Alcoholic fatty liver disease inhibited the co-expression of Fmo5 and PPARα to activate the NF-κB signaling pathway, thereby reducing liver injury via inducing gut microbiota disturbance

Kong, Ling; Chen, Jing; Ji, Xiao li; Qin, Qian; Yang, Hui; Liú, Dan; Li, De liang; Sun, Mei ling

doi:10.21203/rs.3.rs-40866/v1

Cited by 5 publications

(6 citation statements)

References 17 publications

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“…PPAR is a core factor in the anti-inflammatory response pathway and participates in the formation of inflammatory and metabolic signal regulatory networks by different pathways, thus significantly affecting the regulation of glucolipid metabolism. PPARγ also can reduce the expression of NF-κB-mediated inflammatory mediators and exert its anti-inflammatory effect (35). PPARγ regulate the expression of many fat and inflammatory factors such as TNFα and regulate the glucolipid metabolism process (36).…”

Section: Discussionmentioning

confidence: 99%

Multiomic analysis of dark tea extract on glycolipid metabolic disorders in db/db mice

Wang

et al. 2022

Front. Nutr.

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Glycolipid metabolic disorder is a serious threat to human health. Dark tea is a kind of traditional Chinese tea, which may regulate the glycolipid metabolic disorders. Dark tea extract (DTE) is the water extraction obtained from dark tea. Compared with traditional dark tea, DTE has the benefits of convenient consumption and greater potential for promoting health. However, the regulation of DTE on glycolipid metabolism and its molecular mechanism is rarely investigated. In our study, DTE was used as raw material to study the effect and molecular mechanism of its intervention on the glycolipid metabolic in db/db diabetic mice by using multiomics analysis and modern biological techniques. (1) DTE could significantly reduce fasting glucose in diabetic db/db mice, and the higher dose group has a better effect. Histopathological examination showed that DTE slightly improve the number of islets and decrease the number of islet β cells in the pancreatic tissue in db/db mice. (2) RNA-Seq was used to analyze the gene expression in liver tissue. In terms of biological processes, DTE mainly affected the inflammation and fatty acid metabolism. In terms of cell components, the lipoprotein and respiratory chain are mainly affected. In the aspect of molecular function, DTE mainly affected the redox related enzyme activity, iron ion binding and glutathione transferase. Arachidonic acid metabolism pathway, glutathione metabolism and PPAR signaling pathway were enriched by DTE with the results of KEGG pathway enrichment. In addition, real-time PCR results confirmed that DTE could significantly activate key genes of PPAR signaling pathway like Fabp1, Cyp4a1, Ehhadh, Cyp4a32, Aqp7 and Me1. (3) 16s rDNA showed that DTE could significantly decrease the ratio of Firmicutes/Bacteroidetes and the abundance of Proteobacteria, and increased the relative abundance of Verrucomicrobia at the phylum level. At the genus level, the relative abundance of Akkermansia, Prevotellaceae, Bacteroides and Alloprevotella was significantly increased after DTE treatment. This study provides multiomics molecular evidence for the intervention effect of DTE on abnormal glucose and lipid metabolism and the application of precise nutritional diet intervention of dark tea extract.

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Section: Discussionmentioning

confidence: 99%

Multiomic analysis of dark tea extract on glycolipid metabolic disorders in db/db mice

Wang

et al. 2022

Front. Nutr.

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“…Reduction of the diversity of gut microbiota was induced in a microinflammatory state and accelerated the micro-ecological imbalance (49). This could directly affect the function of intestinal microbes and abnormal liver-related function, which could result in a discrepancy in treatment outcomes (50,51).…”

Section: Discussionmentioning

confidence: 99%

Operable hepatitis B virus-related hepatocellular carcinoma: gut microbiota profile of patients at different ages

