Evaluation of the severity of nonalcoholic fatty liver disease by the analysis of serum exosomal miRNA expression

2021 ◽  
Author(s):  
Jeong-An Gim ◽  
Soo Min Bang ◽  
Young-Sun Lee ◽  
Yoonseok Lee ◽  
Sun Young Yim ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Mrna Expression ◽  
Nonalcoholic Fatty Liver Disease ◽  
Mirna Expression ◽  
Fatty Liver Disease ◽  
Expression Data ◽  
Nonalcoholic Fatty Liver ◽  
Exosomal Mirnas ◽  
Mirna Expression Data

Abstract Noninvasive modalities exhibit limited diagnostic performance for evaluating the severity of nonalcoholic fatty liver disease (NAFLD). MicroRNAs (miRNAs) serve as useful biomarkers for diagnosing and monitoring disease progression and treatment response. Here, we evaluated whether serum exosomal miRNAs can be used to clinically predict the severity of NAFLD. Exosomal miRNAs were isolated from the sera of 41 NAFLD patients (diagnosed using biopsy) for array profiling. To compare differentially expressed miRNAs, the degree of severity was determined using inflammation, steatosis, ballooning, and NAFLD activity score (NAS). The correlation of miRNAs with clinical and biochemical parameters was analyzed. The correlation between miRNA and mRNA expression was analyzed by comparing our miRNA expression data with publicly available mRNA expression data. Twenty-five, eleven, thirteen, and fourteen miRNAs correlated with inflammation score, steatosis score, ballooning score, and NAS, respectively. Thirty-three significant correlations were observed between twenty-seven miRNAs and six clinical variables (age, ALP, AST, ALT, GGT, and NAS). In fibrosis, 52 and 30 interactions corresponding to high miRNA-low mRNA and low miRNA-high mRNA expression, respectively, were observed. We demonstrated that serum exosomal miRNAs can be used to evaluate NAFLD severity and also delineate potential targets for NAFLD treatment.

scholarly journals Evaluation of the severity of nonalcoholic fatty liver disease through analysis of serum exosomal miRNA expression

PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0255822
Author(s):  
Jeong-An Gim ◽  
Soo Min Bang ◽  
Young-Sun Lee ◽  
Yoonseok Lee ◽  
Sun Young Yim ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Mrna Expression ◽  
Nonalcoholic Fatty Liver Disease ◽  
Mirna Expression ◽  
Fatty Liver Disease ◽  
Nonalcoholic Fatty Liver ◽  
Diagnosis And Prognosis ◽  
Exosomal Mirnas ◽  
Exosomal Mirna

Noninvasive techniques for evaluating the severity of nonalcoholic fatty liver disease (NAFLD) have shown limited diagnostic performance. MicroRNAs (miRNAs) are useful biomarkers for diagnosing and monitoring the progression and treatment response to several diseases. Here, we evaluated whether serum exosomal miRNAs could be used for the diagnosis and prognosis of NAFLD severity. Exosomal miRNAs were isolated from the sera of 41 patients with NAFLD (diagnosed using liver biopsy) for microarray profiling. The degree of NAFLD severity was determined using inflammation, steatosis, and ballooning scores and the NAFLD activity score (NAS). Correlations between miRNA expression, clinical and biochemical parameters, and mRNA expression were analyzed. Overall, 25, 11, 13, and 14 miRNAs correlated with the inflammation score, steatosis score, ballooning score, and NAS, respectively, with 33 significant correlations observed between 27 miRNAs and six clinical variables. Eight miRNAs (let-7b-5p, miR-378h, -1184, -3613-3p, -877-5p, -602, -133b, and 509-3p) showed anticorrelated patterns with the corresponding mRNA expression. In fibrosis, 52 and 30 interactions corresponding to high miRNA-low mRNA and low miRNA-high mRNA expression, respectively, were observed. The present results therefore suggest that serum exosomal miRNAs can be used to evaluate NAFLD severity and identify potential targets for NAFLD treatment.

scholarly journals Endocannabinoid Receptors Gene Expression in Morbidly Obese Women with Nonalcoholic Fatty Liver Disease

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Teresa Auguet ◽  
Alba Berlanga ◽  
Esther Guiu-Jurado ◽  
Ximena Terra ◽  
Salomé Martinez ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Mrna Expression ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Enzyme Linked Immunosorbent Assay ◽  
Morbidly Obese ◽  
Receptor Subtypes ◽  
Obese Women ◽  
Nonalcoholic Fatty Liver

