Baicalein reduces hepatic fat accumulation by activating AMPK in oleic acid-induced HepG2 cells and high-fat diet-induced non-insulin-resistant mice

2020 ◽  
Vol 11 (1) ◽  
pp. 711-721
Author(s):  
Wenlong Sun ◽  
Panpan Liu ◽  
Tianqi Wang ◽  
Xudong Wang ◽  
Weilong Zheng ◽  
...  
Keyword(s):  
Oleic Acid ◽  
Liver Disease ◽  
High Fat Diet ◽  
Hepg2 Cells ◽  
Fatty Liver Disease ◽  
High Fat ◽  
Fat Accumulation ◽  
Nonalcoholic Fatty Liver ◽  
Insulin Resistant ◽  
Hepatic Fat

Nonalcoholic fatty liver disease (NAFLD) has become the most common liver disease worldwide; thus, a dietary supplement that can restrict hepatic fat accumulation is needed.

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.

scholarly journals Sheng-Jiang Powder Ameliorates High Fat Diet Induced Nonalcoholic Fatty Liver Disease via Inhibiting Activation of Akt/mTOR/S6 Pathway in Rats

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Juan Li ◽  
Lv Zhu ◽  
Yu-mei Zhang ◽  
Huan Chen ◽  
Yi-fan Miao ◽  
...  
Keyword(s):  
Oleic Acid ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
High Fat Diet ◽  
Fatty Liver Disease ◽  
Lipid Droplets ◽  
Cell Cancer ◽  
High Fat ◽  
Nonalcoholic Fatty Liver

Background and Aims. Nonalcoholic fatty liver disease (NAFLD) is an alarming public health problem that directly contributes to increased prevalence of liver cirrhosis and hepatic cell cancer, but without any specific pharmacological option. Sheng-jiang powder (SJP), an empirical Chinese medicine formula to treat NAFLD, showed great efficacy but the specific mechanisms have never been reported. Therefore, we performed this study to explore the effect of SJP on NAFLD and the potential mechanism.Methods. NAFLD was induced by high fat diet (HFD) feeding. Rats were treated with SJP/normal saline daily for 10 weeks and all rats were euthanized after 12 weeks’ feeding. Liver tissue samples were obtained for biochemistry test and pathological evaluation. Additionally, oleic acid induced LO2 cells were employed to simulate a cell model of NAFLD. Cells were subjected to western blotting for Akt, mTOR, S6, SREBP1-c, and FASN detection after coincubated with SJP, LY294002 (a selective PI3K inhibitor), or the combination for 24h.Results. HFD significantly induced hepatic steatosis. Plenty of lipid droplets were observed under transmission electron microscope. The ultrastructure of liver cells showed distinct changes with obvious endoplasmic reticulum expansion, mitochondrial contraction, and cell matrix solidification. Although no difference was detected in serum hepatic enzymes and tissue proinflammatory cytokines, the tissue level of SOD and GSH-px was much lower and the pathologic injuries were much severe in HFD feeding rats. However, SJP treatment significantly attenuated the ultrastructure changes and protected rat liver against inflammatory injury. Abundant of lipid droplets and high expression of pAkt, pmTOR, pS6, and FASN were observed in oleic acid treated LO2 cells, while these changes were restored by SJP treatment.Conclusions. SJP is efficient in attenuating HFD induced NAFLD in rats and this effect might be partly related to the inhibition of Akt/mTOR/S6 pathway.

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 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.

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