scholarly journals Si-Wu-Tang Alleviates Nonalcoholic Fatty Liver Disease via Blocking TLR4-JNK and Caspase-8-GSDMD Signaling Pathways

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Yaxing Zhang ◽  
Ge Zhou ◽  
Zifeng Chen ◽  
Weibing Guan ◽  
Jiongshan Zhang ◽  
...  
Keyword(s):  
Body Weight ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Signaling Pathways ◽  
Fatty Liver Disease ◽  
Caspase 8 ◽  
Nonalcoholic Fatty Liver ◽  
Oil Red O Staining ◽  
Oil Red O

Background. Nonalcoholic fatty liver disease (NAFLD) has high global prevalence; however, the treatments of NAFLD are limited due to lack of approved drugs. Methods. Mice were randomly assigned into three groups: Control group, NAFLD group, NAFLD plus Si-Wu-Tang group. A NAFLD mice model was established by feeding with a methionine- and choline-deficient (MCD) diet for four weeks. Si-Wu-Tang was given orally by gastric gavage at the beginning of 3rd week, and it lasted for two weeks. The treatment effects of Si-Wu-Tang were confirmed by examining the change of body weight, serum alanine aminotransferase (ALT) and aspartate transaminase (AST) levels, Oil Red O staining, and hematoxylin and eosin (H&E) staining of the liver samples and accompanied by steatosis grade scores. The expression and activation of the possible signaling proteins involved in the pathogenesis of NAFLD were determined by western blotting. Results. Mice fed with four weeks of MCD diet displayed elevated serum levels of ALT and AST, while there was decreased body weight. The hepatic Oil Red O staining and H&E staining showed severe liver steatosis with high steatosis grade scores. All these can be improved by treating with Si-Wu-Tang for two weeks. Mechanistically, the increased hepatic TLR4 expression and its downstream JNK phosphorylation induced by MCD diet were suppressed by Si-Wu-Tang. Moreover, the upregulations of Caspase-8, gasdermin D (GSDMD), and cleaved-GSDMD in liver mediated by MCD diet were all inhibited by Si-Wu-Tang. Conclusions. Treatment with Si-Wu-Tang improves MCD diet-induced NAFLD in part via blocking TLR4-JNK and Caspase-8-GSDMD signaling pathways, suggesting that Si-Wu-Tang has potential for clinical application in treating NAFLD.

scholarly journals The role and possible mechanism of the long noncoding RNA LINC01260 in nonalcoholic fatty liver disease

2022 ◽  
Vol 19 (1) ◽  
Author(s):  
Xiaoxiao Ge ◽  
Tao Sun ◽  
Yanmei Zhang ◽  
Yongqing Li ◽  
Peng Gao ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Differential Expression ◽  
Fatty Liver Disease ◽  
Lipid Droplets ◽  
Expression Profiles ◽  
Nonalcoholic Fatty Liver ◽  
Oil Red O Staining ◽  
Oil Red O

Abstract Objective To investigate the differential expression profile of lncRNAs in the nonalcoholic fatty liver disease (NAFLD) model induced by oleic acid (OA) and to further explore the role of LINC01260 (ENST00000255183) in NAFLD, providing theoretical support for the clinical value of lncRNAs in NAFLD. Methods OA (50 μg/mL) was used to induce steatosis in normal human LO2 hepatocytes for 48 h and was verified by Oil red O staining. Differential expression profiles of lncRNAs were obtained by eukaryotic circular sequencing (RNA/lncRNA/circRNA-seq) techniques. A gain-of-function (GOF) strategy for LINC01260 was adopted, Oil red O staining and semiquantitative analysis were combined to explore whether the GOF of LINC01260 affects LO2 cell steatosis. CeRNA-based bioinformatics analysis of lncRNAs was performed, and the enriched mRNAs were further verified. RXRB siRNAs were applied and verify its role in LINC01260 regulated OA-induced hepatocytes steatosis. Results Lipid droplets of different sizes were observed in the cells of the OA group. Absorbance in the OA group was significantly increased after isopropanol decolorization (P < 0.05). Compared with those in the control group, there were 648 lncRNAs with differential expression greater than 1 time in the OA group, of which 351 were upregulated and 297 were downregulated. Fluorescence quantitative PCR showed that the expression of LINC01260 in the OA group was downregulated by 0.35 ± 0.07-fold (P < 0.05). The formation of lipid droplets in LO2 cells of the LINC01260 GOF group decreased significantly (P < 0.05). CeRNA analysis indicated that the mRNA levels of RXRB, RNPEPL1, CD82, MADD and KLC2 were changed to different degrees. Overexpression of LINC01260 significantly induced RXRB transcription (P < 0.05) and translation, and RXRB silence attenuated the lipids decrease induced by LINC01260 overexpression. Conclusion The OA-induced NAFLD cell model has a wide range of lncRNA differential expression profiles. LINC01260 participates in the regulation of the lipid droplet formation process of NAFLD, and its overexpression can significantly inhibit the steatosis process of LO2 cells. Mechanistically, LINC01260 may act as a ceRNA to regulate the expression of RXRB, thereby affecting the adipocytokine signaling pathway.

