scholarly journals Chicoric Acid Ameliorates Nonalcoholic Fatty Liver Disease via the AMPK/Nrf2/NFκB Signaling Pathway and Restores Gut Microbiota in High-Fat-Diet-Fed Mice

2020 ◽  
Vol 2020 ◽  
pp. 1-20
Author(s):  
Xiaoqin Ding ◽  
Tunyu Jian ◽  
Jiawei Li ◽  
Han Lv ◽  
Bei Tong ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Disease ◽  
Gut Microbiota ◽  
Fatty Liver ◽  
Protein Level ◽  
High Fat Diet ◽  
Hepg2 Cells ◽  
Fatty Liver Disease ◽  
High Fat ◽  
Nonalcoholic Fatty Liver

This study examines the effects of chicoric acid (CA) on nonalcoholic fatty liver disease (NAFLD) in high-fat-diet- (HFD-) fed C57BL/6 mice. CA treatment decreased body weight and white adipose weight, mitigated hyperglycemia and dyslipidemia, and reduced hepatic steatosis in HFD-fed mice. Moreover, CA treatment reversed HFD-induced oxidative stress and inflammation both systemically and locally in the liver, evidenced by the decreased serum malondialdehyde (MDA) abundance, increased serum superoxide dismutase (SOD) activity, lowered in situ reactive oxygen species (ROS) in the liver, decreased serum and hepatic inflammatory cytokine levels, and reduced hepatic inflammatory cell infiltration in HFD-fed mice. In addition, CA significantly reduced lipid accumulation and oxidative stress in palmitic acid- (PA-) treated HepG2 cells. In particular, we identified AMPK as an activator of Nrf2 and an inactivator of NFκB. CA upregulated AMPK phosphorylation, the nuclear protein level of Nrf2, and downregulated NFκB protein level both in HFD mice and PA-treated HepG2 cells. Notably, AMPK inhibitor compound C blocked the regulation of Nrf2 and NFκB, as well as ROS overproduction mediated by CA in PA-treated HepG2 cells, while AMPK activator AICAR mimicked the effects of CA. Similarly, Nrf2 inhibitor ML385 partly blocked the regulation of antioxidative genes and ROS overproduction by CA in PA-treated HepG2 cells. Interestingly, high-throughput pyrosequencing of 16S rRNA suggested that CA could increase Firmicutes-to-Bacteroidetes ratio and modify gut microbial composition towards a healthier microbial profile. In summary, CA plays a preventative role in the amelioration of oxidative stress and inflammation via the AMPK/Nrf2/NFκB signaling pathway and shapes gut microbiota in HFD-induced NAFLD.

scholarly journals CYP2J2 overexpression attenuates nonalcoholic fatty liver disease induced by high-fat diet in mice

2015 ◽  
Vol 308 (2) ◽  
pp. E97-E110 ◽  
Author(s):  
Guangzhi Chen ◽  
Renfan Xu ◽  
Shasha Zhang ◽  
Yinna Wang ◽  
Peihua Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Disease ◽  
Fatty Liver ◽  
High Fat Diet ◽  
Hepg2 Cells ◽  
Fatty Liver Disease ◽  
High Fat ◽  
Jnk Signaling ◽  
Nonalcoholic Fatty Liver ◽  
And Oxidative Stress

Cytochrome P-450 epoxygenase-derived epoxyeicosatrienoic acids (EETs) exert diverse biological activities, which include potent vasodilatory, anti-inflammatory, antiapoptotic, and antioxidatant effects, and cardiovascular protection. Liver has abundant epoxygenase expression and high levels of EET production; however, the roles of epoxygenases in liver diseases remain to be elucidated. In this study, we investigated the protection against high-fat diet-induced nonalcoholic fatty liver disease (NAFLD) in mice with endothelial-specific CYP2J2 overexpression (Tie2-CYP2J2-Tr). After 24 wk of high-fat diet, Tie2-CYP2J2-Tr mice displayed attenuated NAFLD compared with controls. Tie2-CYP2J2-Tr mice showed significantly decreased plasma triglyceride levels and liver lipid accumulation, improved liver function, reduced inflammatory responses, and less increase in hepatic oxidative stress than wild-type control mice. These effects were associated with inhibition of NF-κB/JNK signaling pathway activation and enhancement of the antioxidant defense system in Tie2-CYP2J2-Tr mice in vivo. We also demonstrated that 14,15-EET treatment protected HepG2 cells against palmitic acid-induced inflammation and oxidative stress. 14,15-EET attenuated palmitic acid-induced changes in NF-κB/JNK signaling pathways, malondialdehyde generation, glutathione levels, reactive oxygen species production, and NADPH oxidase and antioxidant enzyme expression in HepG2 cells in vitro. Together, these results highlight a new role for CYP epoxygenase-derived EETs in lipotoxicity-related inflammation and oxidative stress and reveal a new molecular mechanism underlying EETs-mediated anti-inflammatory and antioxidant effects that could aid in the design of new therapies for the prevention and treatment of NAFLD.

