Aims

Liraglutide, a glucagon-like peptide-1(GLP-1) analog, is effective for the treatment of type II diabetes and nonalcoholic fatty liver disease (NAFLD). It was proved that gut microbiome plays a role in the development of NAFLD. This study aims to observe the therapeutic effect of liraglutide on nonalcoholic fatty liver (NAFL) in mice and effect on the gut microbial community.

Main methods

The db/db mice were used as the NAFL model, and lactulose was used as the positive control drug. Hepatic triglyceride, liver histopathology, and indices of glucolipid metabolism, including fasting blood glucose, fasting insulin, insulin resistance index and blood lipids were evaluated after treatment of liraglutide or lactulose for four weeks. The colonic microbiome of the mice was analyzed by 16S rRNA gene sequencing.

Key findings

Liraglutide significantly reduced the hepatic triglyceride (TG) content, alanine aminotransferase (ALT) activity, fasting blood glucose, insulin resistance and serum low density lipoprotein (LDL) in the db/db mice. In terms of hepatic pathologies, hepatic steatosis was significantly improved after liraglutide treating. Microbiome analysis revealed that liraglutide significantly increased the abundance of Akkermansia, Romboutsia, norank_f_Bacteroidales_S24-7_group, and decreased the abundance of Klebsiella, Anaerotruncus, Bacteroides, Lachnospiraceae_UCG-001, Lachnospiraceae_NK4A136_group, Ruminiclostridium, uncultured_f__Ruminococcaceae, and Desulfovibrio.

Significance

The results of the present study suggested that liraglutide had a certain therapeutic effect on fatty liver in db/db mice and had an impact on the composition of the intestinal microflora, especially some bacteria related to glucolipid metabolism and intestinal inflammation. Affecting gut microbiome might be a potential mechanism of liraglutide in treating NAFL.

中文翻译：

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利拉鲁肽可调节db / db小鼠的肠道微生物组并减弱非酒精性脂肪肝。

目的

利拉鲁肽是一种胰高血糖素样肽1（GLP-1）类似物，可有效治疗II型糖尿病和非酒精性脂肪性肝病（NAFLD）。事实证明，肠道微生物组在NAFLD的发生中起作用。这项研究旨在观察利拉鲁肽对小鼠非酒精性脂肪肝（NAFL）的治疗作用以及对肠道微生物群落的影响。

主要方法

db / db小鼠用作NAFL模型，乳果糖用作阳性对照药物。在利拉鲁肽或乳果糖治疗四个星期后，评估了肝甘油三酸酯，肝组织病理学和糖脂代谢指标，包括空腹血糖，空腹胰岛素，胰岛素抵抗指数和血脂。通过16S rRNA基因测序分析小鼠的结肠微生物组。

主要发现

利拉鲁肽显着降低db / db小鼠的肝甘油三酸酯（TG）含量，丙氨酸氨基转移酶（ALT）活性，空腹血糖，胰岛素抵抗和血清低密度脂蛋白（LDL）。就肝病理而言，利拉鲁肽治疗后肝脂肪变性明显改善。微生物分析显示，利拉鲁肽显著上升的丰度Akkermansia，Romboutsia，norank_f_Bacteroidales_S24-7_group，降低丰克雷伯氏菌，Anaerotruncus，杆菌，Lachnospiraceae_UCG-001，Lachnospiraceae_NK4A136_group，Ruminiclostridium，uncultured_f__Ruminococcaceae和Desulfovibrio。

意义

本研究结果表明利拉鲁肽对db / db小鼠的脂肪肝具有一定的治疗作用，并且对肠道菌群的组成有影响，特别是与糖脂代谢和肠道炎症有关的某些细菌。影响肠道微生物组可能是利拉鲁肽治疗NAFL的潜在机制。