Serine prevented high-fat diet-induced oxidative stress by activating AMPK and epigenetically modulating the expression of glutathione synthesis-related genes
Serine prevented high-fat diet-induced oxidative stress by activating AMPK and epigenetically modulating the expression of glutathione synthesis-related genes
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丝氨酸通过激活 AMPK 和表观遗传调节谷胱甘肽合成相关基因的表达来预防高脂饮食诱导的氧化应激
DOI：
10.1016/j.bbadis.2017.11.009
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发表时间：
2018-02-01
影响因子：
6.2
通讯作者：
Yin, Yulong
中科院分区：
文献类型：
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作者：
Zhou, Xihong;He, Liuqin;Yin, Yulong
在非酒精性脂肪性肝病（NAELD）患者中观察到丝氨酸缺乏。补充丝氨酸是否对预防NAFLD有任何有益的影响仍然未知。本研究旨在探讨补充丝氨酸对肝脏氧化应激和脂肪变性的影响及其相关机制。将40只雄性C57 BL/6 J小鼠（9周龄）随机分为四组（n = 10），分别饲喂：i）低脂饮食; ii）补充有1%（wt：vol）丝氨酸的低脂饮食; iii）高脂（HF）饮食;和iv）补充有1%丝氨酸的HF饮食。棕榈酸（PA）处理的原代肝细胞分离成年小鼠也被用来研究丝氨酸对氧化应激的影响。结果表明，丝氨酸补充增加葡萄糖耐量和胰岛素敏感性，并保护小鼠免受肝脏脂质积累，但没有显着降低HF饮食诱导的体重增加。此外，丝氨酸补充保护谷胱甘肽（GSH）抗氧化系统，并防止谷胱甘肽合成相关基因启动子的超甲基化，同时减少HF饮食小鼠的活性氧（ROS）。此外，我们发现，丝氨酸补充增加磷酸化和S-谷胱甘肽的AMP激活的蛋白激酶a亚基（AMPK α），并降低活性氧，丙二醛和甘油三酯含量在PA处理的原代肝细胞。然而，虽然AMPK活性或GSH合成被抑制，丝氨酸对PA处理的原代肝细胞的上述影响没有观察到。我们的研究结果表明，丝氨酸补充剂可以通过表观遗传学调节谷胱甘肽合成相关基因的表达和通过AMPK激活来预防HF饮食诱导的氧化应激和脂肪变性。
Serine deficiency has been observed in patients with nonalcoholic fatty liver disease (NAELD). Whether serine supplementation has any beneficial effects on the prevention of NAFLD remains unknown. The present study was conducted to investigate the effects of serine supplementation on hepatic oxidative stress and steatosis and its related mechanisms. Forty male C57BL/6J mice (9 week-old) were randomly assigned into four groups (n = 10) and fed: i) a low-fat diet; ii) a low-fat diet supplemented with 1% (wt:vol) serine; iii) a high-fat (HF) diet; and iv) a HF diet supplemented with 1% serine, respectively. Palmitic acid (PA)-treated primary hepatocytes separated from adult mice were also used to study the effects of serine on oxidative stress. The results showed that serine supplementation increased glucose tolerance and insulin sensitivity, and protected mice from hepatic lipid accumulation, but did not significantly decreased HF diet-induced weight gain. In addition, serine supplementation protected glutathione (GSH) antioxidant system and prevented hypermethylation in the promoters of glutathione synthesis-related genes, while decreasing reactive oxygen species (ROS) in mice fed a HF diet. Moreover, we found that serine supplementation increased phosphorylation and S-glutathionylation of AMP-activated protein kinase a subunit (AMPK alpha), and decreased ROS, malondialdehyde and triglyceride contents in PA-treated primary hepatocytes. However, while AMPK activity or GSH synthesis was inhibited, the above-mentioned effects of serine on PA-treated primary hepatocytes were not observed. Our results suggest that serine supplementation could prevent HF diet-induced oxidative stress and steatosis by epigenetically modulating the expression of glutathione synthesis-related genes and through AMPK activation.