School of Public Health, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, PR. China.
College of Animal Science, Zhejiang University, Hangzhou, Zhejiang, PR. China.
Food Funct. 2022 Mar 21;13(6):3368-3380. doi: 10.1039/d1fo03952k.
-Acetylcysteine (NAC), a well-accepted antioxidant, has been shown to protect against high fat diet (HFD)-induced obesity-associated non-alcoholic fatty liver disease (NAFLD) in mice. However, the underlying mechanism(s) of the beneficial role of NAC is still not fully understood. Our study aimed to evaluate the protective effect of NAC against NAFLD in terms of gut microbiota homeostasis. Thirty-two C57BL/6 mice were divided into four groups, including chow diet (CHOW), high-fat diet (HFD), CHOW + NAC (2 g L in the drinking water), and HFD + NAC groups, and fed for 12 weeks. NAC supplementation significantly improved HFD-induced obesity, dyslipidemia, and liver dysfunction in mice. NAC also rescued HFD-caused disorder of the gut microbiota. Intriguingly, removing intestinal microorganisms by antibiotics (ABX) obviously abolished NAC supplementation-rescued hepatic steatosis and liver injury, indicating the involvement of the gut microbiota in the beneficial role of NAC. The profiles of 1145 expressed hepatic mRNAs were analyzed by whole transcriptome sequencing. Among those, 5 up-expressed mRNAs induced by a HFD, including , , , , and , were reversed by NAC treatment, which was further verified by a quantitative real-time polymerase chain reaction (qRT-PCR). Meanwhile, those 5 mRNAs exhibited a significant (negative or positive) association with bacterial phyla or genera, including phyla and and genera and , by Spearman's correlation analysis. These results suggested that the homeostasis of the gut microbiota plays an important role in NAC-improved NAFLD by affecting the enterohepatic axis.
乙酰半胱氨酸（NAC）作为一种公认的抗氧化剂，已被证明可预防高脂肪饮食（HFD）诱导的肥胖相关非酒精性脂肪性肝病（NAFLD）。然而，NAC 有益作用的潜在机制仍不完全清楚。我们的研究旨在评估 NAC 在肠道微生物组平衡方面对 NAFLD 的保护作用。将 32 只 C57BL/6 小鼠分为 4 组，包括普通饮食（CHOW）、高脂肪饮食（HFD）、CHOW+NAC（2 g L 在饮水中）和 HFD+NAC 组，喂养 12 周。NAC 补充显著改善了 HFD 诱导的肥胖、血脂异常和肝功能障碍。NAC 还挽救了 HFD 引起的肠道微生物群紊乱。有趣的是，用抗生素（ABX）去除肠道微生物明显消除了 NAC 补充对肝脂肪变性和肝损伤的挽救作用，表明肠道微生物群参与了 NAC 的有益作用。通过全转录组测序分析了 1145 个表达的肝 mRNA 谱。其中，5 个由 HFD 诱导的上调 mRNA，包括、、、和，被 NAC 处理逆转，这通过定量实时聚合酶链反应（qRT-PCR）进一步验证。同时，通过 Spearman 相关分析，这些 5 个 mRNA 与细菌门或属呈显著（负相关或正相关）相关，包括门和和属和。这些结果表明，肠道微生物组的平衡通过影响肠肝轴在 NAC 改善 NAFLD 中起着重要作用。