Peng¹,

Xu²,

Zeng³

et al. 2022

Ann Transl Med

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Background: Age was important prognostic factors for operable hepatocellular carcinoma patients. The aim of the present study was to assess the difference in gut microbiota in patients with operable hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) at different ages ; to investigate the features of the microbiota and its function associated with different ages; to provide a preliminary look at effects of the gut microbiota dimension on prognostic.Methods: From September 2020 to May 2021, patients with HBV-HCC were able to undergo liver resection and were recruited consecutively and divided into the younger age group (age <45 years) (Y.AG) (n=20), middle age group (age from 45 to 65 years) (M.AG) (n=13) 45-65 years, and older age group (age >65 years) (O.AG) (n=20). The relationships between gut microbiota and different ages were explored using 16S rRNA gene sequencing data. PICRUST2 was used to examine the metagenomic data in PHLF patients.Fisher's exact and Mann-Whitney U-test were used for the data analysis.Results: Pairwise comparison between the three groups showed that the α-diversity of Y.AG was significantly higher than that of O.AG (ACE Index, P=0.017; chao1 Index, P=0.031; observed_species Index, P=0.011; and goods_coverage Index, P=0.041). The β-diversity in the 3 groups differed significantly (stress =0.100), while the composition (β-diversity) differed significantly between the Y.AG and the M.AG (stress =0.090), the M.AG and the O.AG (stress =0.095), and the Y.AG and the O.AG (stress =0.099). At the genus level, 7 bacterial genera were significantly enriched in the O.AG compared with the Y.AG, of which Streptococcus, Blautia, Erysipelotrichaceae_UCG-003, and Fusicatenibacter represented the major variances in O.AG microbiomes. Eleven genera were significantly increased in the O.AG, of which Prevotella, Allorhizobium-Neorhizobium-Pararhizobium-Rhizobium, Ruminiclostridium, and Phascolarctobacterium represented the major variances in the O.AG. The Y.AG and the O.AG were predicted by PICRUSt2 analysis, which found 72 pathways related to differential gut microbiome at the genus level. Redundancy analysis showed that 7 environmental factors were significantly correlated with intestinal microorganisms, especially in the Y.AG compared with the O.AG. Conclusions: Analysis of gut microbiota characteristics in patients of different ages could ultimately contribute to the development of novel avenues for the treatment of HCC at different ages.

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“…AFLD is associated with lipid metabolism disorder and insulin resistance which lead to alcoholic steatosis [41,42]. Alcohol consumption leads to fatty acid synthesis increase (upregulate SREBP1c in liver [43]) and decrease of fatty acid transport and oxidation (downregulate PPARα [44] and mitochondrial β-oxidation [45]) as the ' rst hit', and chronic alcohol inhibits lipophagy though may activate when acute alcohol administration as a compensatory to against alcoholic liver injury[46, 47].…”

Section: Discussionmentioning

confidence: 99%

Improvement Lipophagy by Restoring Rab7 Cycle: Protective Effects of Quercetin on Ethanol-Induced Liver Steatosis

Lin

Guo

Liu

et al. 2021

Preprint

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Background: Chronic alcohol consumption induces lipophagy retard which contributes the pathogenesis of liver steatosis. Lipophagy-related Rab7 responsible for the fusion between autophagosomes and lysosomes has been presumed as a crucial regulator on the progression of alcohol liver disease (ALD) despite elusive mechanisms. More importantly, whether hepatoprotective quercetin targets Rab7-associated lipophagy disorder or not, still remains uncertain. Results: ALD mice were induced by chronic-plus-single-binge ethanol feeding that manifested by hampering autophagosomes formation with lipid droplets (LDs) and fuse with lysosomes compared with the normal control, which was normalized partially by quercetin. GST-RILP pulldown assay of Rab7 indicated an improved GTP-Rab7 as quercetin treatment for ethanol-feeding mice. Lipophagy was blocked when HepG2 cells were transfected with siRNA-Rab7, which was reversed through co-transfection of Rab7Wt plasmid. Rab7-specific inhibitor CID1067700 aggravated ethanol-induced steatosis and autophagic flux disruption visualized by immunofluorescence co-localization analysis and mCherry-GFP-LC3 transfection. HepG2 cells overexpressing Rab7Wt show a stronger alleviation on alcohol-induced lipophagy dysfunction than Rab7Q67L. Furthermore, TBC1D5 responsible for Rab7 inactivation was downregulated after alcohol administration, but regained by quercetin. Rab7 circulation retarded by ethanol and corrected by quercetin was further revealed by fluorescence recovery after photobleaching (FRAP). Conclusions: Chronic alcoholic not only inactivates Rab7 but also retards TBC1D5-mediated Rab7 turnover, synergistically obstructing lipophagy flux and promoting ethanol-induced steatosis. Quercetin attenuates adipohepatic degeneration by normalizing ethanol-imposed Rab7 disorders and subsequent lipophagy disturbance, highlighting a novel mechanism and promising prospect of quercetin-like phytochemicals against the crucial first hit from the alcohol.

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Alcoholic fatty liver disease inhibited the co-expression of Fmo5 and PPARα to activate the NF-κB signaling pathway, thereby reducing liver injury via inducing gut microbiota disturbance

Cited by 5 publications

References 17 publications

Multiomic analysis of dark tea extract on glycolipid metabolic disorders in db/db mice

Multiomic analysis of dark tea extract on glycolipid metabolic disorders in db/db mice

Operable hepatitis B virus-related hepatocellular carcinoma: gut microbiota profile of patients at different ages

Improvement Lipophagy by Restoring Rab7 Cycle: Protective Effects of Quercetin on Ethanol-Induced Liver Steatosis

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