scholarly journals Serum miR-379 expression is related to the development and progression of hypercholesterolemia in non-alcoholic fatty liver disease

2019 ◽  
Author(s):  
Kinya Okamoto ◽  
Masahiko Koda ◽  
Toshiaki Okamoto ◽  
Takumi Onoyama ◽  
Kenichi Miyoshi ◽  
...  

AbstractIntroductionNon-alcoholic fatty liver disease (NAFLD) has a wide spectrum, eventually leading to cirrhosis and hepatic carcinogenesis. We previously reported that a series of microRNAs (miRNAs) mapped in the 14q32.2 maternally imprinted gene region (Dlk1-Dio3 mat) are related to NAFLD development and progression in a mouse model. We examined the suitability of miR-379, a circulating Dlk1-Dio3 mat miRNA, as a human NAFLD biomarker.MethodsEighty NAFLD patients were recruited for this study. miR-379 was selected from the putative Dlk1-Dio3 mat miRNA cluster because it exhibited the greatest expression difference between NAFLD and non-alcoholic steatohepatitis in our preliminary study. Real-time PCR was used to examine the expression levels of miR-379 and miR-16 as an internal control.ResultsCompared to normal controls, serum miR-379 expression was significantly up-regulated in NAFLD patients. Receiver operating characteristic curve analysis suggested that miR-379 is a suitable marker for discriminating NAFLD patients from controls, with an area under the curve value of 0.72. Serum miR-379 exhibited positive correlations with alkaline phosphatase, total cholesterol, and low-density-lipoprotein cholesterol levels in patients with early stage NAFLD (Brunt fibrosis stage 0 to 1). The correlation between serum miR-379 and cholesterol levels was lost in early stage NAFLD patients treated with statins. Software-based predictions indicated that various energy metabolism–related genes, including insulin-like growth factor-1 (IGF-1) and IGF-1 receptor, are potential targets of miR-379.ConclusionsSerum miR-379 exhibits high potential as a biomarker for NAFLD. miR-379 appears to increase cholesterol lipotoxicity, leading to the development and progression of NAFLD, via interference with the expression of target genes, including those related to the IGF-1 signaling pathway. Our results could facilitate future research into the pathogenesis, diagnosis, and treatment of NAFLD.

2021 ◽  
Vol 116 (1) ◽  
pp. S519-S520
Author(s):  
Shilpa Junna ◽  
Malini Chauhan ◽  
Michael Bonelli ◽  
Zachary Warner ◽  
Mark Borgstrom ◽  
...  

2021 ◽  
Vol 8 ◽  
Author(s):  
Ruina Zhai ◽  
Lei Feng ◽  
Yu Zhang ◽  
Wei Liu ◽  
Shengli Li ◽  
...  

Non-alcoholic fatty liver disease develops from simple steatosis to non-alcoholic steatohepatitis (NASH), which then potentially develops into liver cirrhosis. It is a serious threat to human health. Therefore, investigating the formation and development mechanism of non-alcoholic fatty liver disease (NAFLD) is of great significance. Herein, an early model of NAFLD was successfully established by feeding rats with a high-fat and choline-deficient diet. Liver tissue samples were obtained from rats in the fatty liver model group (NAFL) and normal diet control group (CON). Afterward, transcriptome and lipidomic analysis was performed. Transcriptome results revealed that 178 differentially expressed genes were detected in NAFL and CON groups. Out of which, 105 genes were up-regulated, 73 genes were downregulated, and 8 pathways were significantly enriched. A total of 982 metabolites were detected in lipidomic analysis. Out of which 474 metabolites were significantly different, 273 were up-regulated, 201 were downregulated, and 7 pathways were significantly enriched. Based on the joint analysis, 3 common enrichment pathways were found, including cholesterol metabolism and fat digestion and absorption metabolic pathways. Overall, in the early stage of NAFLD, a small number of genetic changes caused a strong response to lipid components. The strongest reflection was glycerides and glycerophospholipids. A significant increase in fatty acid uptake accompanied by cholesterol metabolism is the most prominent metabolic feature of the liver in the early stage of NAFLD. In the early stage of fatty liver, the liver had shown the characteristics of NASH.


