Liraglutide modulates gut microbiome and attenuates nonalcoholic fatty liver in db/db mice
Liraglutide modulates gut microbiome and attenuates nonalcoholic fatty liver in db/db mice
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DOI：
10.1016/j.lfs.2020.118457
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发表时间：
2020-11-15
期刊：
影响因子：
6.1
通讯作者：
Feng, Qin
中科院分区：
文献类型：
--
作者：
Liu, Qian;Cai, Bei-yu;Feng, Qin
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 524-7 group, and decreased the abundance of Klebsiella, Anaerotruncus, Bacteroides, Lachnospiraceae UCG-001, Lachnospiraceae NK4A136group, 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.
