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IF 5.6 2区生物学

International Journal of Molecular Sciences Pub Date : 2024-10-09 DOI:10.3390/ijms251910855

Wen Fan, Maoxing Pan, Chuiyang Zheng, Haiyan Shen, Dajin Pi, Qingliang Song, Zheng Liang, Jianwei Zhen, Jinyue Pan, Lianghao Liu, Qinhe Yang, Yupei Zhang

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引用次数: 0

摘要

Leonurine 是唇形科植物 Leonurus japonicus Houtt.特有的一种天然产物，因其具有抗氧化应激、抗细胞凋亡、抗纤维化和调节代谢的特性而备受关注。此外，它还通过多种生物学机制在预防和治疗非酒精性脂肪肝（NAFLD）中发挥着重要作用，但其作用机制仍有待阐明。因此，本研究旨在初步探讨亮丙瑞林在非酒精性脂肪肝中的作用机制。小鼠随机分为四组：正常对照组（NC）、模型组（M）、利奥那林治疗组（LH）和非诺贝特治疗组（FB）。非酒精性脂肪肝模型通过高脂高糖饮食（HFHSD）诱导12周，12周后观察肝脏病理变化和生化指标。转录组分析结果表明，亮丙瑞林干预可逆转高脂高糖饮食诱导的肝组织中脂肪代谢相关基因的变化，如硬脂酰-CoA去饱和酶1（Scd1）、精胺合成酶（Sms）、AP-1转录因子亚基（Fos）、氧基甾醇结合蛋白5（Osbpl5）和FK506结合蛋白5（Fkbp5）。京都基因组百科全书》（KEGG）富集分析结果表明，利血平可能通过AMP激活蛋白激酶（AMPK）信号通路发挥降脂作用。肝脏脂质体分析表明，利奥嘌呤可改变与脂肪酰基（FAs）和甘油磷脂（GPs）相关的脂质分子的丰度，如TxB3、肉碱C12-OH、肉碱C18:1-OH和LPC（20:3/0:0）。分子生物学实验和分子对接技术验证了利奥那林可通过α-1A肾上腺素能受体（ADRA1a）/AMPK/SCD1轴改善肝脏脂质代谢。综上所述，本研究探讨了亮菌甲素通过ADRA1a/AMPK/SCD1轴抑制肝脂质合成从而改善非酒精性脂肪肝的机制。

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Leonurine Inhibits Hepatic Lipid Synthesis to Ameliorate NAFLD via the ADRA1a/AMPK/SCD1 Axis.

Leonurine is a natural product unique to the Lamiaceae plant Leonurus japonicus Houtt., and it has attracted attention due to its anti-oxidative stress, anti-apoptosis, anti-fibrosis, and metabolic regulation properties. Also, it plays an important role in the prevention and treatment of nonalcoholic fatty liver disease (NAFLD) through a variety of biological mechanisms, but its mechanism of action remains to be elucidated. Therefore, this study aims to preliminarily explore the mechanisms of action of leonurine in NAFLD. Mice were randomly divided into four groups: the normal control (NC) group, the Model (M) group, the leonurine treatment (LH) group, and the fenofibrate treatment (FB) group. The NAFLD model was induced by a high-fat high-sugar diet (HFHSD) for 12 weeks, and liver pathological changes and biochemical indices were observed after 12 weeks. Transcriptomic analysis results indicated that leonurine intervention reversed the high-fat high-sugar diet-induced changes in lipid metabolism-related genes such as stearoyl-CoA desaturase 1 (Scd1), Spermine Synthase (Sms), AP-1 Transcription Factor Subunit (Fos), Oxysterol Binding Protein Like 5 (Osbpl5), and FK506 binding protein 5 (Fkbp5) in liver tissues. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis results suggest that leonurine may exert its lipid-lowering effects through the AMP-activated protein kinase (AMPK) signaling pathway. Liver lipidomic analysis showed that leonurine could alter the abundance of lipid molecules related to fatty acyl (FAs) and glycerophospholipids (GPs) such as TxB3, carnitine C12-OH, carnitine C18:1-OH, and LPC (20:3/0:0). Molecular biology experiments and molecular docking techniques verified that leonurine might improve hepatic lipid metabolism through the alpha-1A adrenergic receptor (ADRA1a)/AMPK/SCD1 axis. In summary, the present study explored the mechanism by which leonurine ameliorated NAFLD by inhibiting hepatic lipid synthesis via the ADRA1a/AMPK/SCD1 axis.

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来源期刊

International Journal of Molecular Sciences 化学-化学综合

自引率

10.70%

发文量

13472

审稿时长

1.7 months

期刊介绍： The International Journal of Molecular Sciences (ISSN 1422-0067) provides an advanced forum for chemistry, molecular physics (chemical physics and physical chemistry) and molecular biology. It publishes research articles, reviews, communications and short notes. Our aim is to encourage scientists to publish their theoretical and experimental results in as much detail as possible. Therefore, there is no restriction on the length of the papers or the number of electronics supplementary files. For articles with computational results, the full experimental details must be provided so that the results can be reproduced. Electronic files regarding the full details of the calculation and experimental procedure, if unable to be published in a normal way, can be deposited as supplementary material (including animated pictures, videos, interactive Excel sheets, software executables and others).