Onset of Ulcerative Colitis in a Patient with Nonalcoholic Fatty Liver Disease (NAFLD): Dramatic Effect of Plant-based Diet for NAFLD

2019 ◽  
Vol 25 (11) ◽  
pp. e146-e147 ◽  
Author(s):  
Mitsuro Chiba ◽  
Kunio Nakane ◽  
Hitoshi Abe ◽  
Masafumi Komatsu ◽  
Haruhiko Tozawa
Keyword(s):  
Ulcerative Colitis ◽  
Metabolic Syndrome ◽  
Weight Loss ◽  
Body Weight ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Nonalcoholic Fatty Liver ◽  
Normal Ranges

Abstract Nonalcoholic fatty liver disease (NAFLD) develops in ulcerative colitis (UC) and Crohn’s disease. However, there is scarce reporting on the onset of UC in patients with NAFLD. A 44-year-old man was diagnosed with UC and referred to us in 2019. His height was 166.0 cm, and body weight was 86.3 kg. The waist circumference was 93.7 cm (normal range <85) and triglyceride was 751 mg/dL. These findings, in addition to hypertension, resulted in a diagnosis of metabolic syndrome. HbA1c was normal. Ultrasonography disclosed severe fatty liver. Nonalcoholic fatty liver disease was diagnosed. He underwent 12 days of educational hospitalization for UC. A lacto-ovo-semi-vegetarian diet (1400 kcal/day), a kind of plant-based diet (PBD), was provided. He lost 4 kg, which was 4.6% of his base body weight. Triglyceride and total cholesterol decreased to the normal ranges. Transaminases and γ-glutamyl transpeptidase also decreased. His body weight decreased further after discharge. Follow-up ultrasonography indicated an improvement in hepatic enlargement. The shear wave velocity decreased from 1.11 to 0.88 m/s. His soft stool became normal stool by 2 months after discharge. Records of his health checkups revealed the presence of metabolic syndrome and abnormal liver function tests already in 2015. Thus, it was concluded that UC developed in a patient with NAFLD in this case. Plant-based diet has already been shown to be effective in inflammatory bowel disease (IBD). In the present case, NAFLD parameters were dramatically improved by PBD. Whether the improvement was due to weight loss per se or due to weight loss with PBD is to be clarified.

scholarly journals Ameliorative Potential ofTamarindus indicaon High Fat Diet Induced Nonalcoholic Fatty Liver Disease in Rats

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Suja Rani Sasidharan ◽  
Joshua Allan Joseph ◽  
Senthilkumar Anandakumar ◽  
Vijayabalaji Venkatesan ◽  
Chandrasekharan Nair Ariyattu Madhavan ◽  
...  
Keyword(s):  
Body Weight ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
High Fat Diet ◽  
Fatty Liver Disease ◽  
Resistance Index ◽  
High Fat ◽  
Nonalcoholic Fatty Liver ◽  
Dose Levels

Nonalcoholic fatty liver disease (NAFLD), the prevalence of which is rising globally with current upsurge in obesity, is one of the most frequent causes of chronic liver diseases. The present study evaluated the ameliorative effect of extract ofTamarindus indicaseed coat (ETS) on high fat diet (HFD) induced NAFLD, after daily administration at 45, 90, and 180 mg/kg body weight dose levels for a period of 6 weeks, in albino Wistar rats. Treatment with ETS at all tested dose levels significantly attenuated the pathological alterations associated with HFD induced NAFLDviz. hepatomegaly, elevated hepatic lipid and lipid peroxides, serum alanine aminotransferase, and free fatty acid levels as well as micro-/macrohepatic steatosis. Moreover, extract treatment markedly reduced body weight and adiposity along with an improvement in insulin resistance index. The study findings, therefore suggested the therapeutic potential of ETS against NAFLD, acting in part through antiobesity, insulin sensitizing, and antioxidant mechanisms.

scholarly journals Exenatide Delays the Progression of Nonalcoholic Fatty Liver Disease in C57BL/6 Mice, Which May Involve Inhibition of the NLRP3 Inflammasome through the Mitophagy Pathway

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Ning Shao ◽  
Xin-Yang Yu ◽  
Xue-Fei Ma ◽  
Wen-Jian Lin ◽  
Ming Hao ◽  
...  
Keyword(s):  
Body Weight ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Nlrp3 Inflammasome ◽  
Fatty Liver Disease ◽  
The Body ◽  
Control Group ◽  
Stress Injury ◽  
Nonalcoholic Fatty Liver

