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 Role of Docosahexaenoic Acid Treatment in Improving Liver Histology in Pediatric Nonalcoholic Fatty Liver Disease

PLoS ONE ◽  
2014 ◽  
Vol 9 (2) ◽  
pp. e88005 ◽  
Author(s):  
Valerio Nobili ◽  
Guido Carpino ◽  
Anna Alisi ◽  
Rita De Vito ◽  
Antonio Franchitto ◽  
...  
Keyword(s):  
Liver Disease ◽  
Docosahexaenoic Acid ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Acid Treatment ◽  
Liver Histology ◽  
Nonalcoholic Fatty Liver

scholarly journals Role of folate in nonalcoholic fatty liver disease

2017 ◽  
Vol 95 (10) ◽  
pp. 1141-1148 ◽  
Author(s):  
Victoria Sid ◽  
Yaw L. Siow ◽  
Karmin O
Keyword(s):  
Type 2 Diabetes ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Serum Folate ◽  
Nonalcoholic Fatty Liver ◽  
Obesity And Diabetes

Nonalcoholic fatty liver disease (NAFLD) is a spectrum of chronic liver conditions that are characterized by steatosis, inflammation, fibrosis, and liver injury. The global prevalence of NAFLD is rapidly increasing in proportion to the rising incidence of obesity and type 2 diabetes. Because NAFLD is a multifaceted disorder with many underlying metabolic abnormalities, currently, there is no pharmacological agent that is therapeutically approved for the treatment of this disease. Folate is a water-soluble B vitamin that plays an essential role in one-carbon transfer reactions involved in nucleic acid biosynthesis, methylation reactions, and sulfur-containing amino acid metabolism. The liver is the primary organ responsible for storage and metabolism of folates. Low serum folate levels have been observed in patients with obesity and diabetes. It has been reported that a low level of endogenous folates in rodents perturbs folate-dependent one-carbon metabolism, and may be associated with development of metabolic diseases such as NAFLD. This review highlights the biological role of folate in the progression of NAFLD and its associated metabolic complications including obesity and type 2 diabetes. Understanding the role of folate in metabolic disease may position this vitamin as a potential therapeutic for NAFLD.

scholarly journals Efficacy of Ursodeoxycholic Acid in Nonalcoholic Fatty Liver Disease: An Updated Meta-Analysis of Randomized Controlled Trials

2019 ◽  
Author(s):  
Wenyue Zhang ◽  
Yao Tang ◽  
Juan Huang ◽  
Hong Ren ◽  
Yixuan Yang ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Ursodeoxycholic Acid ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Total Bilirubin ◽  
Meta Analysis ◽  
Nonalcoholic Fatty Liver ◽  
Randomized Controlled

Abstract Background Nonalcoholic fatty liver disease (NAFLD) is a kind of chronic liver disease among general population. Recent years, more and more new experiments have made the role of ursodeoxycholic acid (UDCA) become clearer. In this meta-analysis, we analyzed the efficacy of ursodeoxycholic acid (UDCA) for the treatment of nonalcoholic fatty liver disease (NAFLD). Methods We searched the Web of Science, Pubmed, Embase and Cochrane library databases for relavent studies published before March 1, 2019. We examined 134 randomized controlled trials (RCTs) that investigated the effectiveness of UDCA in NAFLD against placebo or other treatments. Next, we conducted meta-analysis by Stata(version 12.0) to examine the change among several indices: Alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), Alkaline phosphatase (AP), total bilirubin and albumin. Results Following the application of different inclusion and exclusion criteria, 9 articles with 1106 participants were finally selected. The forest plot displayed that UDCA treatment can significantly decrease the ALT levels among the NAFLD patients (SMD=0.17,95%CI [0.03 to 0.3], P=0.07). However, UDCA treatment did not significantly affect the AST, GGT, AP, total bilirubin and albumin levels. Further, the subgroup analyses suggested the significant role of UDCA treatment in different geographical regions, age group and treatment duration (P=0.003 in people from Europe, P=0.001 in people older than 50 years and P=0.008 in longer duration(>6 months)). Conclusion In this study, several indices we analyzed among 9 articles. UDCA treatment was found beneficial in lowering the ALT levels in NAFLD patients. The remaining indices like AST, GGT, AP showed non-significant changes in this analysis. This could be attributed for the insufficient number of trials because all parameters were not analyzed in each individual RCT. Therefore, future meta-analysis will be required to fully confirm and validate the efficacy of UDCA in NAFL.

