Sirt1 Promotes the Restoration of Hepatic Progenitor Cell (HPC)-Mediated Liver Fatty Injury in NAFLD Through Activating the Wnt/β-Catenin Signal Pathway

Non-alcoholic fatty liver disease (NAFLD) has developed into the world's largest chronic epidemic. In NAFLD, hepatic steatosis causes hepatocytes dysfunction and even apoptosis. The liver has a strong restoration or regeneration ability after an injury, however, it is unclear through which pattern fatty liver injury in NAFLD is repaired and what the repair mechanism is. Here, we found that in the high-fat diet (HFD)-induced NAFLD mice model, fatty liver injury caused the significant ductular reaction (DR), which is a marker to promote the repair of liver injury. SOX9+ and HNF4α+ biphenotype also suggested that hepatic progenitor cells (HPCs) were activated by fatty liver injury in the HFD-elicited NAFLD mice model. Concurrently, fatty liver injury also activated the Wnt/β-catenin signal pathway, which is a necessary process for HPC differentiation into mature hepatocytes. However, Sirt1 knockdown weakened HPC activation and Wnt/β-catenin signal in Sirt1+/− mice with HFD feeding. In rat-derived WB-F344 hepatic stem cell line, Sirt1 overexpression (OE) or Sirt1 activator–Resveratrol promoted HPC differentiation via activating Wnt/β-catenin signal pathway. Glycogen PAS staining demonstrated that Sirt1 OE promoted WB-F344 cells to differentiate into mature hepatocytes with glycogen synthesis ability, while Sirt1 inhibitor EX527 or Wnt/β-catenin pathway inhibitor HF535 decreased glycogen positive cells. Together, our data suggested that Sirt1 plays a vital role in activating HPCs to repair fatty liver injury or promote liver regeneration through the Wnt/β-catenin signal pathway in NAFLD, which might provide a new strategy for fatty liver injury or NAFLD therapy.

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PO-103 The mechanism of long-term regular exercise intervention on liver injury in patients with NAFLD based on miR-146a regulation of TLR4/NF-KB signaling pathway

Exercise Biochemistry Review ◽

10.14428/ebr.v1i4.8823 ◽

2018 ◽

Vol 1 (4) ◽

Author(s):

Qi Peng ◽

Jiaqin Chen ◽

Wei Chen ◽

Chang Feng Shao ◽

Afang Yuan

Keyword(s):

Liver Fibrosis ◽

Liver Injury ◽

Fatty Liver ◽

Signaling Pathway ◽

Exercise Intervention ◽

Exercise Group ◽

Control Group ◽

Regular Exercise ◽

Alcoholic Fatty Liver

Objective To investigate the effects of long-term regular exercise on hepatic function in patients with non-alcoholic fatty liver (NAFLD) using blood biochemistry and liver fibrosis markers, and to compare the differential expression of cytokines related to TLR4/NF-KB signaling pathway. A preliminary discussion was made on its regulation mechanism. Methods Forty patients with NAFLD diagnosed in the Hunan Normal University School of Medicine, according to the degree of steatosis and exercise intervention, the patients were divided into control group (NAFLD group) 20 cases and long-term regular exercise group 20 cases, and the same time in our hospital Twenty patients with physical examination were normal controls; general data of all subjects, ALT, AST, GGT, serum type III procollagen (PCIII), hyaluronan (HA), and type IV collagen (CIV) were examined; Fluorescent quantitative PCR was used to detect the differential expression of TLR4/NF-KB signaling pathway-related cytokines and miR-146a in the blood of each group of subjects, revealing the effects and possible mechanisms of long-term regular exercise on liver fibrosis. Results Compared with the normal group, the levels of serum ALT, AST, GGT, PCIII, HA, and CIV in the non-alcoholic fatty liver patients were significantly lower in the long-term regular exercise group than in the control group; blood TLR4, NF-KB, MY-D88 Compared with the control group, the gene expression level was significantly downregulated in the long-term regular exercise group. Conclusions Long-term regular exercise can effectively reduce nonalcoholic inflammatory liver injury and has a clear anti-fibrotic effect. Its mechanism may be related to long-term regular exercise through regulating the TLR4/NF-KB signaling pathway related factors and the regulation of molecular miR-146a, reducing inflammation and preventing the formation of fibrosis.

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Serum adipokine levels predictive of liver injury in non-alcoholic fatty liver disease

Liver International ◽

10.1111/j.1478-3231.2009.02022.x ◽

2009 ◽

Vol 29 (9) ◽

pp. 1431-1438 ◽

Cited By ~ 90

Author(s):

Maud Lemoine ◽

Vlad Ratziu ◽

Minji Kim ◽

Mustapha Maachi ◽

Dominique Wendum ◽

...

Keyword(s):

Liver Disease ◽

Liver Injury ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Alcoholic Fatty Liver ◽

Alcoholic Fatty Liver Disease

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Use of an animal model to test whether non-alcoholic fatty liver disease increases the risk of idiosyncratic drug-induced liver injury

Journal of Immunotoxicology ◽

10.1080/1547691x.2018.1467982 ◽

2018 ◽

Vol 15 (1) ◽

pp. 90-95 ◽

Cited By ~ 5

Author(s):

Alastair Mak ◽

Tiffany Cho ◽

Jack Uetrecht

Keyword(s):

Animal Model ◽

Liver Disease ◽

Liver Injury ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Drug Induced ◽

Alcoholic Fatty Liver ◽

Drug Induced Liver Injury ◽

Alcoholic Fatty Liver Disease

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Diet containing dehulled adlay ameliorates hepatic steatosis, inflammation and insulin resistance in rats with non-alcoholic fatty liver disease