2021 ◽  
Vol 15 (8) ◽  
pp. 1776-1781
Author(s):  
Shakila Andlib ◽  
Muhammad Nawaz Anjum ◽  
Faiza Farooq ◽  
Syed Amir Gilani ◽  
Junaid Arshad

Aim: To explore data on non alcoholic fatty liver disease. For this systematic review, our major purpose is to compare grading of fatty liver disease diagnosed on ultrasound with cholesterol level and liver enzymes. Methodology: For this study, total 25 studies were included which follow the Preferred Reporting Items guideline for conducting this systematic review analysis (PRISMA). We search electronic articles from year 2008 to from year 2020 on PUB Med, online Willey library, and ScienceDirect site by using keywords related to sonographic imaging for fatty liver disease. Results: These case studies shows that increasing grades of fatty liver disease are significantly associated with increasing value of total cholesterol levels and liver enzymes.Comparing the heterogeneity level of studies we observed that AST studies have 85% heterogeneity whereas 77% ALT data and 76% GGT data were similar to each other. On the other hand, we observed complete study 12 studies provide information related to TG, TC, HDL, and LDL respectively. Conclusion: Our meta-analysis concluded that the severe cases of liver diseases need biopsies and histopathological examination. Though ultrasonography provides a complete liver picture with 84.8% sensitivity and 93.6% specificity which may help in many cases still the majority of the studies failed to observe steatosis, NAS score. Keywords: Non alcoholic fatty liver disease(NAFLD),ultra sonography,lipid profile ,liver enzymes.


2019 ◽  
Vol 11 (6) ◽  
pp. 478-483
Author(s):  
Meaghan Phipps ◽  
Julia Wattacheril

Individuals with non-alcoholic fatty liver disease (NAFLD) who lack classical risk factors also have the ability to develop nonalcoholic steatohepatitis (NASH) and progression to more advanced liver disease. The pathophysiology and risk factors for the development of NAFLD in non-obese persons are not fully understood but seem to be closely related to insulin resistance, atherogenic dyslipidaemia and alterations in body composition, with some patients harbouring predisposing genetic polymorphisms. In normal-weight individuals, also called ‘lean’, there is limited potential for effective lifestyle change in disease management. Additionally, biological mechanisms underlying the development of NASH in non-obese individuals may reveal novel targets for intervention. In this review, the authors discuss the clinical, histological and genetic features and risk factors for non-obese NAFLD and highlight gaps in knowledge and areas for future research.


JHEP Reports ◽  
2020 ◽  
Vol 2 (6) ◽  
pp. 100150 ◽  
Author(s):  
Justin Chin ◽  
Trevor A. Mori ◽  
Leon A. Adams ◽  
Lawrence J. Beilin ◽  
Rae-Chi Huang ◽  
...  

2019 ◽  
Vol 3 ◽  
pp. 166 ◽  
Author(s):  
April Hartley ◽  
Diana L. Santos Ferreira ◽  
Emma L. Anderson ◽  
Debbie A. Lawlor

Background: Adolescent non-alcoholic fatty liver disease (NAFLD) is associated with cardiometabolic risk factors. The association between adolescent NAFLD and a wide range of metabolic biomarkers is unclear. We have attempted to determine the differences in metabolic profile of adolescents with and without markers of NAFLD. Methods: We performed cross-sectional analyses in a sample of 3,048 participants from the Avon Longitudinal Study of Parents and Children at age 17. We used three indicators of NAFLD: ALT >40 U/l; AST >40 U/l and ultrasound scan-assessed steatosis. Associations between each measure of NAFLD and 154 metabolic traits, assessed by Nuclear Magnetic Resonance, were analyzed by multivariable linear regression, adjusting for age, sex and BMI. Results: All three indicators of NAFLD were associated with ~0.5 standard deviation (SD) greater concentrations of all extremely large to small very low-density lipoproteins (VLDL) measures. ALT >40U/l was associated with ~0.5SD greater concentrations of very small VLDLs, intermediate-density lipoproteins and low-density lipoproteins. Concentrations of most cholesterols, including remnant cholesterol, all triglycerides and monounsaturated fatty acids, in addition to glycoprotein acetyls (inflammatory marker), were also higher in participants with NAFLD. Conclusions: We have identified differing metabolic profiles between adolescents with and without indicators of NAFLD. These results provide the foundations for future research to determine whether these differences persist and result in adverse future cardiometabolic health.


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