Shuguang Hospital Affliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203,China; Baoshan District Hospital of Integrated Traditional Chinese Medicine of Shanghai, Shanghai 201900, China.
Shuguang Hospital Affliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203,China.
Life Sci. 2020 Nov 15;261:118457. doi: 10.1016/j.lfs.2020.118457. Epub 2020 Sep 19.
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.
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.
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.
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.
利拉鲁肽是一种胰高血糖素样肽-1（GLP-1）类似物，对 2 型糖尿病和非酒精性脂肪性肝病（NAFLD）的治疗有效。现已证实肠道微生物群在 NAFLD 的发生发展中发挥作用。本研究旨在观察利拉鲁肽对 db/db 小鼠非酒精性脂肪肝（NAFL）的治疗作用及其对肠道微生物群落的影响。
采用 db/db 小鼠作为 NAFL 模型，乳果糖作为阳性对照药物。治疗 4 周后，评估利拉鲁肽或乳果糖治疗后肝组织甘油三酯（TG）含量、肝组织病理学变化以及糖脂代谢相关指标，包括空腹血糖、空腹胰岛素、胰岛素抵抗指数和血脂。采用 16S rRNA 基因测序分析小鼠结肠微生物组。
利拉鲁肽可显著降低 db/db 小鼠肝组织 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）。在肝组织病理学方面，利拉鲁肽治疗后肝脂肪变性明显改善。微生物组分析显示，利拉鲁肽可显著增加 Akkermansia、Romboutsia、norank_f_Bacteroidales_S24-7_group 的丰度，降低 Klebsiella、Anaerotruncus、Bacteroides、Lachnospiraceae_UCG-001、Lachnospiraceae_NK4A136_group、Ruminiclostridium、uncultured_f__Ruminococcaceae 和 Desulfovibrio 的丰度。
本研究结果表明，利拉鲁肽对 db/db 小鼠脂肪肝具有一定的治疗作用，并对肠道微生物群落组成产生影响，特别是一些与糖脂代谢和肠道炎症相关的细菌。影响肠道微生物群可能是利拉鲁肽治疗 NAFL 的潜在机制。
