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圣草次苷通过激活线粒体生物合成改善饮食诱导的肝脂肪变性。

Eriocitrin ameliorates diet-induced hepatic steatosis with activation of mitochondrial biogenesis.

作者信息

Hiramitsu Masanori, Shimada Yasuhito, Kuroyanagi Junya, Inoue Takashi, Katagiri Takao, Zang Liqing, Nishimura Yuhei, Nishimura Norihiro, Tanaka Toshio

机构信息

1] Department of Molecular and Cellular Pharmacology, Pharmacogenomics and Pharmacoinformatics, Mie University Graduate School of Medicine, Mie, Japan [2] Central Laboratory, Pokka Sapporo Food & Beverage Ltd., Aichi, Japan [3].

1] Department of Molecular and Cellular Pharmacology, Pharmacogenomics and Pharmacoinformatics, Mie University Graduate School of Medicine, Mie, Japan [2] Mie University Medical Zebrafish Research Center, Mie, Japan [3] Department of Systems Pharmacology, Mie University Graduate School of Medicine, Mie, Japan [4] Department of Bioinformatics, Mie University Life Science Research Center, Mie, Japan [5] Department of Omics Medicine, Mie University Industrial Technology Innovation Institute, Mie, Japan [6].

出版信息

Sci Rep. 2014 Jan 15;4:3708. doi: 10.1038/srep03708.

Abstract

Lemon (Citrus limon) contains various bioactive flavonoids, and prevents obesity and obesity-associated metabolic diseases. We focused on eriocitrin (eriodictyol 7-rutinoside), a powerful antioxidative flavonoid in lemon with lipid-lowering effects in a rat model of high-fat diet. To investigate the mechanism of action of eriocitrin, we conducted feeding experiments on zebrafish with diet-induced obesity. Oral administration of eriocitrin (32 mg/kg/day for 28 days) improved dyslipidaemia and decreased lipid droplets in the liver. DNA microarray analysis revealed that eriocitrin increased mRNA of mitochondrial biogenesis genes, such as mitochondria transcription factor, nuclear respiratory factor 1, cytochrome c oxidase subunit 4, and ATP synthase. In HepG2 cells, eriocitrin also induced the corresponding orthologues, and reduced lipid accumulation under conditions of lipid loading. Eriocitrin increased mitochondrial size and mtDNA content, which resulted in ATP production in HepG2 cells and zebrafish. In summary, dietary eriocitrin ameliorates diet-induced hepatic steatosis with activation of mitochondrial biogenesis.

摘要

柠檬(Citrus limon)含有多种生物活性黄酮类化合物,可预防肥胖及肥胖相关的代谢性疾病。我们重点研究了圣草次苷(圣草酚7-芸香糖苷),它是柠檬中一种具有强大抗氧化作用的黄酮类化合物,在高脂饮食大鼠模型中具有降血脂作用。为了研究圣草次苷的作用机制,我们对饮食诱导肥胖的斑马鱼进行了喂养实验。口服圣草次苷(32毫克/千克/天,持续28天)改善了血脂异常,并减少了肝脏中的脂滴。DNA微阵列分析显示,圣草次苷增加了线粒体生物发生基因的mRNA水平,如线粒体转录因子、核呼吸因子1、细胞色素c氧化酶亚基4和ATP合酶。在HepG2细胞中,圣草次苷也诱导了相应的同源物,并在脂质加载条件下减少了脂质积累。圣草次苷增加了线粒体大小和线粒体DNA含量,从而导致HepG2细胞和斑马鱼中ATP的产生。总之,饮食中的圣草次苷通过激活线粒体生物发生改善了饮食诱导的肝脂肪变性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0177/3892443/11ed11784802/srep03708-f1.jpg

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