Liraglutide modulates gut microbiome and attenuates nonalcoholic fatty liver in db/db mice

Liu, Qian; Cai, Bei-yu; Zhu, Lixin; Xin, Xin; Wang, Xin; An, Zhenmei; Li, Shuang; Hu, Yiyang; Feng, Qin

doi:10.1016/j.lfs.2020.118457

Cited by 62 publications

(45 citation statements)

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“…Interestingly, the Romboutisa ASV_585 negatively correlated with both LSM and CAP measurements. We found only one reference linking the Romboutsia genus with liver complications in mice 42 . In this study, a glucagon-like peptide-1 analog (liraglutide) improved fatty liver in db/db mice and this was associated with an enrichment of Romboutsia genus in the colon content.…”

Section: Discussionmentioning

confidence: 99%

Microbiota analysis and transient elastography reveal new extra-hepatic components of liver steatosis and fibrosis in obese patients

Lanthier

Rodriguez

Nachit

et al. 2021

Sci Rep

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Obesity could lead to metabolic dysfunction-associated fatty liver disease (MAFLD), which severity could be linked to muscle and gut microbiota disturbances. Our prospective study enrolled 52 obese patients whose MAFLD severity was estimated by transient elastography. Patients with severe steatosis (n = 36) had higher ALAT values, fasting blood glucose levels as well as higher visceral adipose tissue area and skeletal muscle index evaluated by computed tomography. Patients with fibrosis (n = 13) had higher ASAT values, increased whole muscle area and lower skeletal muscle density index. In a multivariate logistic regression analysis, myosteatosis was the strongest factor associated with fibrosis. Illumina sequencing of 16S rRNA gene amplicon was performed on fecal samples. The relative abundance of fecal Clostridium sensu stricto was significantly decreased with the presence of liver fibrosis and was negatively associated with liver stiffness measurement and myosteatosis. In addition, 19 amplicon sequence variants were regulated according to the severity of the disease. Linear discriminant analysis effect size (LEfSe) also highlighted discriminant microbes in patients with fibrosis, such as an enrichment of Enterobacteriaceae and Escherichia/Shigella compared to patients with severe steatosis without fibrosis. All those data suggest a gut-liver-muscle axis in the pathogenesis of MAFLD complications.

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Section: Discussionmentioning

confidence: 99%

Microbiota analysis and transient elastography reveal new extra-hepatic components of liver steatosis and fibrosis in obese patients

Lanthier

Rodriguez

Nachit

et al. 2021

Sci Rep

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“…When liver tissue is diseased or liver cells are damaged, the activity of related liver enzymes and serum concentrations, such as AKP, ALT and AST, is increased ( Zhou et al, 2017 ; Eshraghian et al, 2020 ; Choudhary et al, 2021 ; Nielsen et al, 2021 ). NAFL itself is also a metabolic disease that may be manifested by abnormal lipid metabolism and a significant or insignificant increase in blood lipids, such as HDLC, LDL-C, TC and TG ( Jimenez-Rivera et al, 2017 ; Chen et al, 2020 ; Liu et al, 2020 ; Mohammadi et al, 2020 ). In our study, serum HDL-C in model mice increased and decreased after administration, which was similar to the results of Sheng et al ( Sheng et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Revealing the Mechanism of Huazhi Rougan Granule in the Treatment of Nonalcoholic Fatty Liver Through Intestinal Flora Based on 16S rRNA, Metagenomic Sequencing and Network Pharmacology

et al. 2022

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Background: The incidence of Nonalcoholic Fatty Liver (NAFL) is increasing year by year, growing evidence suggests that the intestinal flora plays a causative role in NAFL. Huazhi Rougan Granule (HRG) is commonly used in the clinical treatment of NAFL. It is reported that it can reduce lipids and protect the liver, but no research has confirmed whether the drug’s effect is related to the intestinal flora. Therefore, we investigated whether the effect of HRG is related to the regulation of intestinal flora to further explore the mechanism of HRG in the treatment of NAFL through intestinal flora.Methods: In this study, C57BL/6J mice were fed a high-fat diet for 8 weeks, and the high-fat diet plus HRG or polyene phosphatidylcholine capsules were each administered by gavage for 4 weeks. High-throughput sequencing, network pharmacology, and molecular docking were used to explore the mechanism of HRG in the treatment of NAFL through intestinal flora.Results: HRG treatment can reduce body weight gain, lipid accumulation in liver and lipogenesis and reduce serum biochemical indexes in high-fat-fed mice. Analysis of intestinal flora showed that HRG changed the composition of intestinal flora, which was characterized by a decrease in the Firmicutes/Bacteroidetes ratio. Moreover, the species distribution was significantly correlated with AKP, HDL-C, and TG. Metagenetic analysis showed that HRG altered the functional composition and functional diversity of microorganisms, which was mainly characterized by an increase in the abundance of metabolic pathways. The network pharmacology results show that the mechanism of HRG in the treatment of NAFL through intestinal flora is mainly reflected in the biological process of gene function and related to infectious diseases, immune systems, and signal transduction pathways, such as cytokine-cytokine receptor interaction, Chagas disease, IL-17 signaling pathway and other signaling pathways.Conclusion: These results strongly suggest that HRG may alleviate NAFL by preventing IFD.

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“…Referring to the existing literature, these changes might be linked to weight loss. 49,50 As our results showed, Actinobacteria were significantly positively associated with body weight, liver weight and metabolic parameters in T2DM, while Bacteroidetes displayed a negative cor-Fig. 9 The proposed mechanism of SG1 to alleviate T2DM.…”

Section: Papermentioning

confidence: 70%

Sesquiterpene glycoside isolated from loquat leaf targets gut microbiota to prevent type 2 diabetes mellitus in db/db mice

Zhou

Chen

et al. 2022

Food Funct.

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Liraglutide modulates gut microbiome and attenuates nonalcoholic fatty liver in db/db mice

Cited by 62 publications

References 50 publications

Microbiota analysis and transient elastography reveal new extra-hepatic components of liver steatosis and fibrosis in obese patients

Microbiota analysis and transient elastography reveal new extra-hepatic components of liver steatosis and fibrosis in obese patients

Revealing the Mechanism of Huazhi Rougan Granule in the Treatment of Nonalcoholic Fatty Liver Through Intestinal Flora Based on 16S rRNA, Metagenomic Sequencing and Network Pharmacology

Sesquiterpene glycoside isolated from loquat leaf targets gut microbiota to prevent type 2 diabetes mellitus in db/db mice

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