4, XBP1, CHOP, IRE1α and GRP78. In the PA/OA-induced cell model, KP could decrease the content of triglyceride and lipid droplets, and also decrease the expression of LXR α, LPCAT3 and ERS related factors PERK, eIF2α, ATF6, ATF4, XBP1, CHOP, IRE1α and GRP78. Conclusion: KP may decrease the expression level of LXRα and LPCAT3, thus improve ERS and reduce hepatic steatosis and inflammation.
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髓样细胞中溶物磷脂酰胆碱转移酶3的缺失会在高脂饮食后恶化肝脂肪变性。
影响因子：
6.5
作者：
Bourgeois T;Jalil A;Thomas C;Magnani C;Le Guern N;Gautier T;Pais de Barros JP;Bergas V;Choubley H;Mazzeo L;Menegaut L;Josiane Lebrun L;Van Dongen K;Xolin M;Jourdan T;Buch C;Labbé J;Saas P;Lagrost L;Masson D;Grober J
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82.9
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Friedman SL;Neuschwander-Tetri BA;Rinella M;Sanyal AJ
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Sanyal AJ
影响因子：
6.1
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Kouhestani S;Jafari A;Babaei P
通讯作者：
Babaei P
影响因子：
2.4
作者：
Lee, Bonggi;Kwon, Misung;Kim, Hyeung-Rak
通讯作者：
Kim, Hyeung-Rak
影响因子：
13.5
作者：
Lebeaupin, Cynthia;Vallee, Deborah;Bailly-Maitre, Beatrice
通讯作者：
Bailly-Maitre, Beatrice