Alleviating effects of noni fruit polysaccharide on hepatic oxidative stress and inflammation in rats under a high-fat diet and its possible mechanisms

2020 ◽  
Vol 11 (4) ◽  
pp. 2953-2968 ◽  
Author(s):  
Xiaobing Yang ◽  
Wenjing Mo ◽  
Chuanjin Zheng ◽  
Wenzhi Li ◽  
Jian Tang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Disease ◽  
Gut Microbiota ◽  
Fatty Liver ◽  
High Fat Diet ◽  
Fatty Liver Disease ◽  
High Fat ◽  
Alcoholic Fatty Liver ◽  
Hepatic Oxidative Stress ◽  
Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease is associated with gut microbiota, oxidative stress, and inflammation.

Aromatic aldehyde compound cuminaldehyde protects nonalcoholic fatty liver disease in rats feeding high fat diet

2019 ◽  
Vol 38 (7) ◽  
pp. 823-832 ◽  
Author(s):  
MR Haque ◽  
SH Ansari
Keyword(s):  
Oxidative Stress ◽  
Liver Disease ◽  
Fatty Liver ◽  
High Fat Diet ◽  
Fatty Liver Disease ◽  
Liver Enzymes ◽  
Liver Weight ◽  
High Fat ◽  
Nonalcoholic Fatty Liver ◽  
And Oxidative Stress

Nonalcoholic fatty liver disease (NAFLD) is caused by fat accumulation and is related with obesity and oxidative stress. In this study, we investigated the effect of cuminaldehyde on NAFLD in rats fed a high fat diet (HFD). Male Wistar rats were fed a HFD for 42 days to induce NAFLD. The progression of NAFLD was evaluated by histology and measuring liver enzymes (alanine transaminase and aspartate transaminase), serum and hepatic lipids (total triglycerides and total cholesterol), and oxidative stress markers (thiobarbituric acid reactive substances, glutathione, superoxide dismutase, and catalase). The HFD feeding increased the liver weight and caused NAFLD, liver steatosis, hyperlipidemia, oxidative stress, and elevated liver enzymes. Administration of cuminaldehyde ameliorated the changes in hepatic morphology and liver weight, decreased levels of liver enzymes, and inhibited lipogenesis. Our findings suggest that cuminaldehyde could improve HFD-induced NAFLD via abolishment of hepatic oxidative damage and hyperlipidemia. Cuminaldehyde might be considered as a potential aromatic compound in the treatment of NAFLD and obesity through the modulation of lipid metabolism.

scholarly journals Liraglutide Attenuates Nonalcoholic Fatty Liver Disease by Modulating Gut Microbiota in Rats Administered a High-Fat Diet

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Ningjing Zhang ◽  
Junxian Tao ◽  
Lijun Gao ◽  
Yan Bi ◽  
Ping Li ◽  
...  
Keyword(s):  
Liver Disease ◽  
Gut Microbiota ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Hepatic Steatosis ◽  
High Fat Diet ◽  
Fatty Liver Disease ◽  
Structural Changes ◽  
High Fat ◽  
Nonalcoholic Fatty Liver

