Erythritol Improves Nonalcoholic Fatty Liver Disease by Activating Nrf2 Antioxidant Capacity
Erythritol Improves Nonalcoholic Fatty Liver Disease by Activating Nrf2 Antioxidant Capacity
复制标题
赤藓糖醇通过激活 Nrf2 抗氧化能力改善非酒精性脂肪肝
DOI：
10.1021/acs.jafc.1c05213
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发表时间：
2021-10-30
影响因子：
6.1
通讯作者：
Feng, Haihua
中科院分区：
文献类型：
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作者：
Jin, Meiyu;Wei, Yunfei;Feng, Haihua
非酒精性脂肪性肝病（NAFLD）是一种严重的脂肪疾病，已成为困扰人类社会的重要问题。因此，寻找安全有效的药物变得越来越重要。赤藓糖醇是一种具有多种生物功能的多元醇甜味剂。然而，Ery是否对NAFLD有缓解作用尚未见报道。因此，我们用油酸和棕榈酸作为HepG2细胞的体外模型。此外，我们选择tyloxapol高脂肪饮食的野生型小鼠和高脂肪饮食的核因子e2相关因子2 （Nrf2）敲除小鼠作为我们的体内模型。我们发现Ery可以逆转NAFLD模型引起的脂质积累、氧化应激和内质网应激。机制研究表明，Ery促进了Nrf2从细胞质向细胞核的易位，Ery与Nrf2的分子模拟对接结果显示它们之间存在氢键。此外，Ery可促进HO-1和NQO1抗氧化蛋白的产生，抑制内质网应激蛋白GPR78、p-PERK和CHOP的表达。相反，当Nrf2在小鼠中被敲除时，Ery失去了对NAFLD的保护作用。综上所述，我们发现Ery保护作用的潜在机制是通过激活Nrf2信号通路发挥抗氧化作用，从而抑制NAFLD内质网应激和脂质积累。
Nonalcoholic fatty liver disease (NAFLD) is a kind of serious fat disorder that has become a critical problem to human society. Therefore, finding drugs that are safe and effective has become more and more important. Erythritol (Ery) is a polyol sweetener with a variety of biological functions. However, whether Ery has a relieving effect on NAFLD has not been reported yet. Therefore, we induced HepG2 cells with oleic acid and palmitic acid as our in vitro model. Moreover, we choose wild-type mice with tyloxapol and high-fat diet and nuclear factor E2-related factor 2 (Nrf2) knockout mice with high-fat diet as our in vivo model. We found that Ery could reverse the lipid accumulation, oxidative stress, and endoplasmic reticulum stress caused by the NAFLD model. The mechanism studies showed that Ery promoted the translocation of Nrf2 from cytoplasm to nucleus, and the molecular simulation docking results of Ery and Nrf2 showed that there was a hydrogen bond between them. Moreover, Ery could promote the production of HO-1 and NQO1 antioxidant proteins and inhibit the expression of endoplasmic reticulum stress proteins GPR78, p-PERK, and CHOP. On the contrast, when Nrf2 was knocked out in mice, Ery lost its protective effect on NAFLD. In conclusion, we found that the potential mechanism of Ery's protective effect is that it plays an antioxidant role by activating the Nrf2 signaling pathway, thereby inhibiting endoplasmic reticulum stress and lipid accumulation in NAFLD.