scholarly journals Role of insulin resistance in the pathogenesis of nonalcoholic fatty liver disease

2010 ◽  
Vol 18 (30) ◽  
pp. 3175
Author(s):  
Bing-Fang Wang ◽  
Pei-Ying Tian ◽  
Kun Feng ◽  
Fu-Rong Wu ◽  
Yong-Gao Lu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Nonalcoholic Fatty Liver

scholarly journals Role of Bile Acids in Dysbiosis and Treatment of Nonalcoholic Fatty Liver Disease

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Caihua Wang ◽  
Chunpeng Zhu ◽  
Liming Shao ◽  
Jun Ye ◽  
Yimin Shen ◽  
...  
Keyword(s):  
Liver Disease ◽  
Bile Acid ◽  
Gut Microbiota ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Bile Acids ◽  
Fatty Liver Disease ◽  
Nonalcoholic Fatty Liver ◽  
Bile Acid Receptors

Nonalcoholic fatty liver disease (NAFLD) is a major health threat around the world and is characterized by dysbiosis. Primary bile acids are synthesized in the liver and converted into secondary bile acids by gut microbiota. Recent studies support the role of bile acids in modulating dysbiosis and NAFLD, while the mechanisms are not well elucidated. Dysbiosis may alter the size and the composition of the bile acid pool, resulting in reduced signaling of bile acid receptors such as farnesoid X receptor (FXR) and Takeda G protein-coupled receptor 5 (TGR5). These receptors are essential in lipid and glucose metabolism, and impaired bile acid signaling may cause NAFLD. Bile acids also reciprocally regulate the gut microbiota directly via antibacterial activity and indirectly via FXR. Therefore, bile acid signaling is closely linked to dysbiosis and NAFLD. During the past decade, stimulation of bile acid receptors with their agonists has been extensively explored for the treatment of NAFLD in both animal models and clinical trials. Early evidence has suggested the potential of bile acid receptor agonists in NAFLD management, but their long-term safety and effectiveness need further clarification.

scholarly journals The Role of Probiotics in Nonalcoholic Fatty Liver Disease: A New Insight into Therapeutic Strategies

Nutrients ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 2642 ◽  
Author(s):  
Marica Meroni ◽  
Miriam Longo ◽  
Paola Dongiovanni
Keyword(s):  
Liver Disease ◽  
Gut Microbiota ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Bacterial Overgrowth ◽  
Therapeutic Interventions ◽  
Mucosal Inflammation ◽  
Nonalcoholic Fatty Liver

Nonalcoholic fatty liver disease (NAFLD) encompasses a broad spectrum of pathological hepatic conditions ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), which may predispose to liver cirrhosis and hepatocellular carcinoma (HCC). Due to the epidemic obesity, NAFLD is representing a global health issue and the leading cause of liver damage worldwide. The pathogenesis of NAFLD is closely related to insulin resistance (IR), adiposity and physical inactivity as well as genetic and epigenetic factors corroborate to the development and progression of hepatic steatosis and liver injury. Emerging evidence has outlined the implication of gut microbiota and gut-derived endotoxins as actively contributors to NAFLD pathophysiology probably due to the tight anatomo-functional crosstalk between the gut and the liver. Obesity, nutrition and environmental factors might alter intestinal permeability producing a favorable micro-environment for bacterial overgrowth, mucosal inflammation and translocation of both invasive pathogens and harmful byproducts, which, in turn, influence hepatic fat composition and exacerbated pro-inflammatory and fibrotic processes. To date, no therapeutic interventions are available for NAFLD prevention and management, except for modifications in lifestyle, diet and physical exercise even though they show discouraging results due to the poor compliance of patients. The premise of this review is to discuss the role of gut–liver axis in NAFLD and emphasize the beneficial effects of probiotics on gut microbiota composition as a novel attractive therapeutic strategy to introduce in clinical practice.

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