This study aimed to determine whether modulation of the gut microbiota structure by liraglutide helps improve nonalcoholic fatty liver disease (NAFLD) in rats on a high-fat diet (HFD). Rats were administered an HFD for 12 weeks to induce NAFLD and then administered liraglutide for 4 additional weeks. Next-generation sequencing and multivariate analysis were performed to assess structural changes in the gut microbiota. Liraglutide attenuated excessive hepatic ectopic fat deposition, maintained intestinal barrier integrity, and alleviated metabolic endotoxemia in HFD rats. Liraglutide significantly altered the overall structure of the HFD-disrupted gut microbiota and gut microbial composition in HFD rats in comparison to those on a normal diet. An abundance of 100 operational taxonomic units (OTUs) were altered upon liraglutide administration, with 78 OTUs associated with weight gain or inflammation. Twenty-three OTUs positively correlated with hepatic steatosis-related parameters were decreased upon liraglutide intervention, while 5 OTUs negatively correlated with hepatic steatosis-related parameters were increased. These results suggest that liraglutide-mediated attenuation of NAFLD partly results from structural changes in gut microbiota associated with hepatic steatosis.

scholarly journals Da-Chai-Hu Decoction Ameliorates High Fat Diet-Induced Nonalcoholic Fatty Liver Disease Through Remodeling the Gut Microbiota and Modulating the Serum Metabolism

2020 ◽  
Vol 11 ◽  
Author(s):  
Huantian Cui ◽  
Yuting Li ◽  
Yuming Wang ◽  
Lulu Jin ◽  
Lu Yang ◽  
...  
Keyword(s):  
Liver Disease ◽  
16S Rrna ◽  
Gut Microbiota ◽  
Fatty Liver ◽  
Metabolic Pathways ◽  
High Fat Diet ◽  
Fatty Liver Disease ◽  
High Fat ◽  
Nonalcoholic Fatty Liver ◽  
Rrna Sequencing

The dysbiosis in gut microbiota could affect host metabolism and contribute to the development of nonalcoholic fatty liver disease (NAFLD). Da-Chai-Hu decoction (DCH) has demonstrated protective effects on NAFLD, however, the exact mechanisms remain unclear. In this study, we established a NAFLD rat model using a high fat diet (HFD) and provided treatment with DCH. The changes in gut microbiota post DCH treatment were then investigated using 16S rRNA sequencing. Additionally, serum untargeted metabolomics were performed to examine the metabolic regulations of DCH on NAFLD. Our results showed that DCH treatment improved the dyslipidemia, insulin resistance (IR) and ameliorated pathological changes in NAFLD model rats. 16S rRNA sequencing and untargeted metabolomics showed significant dysfunction in gut microbiota community and serum metabolites in NAFLD model rats. DCH treatment restored the dysbiosis of gut microbiota and improved the dysfunction in serum metabolism. Correlation analysis indicated that the modulatory effects of DCH on the arachidonic acid (AA), glycine/serine/threonine, and glycerophospholipid metabolic pathways were related to alterations in the abundance of Romboutsia, Bacteroides, Lactobacillus, Akkermansia, Lachnoclostridium and Enterobacteriaceae in the gut microflora. In conclusion, our study revealed the ameliorative effects of DCH on NAFLD and indicated that DCH’s function on NAFLD may link to the improvement of the dysbiosis of gut microbiota and the modulation of the AA, glycerophospholipid, and glycine/serine/threonine metabolic pathways.

scholarly journals Gut Microbiota Mediates the Protective Effects of Andrographolide Inhibits Inflammation and Nonalcoholic Fatty Liver Disease(NAFLD) in High-Fat Diet induced ApoE(-/-) Mice

2020 ◽  
Author(s):  
Shuai Shi ◽  
Xin-Yu Ji ◽  
Jing-Jing Shi ◽  
Shu-Qing Shi ◽  
Qiu-Lei Jia ◽  
...  
Keyword(s):  
Liver Disease ◽  
16S Rrna ◽  
Gut Microbiota ◽  
High Fat Diet ◽  
Hepg2 Cells ◽  
Fatty Liver Disease ◽  
High Fat ◽  
Nonalcoholic Fatty Liver ◽  
Microbial Dysbiosis ◽  
Ppar Γ

