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Dietary supplementation with myo-inositol reduces high-fructose diet-induced hepatic ChREBP binding and acetylation of histones H3 and H4 on the Elovl6 gene in rats
Nutrition Research ( IF 4.5 ) Pub Date : 2020-12-25 , DOI: 10.1016/j.nutres.2020.12.022
Mayu Hibi 1 , Tomoyuki Nakagawa 2 , Takashi Hayakawa 2 , Emiko Yanase 2 , Masaya Shimada 2
Affiliation  

ELOVL fatty acid elongase 6 (ELOVL6) is a long-chain fatty acid elongase, and the hepatic expression of the Elovl6 gene and accumulation of triglycerides (TG) are enhanced by long-term high-fructose intake. Fatty acid synthesis genes, including Elovl6, are regulated by lipogenic transcription factors, sterol regulatory element-binding protein 1c (SREBP-1c) and carbohydrate-responsive element-binding protein (ChREBP). In addition, carbohydrate signals induce the expression of fatty acid synthase not only via these transcription factors but also via histone acetylation. Since a major lipotrope, myo-inositol (MI), can repress short-term high-fructose-induced fatty liver and the expression of fatty acid synthesis genes, we hypothesized that MI might influence SREBP-1c, ChREBP, and histone acetylation of Elovl6 in fatty liver induced by even short-term high-fructose intake. This study aimed to investigate whether dietary supplementation with MI affects Elovl6 expression, SREBP-1 and ChREBP binding, and acetylation of histones H3 and H4 at the Elovl6 promoter in short-term high-fructose diet-induced fatty liver in rats. Rats were fed a control diet, high-fructose diet, or high-fructose diet supplemented with 0.5% MI for 10 days. This study showed that MI supplementation reduced short-term high-fructose diet-induced hepatic expression of the Elovl6 gene, ChREBP binding, but not SREBP-1 binding, and acetylation of histones H3 and H4 at the Elovl6 promoter.



中文翻译:

膳食补充肌醇可降低高果糖饮食诱导的大鼠肝脏 ChREBP 结合和组蛋白 H3 和 H4 乙酰化 Elovl6 基因

ELOVL 脂肪酸延长酶 6 (ELOVL6) 是一种长链脂肪酸延长酶,长期高果糖摄入会增强Elovl6基因的肝脏表达和甘油三酯 (TG) 的积累。脂肪酸合成基因,包括Elovl6、受脂肪生成转录因子、甾醇调节元件结合蛋白 1c (SREBP-1c) 和碳水化合物反应元件结合蛋白 (ChREBP) 的调节。此外,碳水化合物信号不仅通过这些转录因子而且通过组蛋白乙酰化诱导脂肪酸合酶的表达。由于主要的促脂剂肌醇 (MI) 可以抑制短期高果糖诱导的脂肪肝和脂肪酸合成基因的表达,我们假设 MI 可能影响 SREBP-1c、ChREBP 和Elovl6 的组蛋白乙酰化在即使是短期高果糖摄入引起的脂肪肝中。本研究旨在调查膳食补充剂 MI 是否影响Elovl6在短期高果糖饮食诱导的大鼠脂肪肝中,SREBP-1 和 ChREBP 的表达、SREBP-1 和 ChREBP 结合以及Elovl6启动子处组蛋白 H3 和 H4 的乙酰化。给大鼠喂食对照饮食、高果糖饮食或补充有 0.5% MI 的高果糖饮食 10 天。该研究表明,MI 补充剂降低了短期高果糖饮食诱导的Elovl6基因肝脏表达、ChREBP 结合,但不降低 SREBP-1 结合,以及Elovl6启动子处组蛋白 H3 和 H4 的乙酰化。

更新日期:2020-12-25
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