Characteristics of intestinal microbiota in C57BL/6 mice with non-alcoholic fatty liver induced by high-fat diet

Yan, Guangwen; Li, Shuaibing; Wen, Yuhang; Luo, Yadan; Huang, Jing-Rong; Chen, Baoting; Lv, Shuya; Chen, Lang; He, Lvqin; He, Manli; Yang, Qian; Yu, Zehui; Xiao, Wudian; Tang, Yong; Li, Weiyao; Han, Jianhong; Zhao, Fangfang; Yu, Shumin; Kong, Fanzuo; Abbasi, Benazir; Yin, Heng; Gu, Congwei

doi:10.3389/fmicb.2022.1051200

Cited by 3 publications

(2 citation statements)

References 57 publications

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“…Due to sex differences in susceptibility to NAFLD, only male mice were used in HFD‐induced NAFLD models (Yan et al, 2022). In this study, we established an animal model of NAFLD in male mice through the HFD diet and found that the body weight was increased, but the obesity and liver weight of mice were relieved after LQ treatment.…”

Section: Discussionmentioning

confidence: 99%

Liquiritigenin regulates insulin sensitivity and ameliorates inflammatory responses in the nonalcoholic fatty liver by activation PI3K/AKT pathway

Bao¹,

Hao

Jiang³

et al. 2023

Chem Biol Drug Des

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Nonalcoholic fatty liver disease (NAFLD) is a prevalent long‐term disease in the world. Liquiritigenin (LQ) is protective against a variety of hepatotoxins. Herein, we report the potential mechanism of LQ on a high‐fat diet (HFD) induced NAFLD. NAFLD mice model was established by HFD for 12 weeks, and LQ treatment for 1 week. Commercially available assay kits measure liver triglycerides (TG) and total cholesterol (TC) levels. Plasm TC, TG, high‐density‐lipoprotein (HDL‐C), and low‐density‐lipoprotein cholesterol (LDL‐C) levels were also monitored by biochemistry. Enzyme linked immunosorbent assay (ELISA) kits were performed to analyze the pro‐inflammatory factors, and intraperitoneal glucose tolerance test (IPGTT), insulin tolerance test (IPITT), and serum insulin were also determined. GO and KEGG pathway enrichment analysis was employed to analyze the overlapping genes of LQ targets and NAFLD development‐related targets. Western blot was performed on key proteins of the enriched signaling pathway. HFD mice showed significant increases in hepatic TG and TC, and plasm TC, TG, and LDL‐C in blood lipids, while HDL‐C significantly decreased, and LQ treatment reversed their levels (p < 0.05). LQ also alleviated HFD‐induced elevated levels of IPGTT, IPITT, and homeostasis model assessment of insulin resistance (HOMA‐IR). And serum levels of the pro‐inflammatory factor were also suppressed by LQ. PI3K/AKT pathway was enriched by KEGG pathway enrichment, and its key proteins p‐PI3K and p‐AKT were elevated after LQ treatment (p < 0.05). We found for the first time that LQ improves lipid accumulation, alleviates insulin resistance, and suppresses inflammatory responses in NAFLD mice, which might be associated with the activation of the PI3K/AKT pathway.

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Section: Discussionmentioning

confidence: 99%

Liquiritigenin regulates insulin sensitivity and ameliorates inflammatory responses in the nonalcoholic fatty liver by activation PI3K/AKT pathway

Bao¹,

Hao

Jiang³

et al. 2023

Chem Biol Drug Des

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“…The hindgut intestinal segment (i.e., caecum) of the animals in the four groups was dissected, rinsed with saline, and samples (tissue and intestinal fluid) were taken to be processed for microbiological examination. Caecum was the chosen intestinal segment due to its microbial diversity and abundance [ 54 , 55 ]. Intestinal tissue and fluid samples were diluted 1:1, immediately after being aseptically removed, in 25% glycerol-Ringer’s solution and stored at −80 °C until microbiological analysis.…”

Section: Methodsmentioning

confidence: 99%

Corinthian Currants Supplementation Restores Serum Polar Phenolic Compounds, Reduces IL-1beta, and Exerts Beneficial Effects on Gut Microbiota in the Streptozotocin-Induced Type-1 Diabetic Rat