Background. Recent reports suggest a role for the endocannabinoid system in the pathology of nonalcoholic fatty liver disease (NAFLD). The aim of this study was to investigate the relationship between liver expression of cannabinoid (CB) receptor subtypes, CB1 and CB2, in morbidly obese (MO) women with different histological stages of NAFLD.Methods. We analysed hepatic CB1 and CB2 mRNA expression, and the expression of genes involved in lipid metabolism in 72 MO women, subclassified by liver histology into MO with normal liver (NL,n=16), simple steatosis (SS,n=28), and nonalcoholic steatohepatitis (NASH,n=28) by enzyme-linked immunosorbent assay and RT-PCR.Results. We found that CB1 mRNA expression was significantly higher in NASH compared with SS and correlated negatively with PPARα. Regarding CB2, CB2 mRNA expression correlated positively with ACC1, PPARγ, IL6, TNFα, resistin, and adiponectin.Conclusions. The increased expression of CB1 in NASH and the negative correlation with PPARαsuggest a deleterious role of CB1 in NAFLD. Regarding CB2, its positive correlation with the anti-inflammatory molecule adiponectin and, paradoxically, with inflammatory genes suggests that this receptor has a dual role. Taken together, our results suggest that endocannabinoid receptors might be involved in the pathogenesis of NAFLD, a finding which justifies further study.

scholarly journals Predicting Nonalcoholic Fatty Liver Disease through a Panel of Plasma Biomarkers and MicroRNAs in Female West Virginia Population

2020 ◽  
Vol 21 (18) ◽  
pp. 6698
Author(s):  
Sneha S. Pillai ◽  
Hari Vishal Lakhani ◽  
Mishghan Zehra ◽  
Jiayan Wang ◽  
Anum Dilip ◽  
...  
Keyword(s):  
Liver Disease ◽  
Blood Glucose ◽  
West Virginia ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Mirna Expression ◽  
Fatty Liver Disease ◽  
Fasting Blood Glucose ◽  
The West ◽  
Nonalcoholic Fatty Liver

(1) Background: Nonalcoholic fatty liver disease (NAFLD) is primarily characterized by the presence of fatty liver, hepatic inflammation and fibrogenesis eventually leading to nonalcoholic steatohepatitis (NASH) or cirrhosis. Obesity and diabetes are common risk factors associated with the development and progression of NAFLD, with one of the highest prevalence of these diseased conditions in the West Virginia population. Currently, the diagnosis of NAFLD is limited to radiologic studies and biopsies, which are not cost-effective and highly invasive. Hence, this study aimed to develop a panel and assess the progressive levels of circulatory biomarkers and miRNA expression in patients at risk for progression to NASH to allow early intervention strategies. (2) Methods: In total, 62 female patients were enrolled and blood samples were collected after 8–10 h of fasting. Computed tomography was performed on abdomen/pelvis following IV contrast administration. The patients were divided into the following groups: Healthy subjects with normal BMI and normal fasting blood glucose (Control, n = 20), Obese with high BMI and normal fasting blood glucose (Obese, n = 20) and Obese with high fasting blood glucose (Obese + DM, n = 22). Based on findings from CT, another subset was created from Obese + DM group with patients who showed signs of fatty liver infiltration (Obese + DM(FI), n = 10). ELISA was performed for measurement of plasma biomarkers and RT-PCR was performed for circulating miRNA expression. (3) Results: Our results show significantly increased levels of plasma IL-6, Leptin and FABP-1, while significantly decreased level of adiponectin in Obese, Obese + DM and Obese + DM(FI) group, as compared to healthy controls. The level of CK-18 was significantly increased in Obese + DM(FI) group as compared to control. Subsequently, the expression of miR-122, miR-34a, miR-375, miR-16 and miR-21 was significantly increased in Obese + DM and Obese + DM(FI) group as compared to healthy control. Our results also show distinct correlation of IL-6, FABP-1 and adiponectin levels with the expression of miRNAs in relation to the extent of NAFLD progression. (4) Conclusion: Our results support the clinical application of these biomarkers and miRNAs in monitoring the progression of NAFLD, suggesting a more advanced diagnostic potential of this panel than conventional methods. This panel may provide an appropriate method for early prognosis and management of NAFLD and subsequent adverse hepatic pathophysiology, potentially reducing the disease burden on the West Virginia population.

scholarly journals Paraoxonase Activity and Expression Is Modulated by Therapeutics in Experimental Rat Nonalcoholic Fatty Liver Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
O. Hussein ◽  
J. Zidan ◽  
K. Abu Jabal ◽  
I. Shams ◽  
S. Szvalb ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Mrna Expression ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Chow Diet ◽  
Deficient Diet ◽  
Total Period ◽  
Nonalcoholic Fatty Liver ◽  
Group 15

