Amendment history : Corrigendum ( April 2009 ) Adenosine signaling contributes to ethanol-induced fatty liver in mice
Amendment history : Corrigendum ( April 2009 ) Adenosine signaling contributes to ethanol-induced fatty liver in mice
复制标题
DOI：
--
复制
发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Zhongsheng Peng;P. Borea;T. Wilder;H. Yee;L. Chiriboga;M. Blackburn;G. Azzena;G. Resta;B. Cronstein
中科院分区：
文献类型：
--
作者：
Zhongsheng Peng;P. Borea;T. Wilder;H. Yee;L. Chiriboga;M. Blackburn;G. Azzena;G. Resta;B. Cronstein
脂肪肝通常与酒精摄入和滥用有关。虽然这些脂肪变化的分子发病机制已被充分了解，但乙醇刺激这些分子变化的生化和药理学机制仍然未知。在乙醇代谢过程中，腺苷由 5′ 核苷酸酶产生，已知腺苷的产生和腺苷受体的激活在肝纤维化的发展中发挥关键作用。因此，我们研究了腺苷及其受体是否在酒精诱导的脂肪肝的发展中发挥作用。以 Lieber-DeCarli 饮食喂养乙醇的 WT 小鼠出现了肝脏脂肪变性，包括肝脏甘油三酯含量增加，而缺乏 5′-核苷酸酶或腺苷 A1 或 A2B 受体的小鼠则免受脂肪肝的影响。在用腺苷 A1 或 A2B 受体拮抗剂治疗的 WT 小鼠中也观察到类似的保护作用。脂肪肝表现出参与脂肪酸合成的基因表达增加（通过阻断腺苷 A1 受体来阻止），以及参与脂肪酸代谢的基因表达减少（通过阻断腺苷 A2B 受体来阻止）。体外研究支持腺苷 A1 受体在促进脂肪酸合成和 A2B 受体中的作用 [...] 研究文章 胃肠病学
Fatty liver is commonly associated with alcohol ingestion and abuse. While the molecular pathogenesis of these fatty changes is well understood, the biochemical and pharmacological mechanisms by which ethanol stimulates these molecular changes remain unknown. During ethanol metabolism, adenosine is generated by the enzyme ecto-5¢nucleotidase, and adenosine production and adenosine receptor activation are known to play critical roles in the development of hepatic fibrosis. We therefore investigated whether adenosine and its receptors play a role in the development of alcohol-induced fatty liver. WT mice fed ethanol on the Lieber-DeCarli diet developed hepatic steatosis, including increased hepatic triglyceride content, while mice lacking ecto-5¢-nucleotidase or adenosine A1 or A2B receptors were protected from developing fatty liver. Similar protection was also seen in WT mice treated with either an adenosine A1 or A2B receptor antagonist. Steatotic livers demonstrated increased expression of genes involved in fatty acid synthesis, which was prevented by blockade of adenosine A1 receptors, and decreased expression of genes involved in fatty acid metabolism, which was prevented by blockade of adenosine A2B receptors. In vitro studies supported roles for adenosine A1 receptors in promoting fatty acid synthesis and for A2B receptors [...] Research Article Gastroenterology