AbstractMechanisms relating the gut bacteria to Nonalcoholic Fatty Liver Disease (NAFLD) have been proposed containing the dysbiosis-induced dysregulation of hepatic lipid metabolism that allows for the translocation of microbial components and leads to hepatic inflammation and steatosis. Andrographolide (AG) regulates inflammation mediated by NF-κB pathway which also play a key role in reduction of inflammation and fibrosis in experimental nonalcoholic steatohepatitis (NASH), yet the mechanisms linking this effect to gut microbiota remain obscure. Here we show that ApoE knockout (Apoe -/-) mice fed a high-fat diet (HFD) supplemented with AG regulates levels of biochemical index and inflammatory cytokines associated with gut microbe. Moreover, HEPG2 cells induced by ox-LDL were used as validation in vitro. H&E staining and Oil-Red staining were respectively used for tissue and cells morphology. Gut microbiota were examined by 16S rRNA sequencing. Expression of NF-κB, C/EBPβ and PPAR-γ in liver and HEPG2 cells were detected by western blot and qRT-PCR. The results showed, among others, that AG alleviate hepatic steatosis and fat content in HEPG2 cells, while it induced decreased levels of Bacteroides, and increased levels of Faecalibaculum, Akkermansia. We further identified that inhibition of NF-κB/C/EBPβ/PPAR-γ pathway of hepatic steatosis model in vivo and vitro by AG also contributes to prevention of HFD-induced inflammation and dislipidemia. Importantly, as result of pearson correlation, Bacteroides may be the most relevant one fundamentally involved in the mechanism of AG attenuates NAFLD. Together, our findings uncover an interaction between AG and gut microbiota as a novel mechanism for the anti-NAFLD effect of AG acting through prevention of microbial dysbiosis, dislipidemia and inflammation.ImportanceHFD due to gut microbial dysbiosis is a major contributor to the pathogenesis of dislipidemia and inflammation, which primarily mediates the development of NAFLD. A treatment strategy to reduce both dislipidemia and inflammation appears to be an effective approach for addressing the issue of NAFLD. Andrographolide (AG) is the major effect component in traditional Chinese medicine Chuan-xin-lian (Andrographis). Little is known about the role of gut microbiota in the anti-NAFLD effect of AG. 16S rRNA gene sequencing revealed that AG significantly decreased Bacteroides and increased Faecalibaculum, Akkermansia. By using vivo and vitro experiment, we prove that gut microbiota plays a key role in AG-induced protective against high-fat-diet-induced dislipidemia and inflammation. Moreover, NF-κB/C/EBPβ/PPAR-γ pathway inhibition was partially involved in the beneficial effect of AG. Together, these data suggest that the gut microbiome is a critical factor for the anti-NAFLD effects of AG.

scholarly journals Lingguizhugan Decoction Protects against High-Fat-Diet-Induced Nonalcoholic Fatty Liver Disease by Alleviating Oxidative Stress and Activating Cholesterol Secretion

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Lili Yang ◽  
Weili Lin ◽  
Colleen A. Nugent ◽  
Shijun Hao ◽  
Haiyan Song ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Disease ◽  
Fatty Liver ◽  
Real Time Pcr ◽  
High Fat Diet ◽  
Fatty Liver Disease ◽  
High Fat ◽  
Nonalcoholic Fatty Liver ◽  
Global Transcriptome ◽  
Cholesterol Secretion

Background. Nonalcoholic fatty liver disease (NAFLD) has become a leading cause of liver transplantation. Lingguizhugan decoction (LGZG), a classical Chinese herbal formula, has beneficial effects on NAFLD animal models. Our study examined the impact of LGZG on hepatic global transcriptome of high-fat-diet-induced NAFLD rats. Methods. Three groups of Wistar rats were included: normal, NAFLD model, and LGZG-treated NAFLD groups. Four weeks for the treatment, liver tissues were harvested for RNA sequencing. Differentially expressed genes (DEGs) and enriched pathways were detected on hepatic global transcriptome profile. Real-time PCR validated the regulatory patterns of LGZG on NAFLD rats. Results. DEGs between the NAFLD model and normal groups indicated the elevated peroxisome proliferator-activated receptor (PPAR) and hedgehog signaling pathways in NAFLD rats. In bile secretion pathway, genes involved in cholesterol secretion were activated by LGZG treatment. Increased expression of antioxidant OSIGN1 and decreased expression of genes (AHR, IRF2BP2, and RASGEF1B) that induce oxidative stress and inflammation were observed in NAFLD rats treated with LGZG. The regulatory patterns of LGZG treatment on these oxidative stress-related genes were confirmed by real-time PCR. Conclusion. Our study revealed a “two-hits-targeting” mechanism of LGZG in the treatment for NAFLD: alleviating oxidative stress and activating cholesterol secretion.

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