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.

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 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 Inhibition of miR-499-5p expression improves nonalcoholic fatty liver disease

2019 ◽  
Author(s):  
Hanyun Liu ◽  
Ting Wang ◽  
Xi Chen ◽  
Jing Jiang ◽  
Nianhua Song ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Lentiviral Vector ◽  
Cell Model ◽  
Hepatic Lipid Metabolism ◽  
Nonalcoholic Fatty Liver ◽  
Oil Red O Staining

Abstract Background: Nonalcoholic fatty liver disease (NAFLD) is one of the leading causes of chronic liver diseases. However, the pathogenesis of NAFLD is largely unknown. Here, we investigated the specific role of miR-499-5p in NAFLD. Method: Free fatty acid (FFA) was used to induce HL-7702 cell line to establish a NAFLD cell model, and animal models of NAFLD were constructed by feeding C57BL/6 mice with high fat diet (HFD). Expression levels of miR-499-5p in the HL-7702 cells and C57BL/6 mice were determined by RT-qPCR. In addition, functional experiments were carried out through transfecting miR-499-5p inhibitor into NAFLD cells, and injecting NAFLD mice with a lentiviral vector with knock down the miR-499-5p . Furthermore, the effects of miR-499-5p inhibition on lipidation and inflammation were investigated by oil red O staining, HE staining, and biochemical analysis. Results: Compared with normal controls, the expression of miR-499-5p was significantly up-regulated in NAFLD cells and tissues in mouse (P < 0.05). After NAFLD cells transfected by miR-499-5p inhibitor, the expression of miR-499-5p was inhibited, the lipid deposition and content of TG were reduced, and the lipidation was improved (P < 0.05). Simultaneously, after NAFLD mice were injected with knocked down the miR-499-5p lentiviral vector, the degree of lipid droplet deposition and content of TG were also reduced. Besides, it also decreased the levels of TC and AST in serum, and improved hepatic lipid metabolism (P < 0.05). Conclusion: Inhibition of miR-499-5p expression improved NAFLD in mice, which provided a new direction for the treatment of NAFLD.

scholarly journals Deficiency in Galectin-3 Promotes Hepatic Injury in CDAA Diet-Induced Nonalcoholic Fatty Liver Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Kazuhiro Nomoto ◽  
Takeshi Nishida ◽  
Yuko Nakanishi ◽  
Makoto Fujimoto ◽  
Ichiro Takasaki ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Hepatic Injury ◽  
Inflammatory Responses ◽  
Expression Profiles ◽  
Severe Form ◽  
Nonalcoholic Fatty Liver ◽  
Galectin 3

Nonalcoholic fatty liver disease (NAFLD) is increasingly recognized as a condition in which excess fat accumulates in hepatocytes. Nonalcoholic steatohepatitis (NASH), a severe form of NAFLD in which inflammation and fibrosis in the liver are noted, may eventually progress to end-stage liver disease. Galectin-3, a β-galactoside-binding animal lectin, is a multifunctional protein. This protein is involved in inflammatory responses and carcinogenesis. We investigated whether galectin-3 is involved in the development of NASH by comparing galectin-3 knockout (gal3−/−) mice and wild-type (gal3+/+) mice with choline-deficient L-amino-acid-defined (CDAA) diet-induced NAFLD/NASH. Hepatic injury was significantly more severe in thegal3−/−male mice, as compared to thegal3+/+mice. Data generated by microarray analysis of gene expression suggested that galectin-3 deficiency causes alterations in the expression of various genes associated with carcinogenesis and lipid metabolism. Through canonical pathway analysis, involvement of PDGF and IL-6 signaling pathways was suggested in galectin-3 deficiency. Significant increase of CD14, Fos, and Jun, those that were related to lipopolysaccharide-mediated signaling, was candidate to promote hepatocellular damages in galectin-3 deficiency. In conclusion, galectin-3 deficiency in CDAA diet promotes NAFLD features. It may be caused by alterations in the expression profiles of various hepatic genes including lipopolysaccharide-mediated inflammation.

scholarly journals Hepatic gene expression profiles differentiate presymptomatic patients with mild versus severe nonalcoholic fatty liver disease

Hepatology ◽  
2013 ◽  
Vol 59 (2) ◽  
pp. 471-482 ◽  
Author(s):  
Cynthia A. Moylan ◽  
Herbert Pang ◽  
Andrew Dellinger ◽  
Ayako Suzuki ◽  
Melanie E. Garrett ◽  
...  
Keyword(s):  
Gene Expression ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Hepatic Gene Expression ◽  
Nonalcoholic Fatty Liver

scholarly journals MicroRNAs in Nonalcoholic Fatty Liver Disease: Novel Biomarkers and Prognostic Tools during the Transition from Steatosis to Hepatocarcinoma

2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Manuele Gori ◽  
Mario Arciello ◽  
Clara Balsano
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Malignant Tumors ◽  
Current Knowledge ◽  
Expression Profiles ◽  
Therapeutic Interventions ◽  
Related Disorder ◽  
Nonalcoholic Fatty Liver

Nonalcoholic fatty liver disease (NAFLD) is a metabolic-related disorder ranging from steatosis to steatohepatitis, which may progress to cirrhosis and hepatocellular carcinoma (HCC). The influence of NAFLD on HCC development has drawn attention in recent years. HCC is one of the most common malignant tumors and the third highest cause of cancer-related death. HCC is frequently diagnosed late in the disease course, and patient’s prognosis is usually poor. Early diagnosis and identification of the correct stage of liver damage during NAFLD progression can contribute to more effective therapeutic interventions, improving patient outcomes. Therefore, scientists are always searching for new sensitive and reliable markers that could be analysed through minimally invasive tests. MicroRNAs are short noncoding RNAs that act as posttranscriptional regulators of gene expression. Several studies identified specific miRNA expression profiles associated to different histological features of NAFLD. Thus, miRNAs are receiving growing attention as useful noninvasive diagnostic markers to follow the progression of NAFLD and to identify novel therapeutic targets. This review focuses on the current knowledge of the miRNAs involved in NAFLD and related HCC development, highlighting their diagnostic and prognostic value for the screening of NAFLD patients.

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