Exosomal miRNAs Profile in Children’s Nonalcoholic Fatty Liver Disease and the Correlation with Transaminase and Uric Acid

2020 ◽  
Vol 76 (1) ◽  
pp. 44-53 ◽  
Author(s):  
Xuelian Zhou ◽  
Ke Huang ◽  
Junjun Jia ◽  
Yan Ni ◽  
Jinna Yuan ◽  
...  

Objective: The incidence of non-alcoholic fatty liver disease (NAFLD) in children increased rapidly. However, the pathogenesis of NAFLD, especially how non-alcoholic fatty liver progress to non-alcoholic steatohepatitis, is still unclear. This study aims to explore the exosomal miRNAs profiles and the underline pathogenesis of child NAFLD. Methods: Twenty NAFLD and 20 health control were enrolled in this study. Circulating exosomes were isolated, and RNA sequencing was performed in test set (3 NAFLD/3 Controls). The differentially expressed miRNAs (DEM) were further validated in validation set (17 NAFLD/17 Controls). Spearman correlation ­analysis was used to investigate the association between DEM and clinical parameters. Results: Eighty-two miRNAs were differentially expressed (absolute fold change >2 and p < 0.05) in the 2 groups, they were involved in fat acid metabolism, starch and sucrose metabolism, bile acid metabolism and inflammation. miRNA122-5p, miRNA34a-5p, ­miRNA155-5p and miRNA146b-3p were up-regulated in NAFLD group (p < 0.05) and positively correlated with body mass index (r, 0.41–0.59), alanine aminotransferase (r, 0.36–0.52), aspartate transaminase (r, 0.31–0.48) and uric acid (UA, r, 0.51–0.69; p < 0.05). Conclusions: Circulating exosomal miRNAs may be involved in the pathogenesis of NAFLD and correlated with transaminase and UA.

2021 ◽  
Vol 22 (22) ◽  
pp. 12431
Author(s):  
Russell R. Fling ◽  
Timothy R. Zacharewski

Gut dysbiosis with disrupted enterohepatic bile acid metabolism is commonly associated with non-alcoholic fatty liver disease (NAFLD) and recapitulated in a NAFLD-phenotype elicited by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in mice. TCDD induces hepatic fat accumulation and increases levels of secondary bile acids, including taurolithocholic acid and deoxycholic acid (microbial modified bile acids involved in host bile acid regulation signaling pathways). To investigate the effects of TCDD on the gut microbiota, the cecum contents of male C57BL/6 mice orally gavaged with sesame oil vehicle or 0.3, 3, or 30 µg/kg TCDD were examined using shotgun metagenomic sequencing. Taxonomic analysis identified dose-dependent increases in Lactobacillus species (i.e., Lactobacillus reuteri). Increased species were also associated with dose-dependent increases in bile salt hydrolase sequences, responsible for deconjugation reactions in secondary bile acid metabolism. Increased L. reuteri levels were further associated with mevalonate-dependent isopentenyl diphosphate (IPP) biosynthesis and o-succinylbenzoate synthase, a menaquinone biosynthesis associated gene. Analysis of the gut microbiomes from cirrhosis patients identified an increased abundance of genes from the mevalonate-dependent IPP biosynthesis as well as several other menaquinone biosynthesis genes, including o-succinylbenzoate synthase. These results extend the association of lactobacilli with the AhR/intestinal axis in NAFLD progression and highlight the similarities between TCDD-elicited phenotypes in mice to human NAFLD.


2018 ◽  
Vol 1 (2) ◽  
pp. 24-28
Author(s):  
Tanita Suttichaimongkol

Non-alcoholic fatty liver disease (NAFLD) is a leading cause of death from liver cirrhosis, endstage liver disease, and hepatocellular carcinoma. It is also associated with increased cardiovasculardisease and cancer related mortality. While lifestyle modifications are the mainstay of treatment,only a proportion of patients are able to make due to difficult to achieve and maintain, and so moretreatment options are required such as pharmacotherapy. This review presents the drugs used inmanaging NAFLD and their pharmacologic targets. Therapies are currently directed towards improvingthe metabolic status of the liver, insulin resistance, cell oxidative stress, apoptosis, inflammation orfibrosis. Several agents are now in large clinical trials and within the next few years, the availability oftherapeutic options for NAFLD will be approved.     Keywords: nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, fibrosis, cirrhosis  


2020 ◽  
Vol 21 (6) ◽  
pp. 599-609 ◽  
Author(s):  
Longxin Qiu ◽  
Chang Guo

Aldose reductase (AR) has been reported to be involved in the development of nonalcoholic fatty liver disease (NAFLD). Hepatic AR is induced under hyperglycemia condition and converts excess glucose to lipogenic fructose, which contributes in part to the accumulation of fat in the liver cells of diabetes rodents. In addition, the hyperglycemia-induced AR or nutrition-induced AR causes suppression of the transcriptional activity of peroxisome proliferator-activated receptor (PPAR) α and reduced lipolysis in the liver, which also contribute to the development of NAFLD. Moreover, AR induction in non-alcoholic steatohepatitis (NASH) may aggravate oxidative stress and the expression of inflammatory cytokines in the liver. Here, we summarize the knowledge on AR inhibitors of plant origin and review the effect of some plant-derived AR inhibitors on NAFLD/NASH in rodents. Natural AR inhibitors may improve NAFLD at least in part through attenuating oxidative stress and inflammatory cytokine expression. Some of the natural AR inhibitors have been reported to attenuate hepatic steatosis through the regulation of PPARα-mediated fatty acid oxidation. In this review, we propose that the natural AR inhibitors are potential therapeutic agents for NAFLD.


2018 ◽  
Vol 16 (3) ◽  
pp. 269-275 ◽  
Author(s):  
Paschalis Paschos ◽  
Vasilios G. Athyros ◽  
Achilleas Tsimperidis ◽  
Anastasia Katsoula ◽  
Nikolaos Grammatikos ◽  
...  

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