et al. 2023

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The present study aimed at investigating the possible benefits of a dietary intervention with Corinthian currants, a rich source of phenolic compounds, on type 1 diabetes (T1D) using the animal model of the streptozotocin-(STZ)-induced diabetic rat. Male Wistar rats were randomly assigned into four groups: control animals, which received a control diet (CD) or a diet supplemented with 10% w/w Corinthian currants (CCD), and diabetic animals, which received a control diet (DCD) or a currant diet (DCCD) for 4 weeks. Plasma biochemical parameters, insulin, polar phenolic compounds, and inflammatory factors were determined. Microbiota populations in tissue and intestinal fluid of the caecum, as well as fecal microbiota populations and short-chain fatty acids (SCFAs), were measured. Fecal microbiota was further analyzed by 16S rRNA sequencing. The results of the study showed that a Corinthian currant-supplemented diet restored serum polar phenolic compounds and decreased interleukin-1b (IL-1b) (p < 0.05) both in control and diabetic animals. Increased caecal lactobacilli counts (p < 0.05) and maintenance of enterococci levels within normal range were observed in the intestinal fluid of the DCCD group (p < 0.05 compared to DCD). Higher acetic acid levels were detected in the feces of diabetic rats that received the currant diet compared to the animals that received the control diet (p < 0.05). Corinthian currant could serve as a beneficial dietary component in the condition of T1D based on the results coming from the animal model of the STZ-induced T1D rat.

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New aspects characterizing non-obese NAFLD by the analysis of the intestinal flora and metabolites using a mouse model

Zhang,

Cheng,

et al. 2024

mSystems

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Non-alcoholic fatty liver disease (NAFLD) is a major public health problem due to the high incidence affecting approximately one-third of the world’s population. NAFLD is usually linked to obesity and excessive weight. A subset of patients with NAFLD expresses normal or low body mass index; thus, the condition is called non-obese NAFLD or lean NAFLD. However, patients and healthcare professionals have little awareness and understanding of NAFLD in non-obese individuals. Furthermore, preclinical results from non-obese animal models with NAFLD are unclear. Gut microbiota and their metabolites in non-obese/lean-NAFLD patients differ from those in obese NAFLD patients. Therefore, we analyzed the biochemical indices, intestinal flora, and intestinal metabolites in a non-obese NAFLD mouse model established using a methionine-choline-deficient (MCD) diet. The significantly lean MCD mice had a remarkable fatty liver with lower serum triglyceride and free fatty acid levels, as well as higher alanine transaminase and aspartate transaminase levels than normal mice. 16S RNA sequencing of fecal DNA showed that the overall richness and diversity of the intestinal flora decreased in MCD mice, whereas the Firmicutes:Bacteroidota ratio was increased. g_ Tuzzerella , s_ Bifidobacterium pseudolongum , and s_ Faecalibaculum rodentium were the predominant species in non-obese NAFLD mice. Fecal metabolomics using liquid chromatography-tandem mass spectrometry revealed the potential biomarkers for the prognosis and diagnosis of non-obese NAFLD, including high levels of tyramine glucuronide, 9,12,13-TriHOME, and pantetheine 4′-phosphate, and low levels of 3-carbamoyl-2-phenylpropionaldehyde, N-succinyl-L,L-2,6-diaminopimelate, 4-methyl-5-thiazoleethanol, homogentisic acid, and estriol. Our findings could be useful to identify and develop drugs to treat non-obese NAFLD and lean NAFLD. IMPORTANCE Patients and healthcare professionals have little awareness and understanding of NAFLD in non-obese individuals. In fact, about 40% of people with NAFLD worldwide are non-obese, and nearly one-fifth are lean. Lean NAFLD unfortunately may be unnoticed for years and remains undetected until hepatic damage is advanced and the prognosis is compromised. This study focused on the lean NAFLD, screened therapeutic agents, and biomarkers for the prognosis and diagnosis using MCD-induced male C57BL/6J mice. The metabolites tyramine glucuronide, 9,12,13-TriHOME, and pantetheine 4′-phosphate, together with the predominant flora including g_ Tuzzerella , s_ Bifidobacterium pseudolongum , and s_ Faecalibaculum rodentium , were specific in non-obese NAFLD mice and might be used as targets for non-obese NAFLD drug exploration. This study is particularly significant for non-obese NAFLDs that need to be more actively noticed and vigilant.

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Characteristics of intestinal microbiota in C57BL/6 mice with non-alcoholic fatty liver induced by high-fat diet

Cited by 3 publications

References 57 publications

Liquiritigenin regulates insulin sensitivity and ameliorates inflammatory responses in the nonalcoholic fatty liver by activation PI3K/AKT pathway

Liquiritigenin regulates insulin sensitivity and ameliorates inflammatory responses in the nonalcoholic fatty liver by activation PI3K/AKT pathway

Corinthian Currants Supplementation Restores Serum Polar Phenolic Compounds, Reduces IL-1beta, and Exerts Beneficial Effects on Gut Microbiota in the Streptozotocin-Induced Type-1 Diabetic Rat

New aspects characterizing non-obese NAFLD by the analysis of the intestinal flora and metabolites using a mouse model

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