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丁香酚通过涉及胰高血糖素样肽-1 的肠-脑-肝轴缓解大鼠非酒精性脂肪性肝病。

Eugenol alleviated nonalcoholic fatty liver disease in rat via a gut-brain-liver axis involving glucagon-like Peptide-1.

机构信息

Department of Pharmacy, College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao, China.

Shandong Xinhua Pharmaceutical Company Limited, Zibo, China.

出版信息

Arch Biochem Biophys. 2022 Aug 15;725:109269. doi: 10.1016/j.abb.2022.109269. Epub 2022 May 1.

DOI:10.1016/j.abb.2022.109269
PMID:35508252
Abstract

Eugenol, an active ingredient of many medicinal aromatic plants, has been proved to have the hypolipidemic effect, but its potential mechanism of action is still unknown. This study aimed to investigate whether eugenol regulates liver lipid accumulation in high-fat diet (HFD) induced nonalcoholic fatty liver disease (NAFLD) rats via the gut-brain-liver axis involving glucagon-like peptide-1 (GLP-1). Hepatic vagotomy was performed in NAFLD rats to determine the role of eugenol in regulating hepatic lipid accumulation via vagus nerve. The results showed that after eight weeks of eugenol administration in NAFLD rats, serum total cholesterol (TC), triglyceride (TG) and hepatic TG decreased. However, eugenol showed no significant effect on the increased food intakes and weight gain caused by the HFD. Eugenol promoted the secretion of GLP-1 into the blood, increased GLP-1 receptor (GLP-1R) expression in the duodenum, liver, arcuate nucleus (ARC) and paraventricular nucleus (PVN), increased c-fos expression in the nucleus tractus solitarii (NTS), and promoted ZO-1 and occludin expression in duodenum. Furthermore, steatosis and lipid accumulation were significantly alleviated. Hepatic vagotomy partially attenuated the improvement of eugenol in hepatic lipid accumulation in NAFLD rats. In conclusion, eugenol regulates hepatic lipid metabolism via a gut-brain-liver axis involving in GLP-1, providing a new strategy for the treatment of NAFLD.

摘要

丁香酚是许多药用芳香植物的活性成分,已被证明具有降血脂作用,但作用机制尚不清楚。本研究旨在探讨丁香酚是否通过涉及胰高血糖素样肽-1 (GLP-1) 的肠-脑-肝轴调节高脂饮食 (HFD) 诱导的非酒精性脂肪性肝病 (NAFLD) 大鼠肝脏脂质积聚。在 NAFLD 大鼠中进行肝迷走神经切断术,以确定丁香酚通过迷走神经调节肝脏脂质积聚的作用。结果表明,在 NAFLD 大鼠给予丁香酚 8 周后,血清总胆固醇 (TC)、甘油三酯 (TG) 和肝 TG 降低。然而,丁香酚对 HFD 引起的食物摄入量增加和体重增加没有显著影响。丁香酚促进 GLP-1 分泌到血液中,增加十二指肠、肝脏、弓状核 (ARC) 和室旁核 (PVN) 中的 GLP-1 受体 (GLP-1R) 表达,增加孤束核 (NTS) 中的 c-fos 表达,并促进十二指肠中 ZO-1 和闭合蛋白的表达。此外,脂肪变性和脂质积聚得到明显缓解。肝迷走神经切断术部分减弱了丁香酚对 NAFLD 大鼠肝脏脂质积聚的改善作用。总之,丁香酚通过涉及 GLP-1 的肠-脑-肝轴调节肝脏脂质代谢,为治疗 NAFLD 提供了新策略。

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