Objective. The objective of the present study is to investigate the effect of rosiglitazone, metformin, ezetimibe, and valsartan (alone or in combinations) on paraoxonase (PON) activity and PON-mRNA expression in nonalcoholic fatty liver disease (NAFLD).Methods. 54 Male Sprague–Dawley rats were divided to 9 groups: chow diet group (15 weeks); methionine-choline-deficient diet (MCDD) group (15 weeks); MCDD-treated groups for the last 6 weeks with either metformin (M), rosiglitazone (R), metformin plus rosiglitazone (M+R), ezetimibe (E), valsartan (V), or a combination of R+M+V or of R+M+V+E for a total period of 15 weeks.Results. PON activities in serum and liver were decreased in MCDD rats. PON activity in serum increased significantly in all treatment groups. PON activity in liver was also increased significantly, except only in groups R, E, V, R+M+V, and R+M+V+E. Liver PON3 mRNA expression increased significantly in groups R+M, E, V, R+M+V, and R+M+V+E whereas liver PON2 mRNA expression increased significantly in MCDD, R+M, E, V, R+M+V, and R+M+V+E.Conclusions. PON activities in serum and liver were decreased in NAFLD. Treatment with insulin sensitizers, ezetimibe, and valsartan increased PON activity and reduced oxidative stress both in serum and liver.

scholarly journals Deregulation of Secreted Frizzled-Related Protein 5 in Nonalcoholic Fatty Liver Disease Associated with Obesity

2021 ◽  
Vol 22 (13) ◽  
pp. 6895
Author(s):  
Laia Bertran ◽  
Marta Portillo-Carrasquer ◽  
Carmen Aguilar ◽  
José Antonio Porras ◽  
David Riesco ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Mrna Expression ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Wnt Pathway ◽  
Normal Weight ◽  
Related Protein ◽  
Very Low Calorie Diet ◽  
Nonalcoholic Fatty Liver

Secreted frizzled-related protein 5 (SFRP5), an antagonist of the noncanonical WNT pathway, has a controversial role in liver disease. The aim of this study was to analyze the role of SFRP5 and the noncanonical WNT pathway in nonalcoholic fatty liver disease (NAFLD). Plasma SFRP5 levels were determined by ELISA in women with normal weight (NW; n = 20) and morbid obesity (MO; n = 69). Women with MO were subclassified according to hepatic histology into normal liver (NL; n = 28), NAFLD (n = 41) (simple steatosis (SS; n = 24), and nonalcoholic steatohepatitis (NASH; n = 17)). We used RT-qPCR to evaluate the hepatic mRNA expression of SFRP5, WNT5A, and JNK in women with MO. SFRP5 levels were lower in NW than in MO patients who underwent a very low-calorie diet before surgery. Hepatic SFRP5 mRNA expression was higher in SS than in NL or NASH; additionally, patients with hepatic inflammation or ballooning presented lower SFRP5 abundance. WNT5A and JNK expression was enhanced in NAFLD compared with NL. In conclusion, circulating SFRP5 levels depend on the diet, and hepatic SFRP5 seems to have a protective role in the first steps of NAFLD; however, SFRP5 could be deregulated in an advanced stage while WNT5A and JNK are activated, promoting liver damage.

scholarly journals Protective Effect of Cudrania tricuspidata Extract against High-Fat Diet Induced Nonalcoholic Fatty Liver Disease through Nrf-2/HO-1 Pathway

Molecules ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 2434
Author(s):  
Jitendra Shrestha ◽  
Dong-Jae Baek ◽  
Yoon-Sin Oh ◽  
Sam-Seok Cho ◽  
Sung-Hwan Ki ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Mrna Expression ◽  
Nonalcoholic Fatty Liver Disease ◽  
High Fat Diet ◽  
Fatty Liver Disease ◽  
Expression Level ◽  
High Fat ◽  
Cudrania Tricuspidata ◽  
Nonalcoholic Fatty Liver

Nonalcoholic fatty liver disease is the most common chronic disease affecting a wide range of the world’s population and associated with obesity-induced metabolic syndrome. It is possibly emerging as a leading cause of life-threatening liver diseases for which a drug with a specific therapeutic target has not been developed yet. Previously, there have been reports on the benefits of Cudrania tricuspidata (CT) for treating obesity and diabetes via regulation of metabolic processes, such as lipogenesis, lipolysis, and inflammation. In this study, we investigated the ameliorative effect of orally administered 0.25% and 0.5% (w/w) CT mixed with high-fat diet (HFD) to C57BL/6J mice for 7 weeks. It was found that body weight, fat mass, hepatic mass, serum glucose level, and liver cholesterol levels were significantly reduced after CT treatment. In CT-treated HFD-fed mice, the mRNA expression levels of hepatic lipogenic and inflammatory cytokine-related genes were markedly reduced, whereas the expression level of epididymal lipogenic genes was increased. The mRNA expression level of beta-oxidation and Nrf-2/HO-1 genes significantly increased in CT-treated obese mice livers. We propose that CT alleviates hepatic steatosis by reducing oxidative stress and inflammation.

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