British Journal Of Nutrition ◽

10.1017/s0007114521003366 ◽

2021 ◽

pp. 1-25

Author(s):

Wan-Ju Yeh ◽

Jung Ko ◽

Wei-Yi Cheng ◽

Hsin-Yi Yang

Keyword(s):

Insulin Resistance ◽

Liver Disease ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Liver Weight ◽

Vital Role ◽

High Dose ◽

Alcoholic Fatty Liver ◽

Protein Levels ◽

Alcoholic Fatty Liver Disease

Abstract Dietary modification plays a vital role in the treatment of non-alcoholic liver diseases. We investigated the effects of the consumption of different amount of dehulled adlay, which has hypolipidemic and anti-inflammatory properties, on non-alcoholic fatty liver disease (NAFLD). We fed rats a high-fat-high-fructose liquid diet for 16 weeks to induce NAFLD. The rats were divided into three groups fed the NAFLD diet only (NN) or a diet containing 44.9 g/L or 89.8 g/L of dehulled adlay (group NA and NB, respectively). After 8 weeks, the NA & NB group had lower C-reactive protein levels and improvement in insulin resistance. In addition, the NB group had lower liver weight and hepatic triglyceride and cholesterol concentrations than did the NN group. Compared with the NN group, the high-dose NB group had improved steatosis, lower hepatic TNF-α, IL-1β and IL-6 levels, and lower adipose leptin levels. Our results suggest that a diet containing dehulled adlay can ameliorate NAFLD progression by decreasing of insulin resistance, steatosis and inflammation.

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Antrodan Alleviates High-Fat and High-Fructose Diet-Induced Fatty Liver Disease in C57BL/6 Mice Model via AMPK/Sirt1/SREBP-1c/PPARγ Pathway

International Journal of Molecular Sciences ◽

10.3390/ijms21010360 ◽

2020 ◽

Vol 21 (1) ◽

pp. 360 ◽

Cited By ~ 6

Author(s):

Charng-Cherng Chyau ◽

Hsueh-Fang Wang ◽

Wen-Juan Zhang ◽

Chin-Chu Chen ◽

Shiau-Huei Huang ◽

...

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Mice Model ◽

High Fat ◽

Alcoholic Fatty Liver ◽

High Fructose Diet ◽

High Fructose ◽

Ant Control ◽

Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) and -steatohepatitis (NASH) imply a state of excessive fat built-up in livers with/or without inflammation and have led to serious medical concerns in recent years. Antrodan (Ant), a purified β-glucan from A. cinnamomea has been shown to exhibit tremendous bioactivity, including hepatoprotective, antihyperlipidemic, antiliver cancer, and anti-inflammatory effects. Considering the already well-known alleviating bioactivity of A. cinnamomea for the alcoholic steatohepatitis (ASH), we propose that Ant can be beneficial to NAFLD, and that the AMPK/Sirt1/PPARγ/SREBP-1c pathways may be involved in such alleviations. To uncover this, we carried out this study with 60 male C57BL/6 mice fed high-fat high-fructose diet (HFD) for 60 days, in order to induce NAFLD/NASH. Mice were then grouped and treated (by oral administration) as: G1: control; G2: HFD (HFD control); G3: Ant, 40 mgkg (Ant control); G4: HFD+Orlistat (10 mg/kg) (as Orlistat control); G5: HFD+Ant L (20 mg/kg); and G6: HFD+Ant H (40 mg/kg) for 45 days. The results indicated Ant at 40 mg/kg effectively suppressed the plasma levels of malondialdehyde, total cholesterol, triglycerides, GOT, GPT, uric acid, glucose, and insulin; upregulated leptin, adiponectin, pAMPK, Sirt1, and down-regulated PPARγ and SREBP-1c. Conclusively, Ant effectively alleviates NAFLD via AMPK/Sirt1/CREBP-1c/PPARγ pathway.

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Barley Sprouts Extract Attenuates Alcoholic Fatty Liver Injury in Mice by Reducing Inflammatory Response

Nutrients ◽

10.3390/nu8070440 ◽

2016 ◽

Vol 8 (7) ◽

pp. 440 ◽

Cited By ~ 14

Author(s):

Yun-Hee Lee ◽

Joung-Hee Kim ◽

Sou Kim ◽

Ji Oh ◽

Woo Seo ◽

...

Keyword(s):

Liver Injury ◽

Inflammatory Response ◽

Fatty Liver ◽

Alcoholic Fatty Liver

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Fatty liver disease in children

10.1093/med/9780198569862.003.0055 ◽

2011 ◽

Author(s):

R. Mark Beattie ◽

Anil Dhawan ◽

John W.L. Puntis

Keyword(s):

Liver Disease ◽

Alcohol Consumption ◽

Liver Injury ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Alcoholic Hepatitis ◽

Alcoholic Fatty Liver ◽

End Stage Liver Disease ◽

End Stage ◽

Alcoholic Fatty Liver Disease

Demographics 406Pathophysiology 406Differential diagnoses 407Presenting features 407Investigation 408Management 409Fatty liver disease is now increasingly recognized in children, particularly in the setting of obesity.The term non-alcoholic steatohepatitis (NASH) was first coined in 1980 by Ludwig to describe a pattern of liver injury in adults in which the liver histology was consistent with alcoholic hepatitis, but in whom significant alcohol consumption was denied. NASH can be considered as part of a broader spectrum of non-alcoholic fatty liver disease that extends from simple steatosis through steatohepatitis that is characterized by the potential to progress to fibrosis, cirrhosis and subsequent end stage liver disease....

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