Introduction: Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases. The development of NAFLD is closely associated with hepatic lipotoxicity, inflammation, and oxidative stress. The new concept of NAFLD treatment is to seek molecular control of lipid metabolism and hepatic redox hemostasis. Phoenixin is a newly identified neuropeptide with pleiotropic effects. This study investigated the effects of phoenixin 14 against high-fat diet (HFD)-induced NAFLD in mice.
Materials and Methods: For this study, we used HFD-induced NAFLD mice models to analyze the effect of phonenixin14. The mice were fed on HFD and normal diet and also given phoenixin 14 (100 ng/g body weight) by gastrogavage for 10 weeks. The peripheral blood samples were collected for biochemical assays. The liver tissues were examined for HFD-induced tissue fibrosis, lipid deposition and oxidative activity including SOD, GSH, and MDA. The liver tissues were analyzed for the inflammatory cytokines and oxidative stress pathway genes.
Results: The results indicate that phoenixin 14 significantly ameliorated HFD-induced obesity and fatty liver. The biochemical analysis of blood samples revealed that phoenixin 14 ameliorated HFD-induced elevated circulating alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol, and triglyceride levels, suggesting that phoenixin 14 has a protective role in liver function and lipid metabolism. Hematoxylin-eosin (HE) and Oil Red O staining of the liver showed that phoenixin 14 alleviated HFD-induced tissue damage and lipid deposition in the liver. Furthermore, the mice administered with phoenixin 14 had increased hepatic SOD activity, increased production of GSH and reduced MDA activity, as well as reduced production of TNF-α and IL-6 suggesting that phoenixin 14 exerts beneficial effects against inflammation and ROS. The findings suggest an explanation of how mechanistically phoenixin 14 ameliorated HFD-induced reduced activation of the SIRT1/AMPK and NRF2/HO-1 pathways.
Conclusion: Collectively, this study revealed that phoenixin 14 exerts a protective effect in experimental NAFLD mice. Phoenixin could be of the interest in preventive modulation of NAFLD.

Keywords: phoenixin 14, nonalcoholic fatty liver disease, NAFLD, oxidative stress, inflammation, NRF2/HO-1, SIRT1/AMPK


中文翻译：

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Phoenixin 14 在实验小鼠中抑制高脂饮食诱导的非酒精性脂肪肝疾病

简介：非酒精性脂肪性肝病（NAFLD）是最常见的慢性肝病之一。NAFLD 的发生与肝脂毒性、炎症和氧化应激密切相关。NAFLD治疗的新理念是寻求脂质代谢的分子控制和肝脏氧化还原止血。Phoenixin 是一种新发现的具有多效性的神经肽。本研究调查了phoenixin 14 对小鼠高脂饮食（HFD）诱导的NAFLD 的影响。
材料和方法：在这项研究中，我们使用 HFD 诱导的 NAFLD 小鼠模型来分析 phonenixin14 的作用。以HFD和正常饮食喂养小鼠，并通过胃灌胃给予phoenixin 14（100 ng / g体重）10周。收集外周血样品用于生化测定。检查肝组织的 HFD 诱导的组织纤维化、脂质沉积和氧化活性，包括 SOD、GSH 和 MDA。分析肝组织的炎性细胞因子和氧化应激途径基因。
结果：结果表明，phoenixin 14 显着改善了 HFD 诱导的肥胖和脂肪肝。血液样本的生化分析显示，phoenixin 14 可改善 HFD 引起的循环丙氨酸氨基转移酶 (ALT)、天冬氨酸氨基转移酶 (AST)、总胆固醇和甘油三酯水平升高，表明 phoenixin 14 在肝功能和脂质代谢中具有保护作用。肝脏的苏木精-伊红 (HE) 和油红 O 染色表明，phoenixin 14 减轻了 HFD 诱导的肝脏组织损伤和脂质沉积。此外，给予phoenixin 14的小鼠肝脏SOD活性增加，GSH产生增加，MDA活性降低，TNF-α和IL-6产生减少，这表明phoenixin 14对炎症和活性氧发挥有益作用。
结论：总的来说，本研究表明，phoenixin 14 对实验性 NAFLD 小鼠具有保护作用。Phoenixin 可能对 NAFLD 的预防性调节感兴趣。

关键词： phoenixin 14，非酒精性脂肪肝，NAFLD，氧化应激，炎症，NRF2/HO-1，SIRT1/AMPK