Objective. This study is aimed at investigating whether exenatide (Exe) delays the progression of nonalcoholic fatty liver disease (NAFLD) in C57BL/6 mice by targeting the NLRP3 inflammasome through the autophagy/mitophagy pathway. Methods. Thirty male C57BL/6 mice were randomly divided into three groups: control group (n=10), model group (n=10), and Exe (exenatide) group (n=10). Mouse models of NAFLD and diabetes were established using a high-fat diet and streptozocin. Results. The levels of fasting blood glucose (FBG), total cholesterol (TC), and triglyceride (TG) in the serum were significantly reduced after Exe treatment. The body weight, liver weight/body weight, and number of lipid droplets in the liver significantly decreased in Exe-treated mice. Treatment with Exe markedly reduced the levels of liver lipids, malondialdehyde (MDA), and alanine aminotransferase (ALT) in serum and livers. The number of autophagosomes increased significantly in the Exe group. The expression of LC3A/B-II/I, Beclin-1, Parkin, and BNIP3L increased significantly, whereas NLRP3 and IL-1β proteins were suppressed after Exe treatment. Conclusion. We successfully established a mouse model of NAFLD and diabetes. Exe may reduce oxidative stress injury and inhibit the NLRP3 inflammasome by enhancing the autophagy/mitophagy pathway in liver, which has a protective effect on the liver in NAFLD and diabetes in C57BL/6 mice.

scholarly journals Bile Acid Receptors and the Gut–Liver Axis in Nonalcoholic Fatty Liver Disease

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 2806
Author(s):  
Rui Xue ◽  
Lianyong Su ◽  
Shengyi Lai ◽  
Yanyan Wang ◽  
Derrick Zhao ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Signaling Pathways ◽  
Disease Progression ◽  
Fatty Liver Disease ◽  
Current Understanding ◽  
Nonalcoholic Fatty Liver ◽  
Therapeutic Implications ◽  
Global Epidemic

The prevalence of nonalcoholic fatty liver disease (NAFLD) has been significantly increased due to the global epidemic of obesity. The disease progression from simple steatosis (NAFL) to nonalcoholic steatohepatitis (NASH) is closely linked to inflammation, insulin resistance, and dysbiosis. Although extensive efforts have been aimed at elucidating the pathological mechanisms of NAFLD disease progression, current understanding remains incomplete, and no effective therapy is available. Bile acids (BAs) are not only important physiological detergents for the absorption of lipid-soluble nutrients in the intestine but also metabolic regulators. During the last two decades, BAs have been identified as important signaling molecules involved in lipid, glucose, and energy metabolism. Dysregulation of BA homeostasis has been associated with NAFLD disease severity. Identification of nuclear receptors and G-protein-coupled receptors activated by different BAs not only significantly expanded the current understanding of NAFLD/NASH disease progression but also provided the opportunity to develop potential therapeutics for NAFLD/NASH. In this review, we will summarize the recent studies with a focus on BA-mediated signaling pathways in NAFLD/NASH. Furthermore, the therapeutic implications of targeting BA-mediated signaling pathways for NAFLD will also be discussed.

scholarly journals Nonalcoholic Fatty Liver Disease: Pathogenesis and Therapeutics from a Mitochondria-Centric Perspective

2014 ◽  
Vol 2014 ◽  
pp. 1-20 ◽  
Author(s):  
Aaron M. Gusdon ◽  
Ke-xiu Song ◽  
Shen Qu
Keyword(s):  
Lipid Metabolism ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Signaling Pathways ◽  
Fatty Liver Disease ◽  
Beta Oxidation ◽  
Hepatic Lipid Metabolism ◽  
Nonalcoholic Fatty Liver ◽  
Hepatic Lipid

Nonalcoholic fatty liver disease (NAFLD) describes a spectrum of disorders characterized by the accumulation of triglycerides within the liver. The global prevalence of NAFLD has been increasing as the obesity epidemic shows no sign of relenting. Mitochondria play a central role in hepatic lipid metabolism and also are affected by upstream signaling pathways involved in hepatic metabolism. This review will focus on the role of mitochondria in the pathophysiology of NAFLD and touch on some of the therapeutic approaches targeting mitochondria as well as metabolically important signaling pathways. Mitochondria are able to adapt to lipid accumulation in hepatocytes by increasing rates of beta-oxidation; however increased substrate delivery to the mitochondrial electron transport chain (ETC) leads to increased reactive oxygen species (ROS) production and eventually ETC dysfunction. Decreased ETC function combined with increased rates of fatty acid beta-oxidation leads to the accumulation of incomplete products of beta-oxidation, which combined with increased levels of ROS contribute to insulin resistance. Several related signaling pathways, nuclear receptors, and transcription factors also regulate hepatic lipid metabolism, many of which are redox sensitive and regulated by ROS.

Effect of changes on body weight and lifestyle in nonalcoholic fatty liver disease

2005 ◽  
Vol 43 (6) ◽  
pp. 1060-1066 ◽  
Author(s):  
Ayako Suzuki ◽  
Keith Lindor ◽  
Jenny St Saver ◽  
James Lymp ◽  
Flavia Mendes ◽  
...  
Keyword(s):  
Body Weight ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Nonalcoholic Fatty Liver
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