scholarly journals CCL25 mediates inflammatory crosstalk between adipose and liver in non-alcoholic fatty liver disease

2021 ◽  
Author(s):  
Richard Parker ◽  
John Drake ◽  
Chris Weston ◽  
David H Adams
Keyword(s):  
Gene Expression ◽  
Liver Disease ◽  
Fatty Liver ◽  
Liver Tissue ◽  
Fatty Liver Disease ◽  
Enzyme Linked Immunosorbent Assay ◽  
Leukocyte Trafficking ◽  
Alcoholic Fatty Liver ◽  
Hepatic Sinusoid ◽  
Alcoholic Fatty Liver Disease

Background and Aims: Obesity is closely associated with non-alcoholic fatty liver disease (NAFLD). We investigated expression of the CC-chemokine CCL25 in adipose tissue (AT) and its relation to hepatic inflammation. Methods: Primary human tissue was used for all experiments. CCL25 concentration in serum was measured with enzyme-linked immunosorbent assay (ELISA). Gene expression of CCL25 was measured with polymerase chain reaction. Protein expression was assessed with ELISA and immunohistochemistry. Leukocyte trafficking was investigated in a dynamic assay to model the hepatic sinusoid. Expression of CCR9 on liver-infiltrating leukocytes analysed with flow cytometry. Results: Circulating CCL25 was increased in obesity. Gene expression of CCL25 in AT was several-fold higher than in liver, although protein levels of CCL25 were comparable. Soluble CCL25 in flow media increased leukocyte trafficking across hepatic endothelium. Greater numbers of CCR9+ cells were seen in liver tissue from patients with NAFLD, where the greatest difference was in the number of CD14+CD16+ monocytes. Conclusions: CCL25 and its cognate receptor CCR9 mediate a novel pathway of inflammatory crosstalk between adipose and liver tissue in NAFLD.

scholarly journals Evaluation of potential gene expression as early markers of insulin resistance and non-alcoholic fatty liver disease in the Indonesian population

2018 ◽  
Vol 23 (2) ◽  
pp. 84
Author(s):  
Eunice Limantara ◽  
Felicia Kartawidjajaputra ◽  
Antonius Suwanto
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Model Assessment ◽  
Gene Expressions ◽  
Alcoholic Fatty Liver ◽  
Early Markers ◽  
Alcoholic Fatty Liver Disease

Early detection of insulin resistance (IR) or non-alcoholic fatty liver disease (NAFLD) is crucial to preventing future risks of developing chronic diseases. The Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), Liver Fat Score (LFS), and Fatty Liver Index (FLI) are generally employed to measure severity stages of IR and NAFLD. The study of gene expressions could explain the molecular mechanisms that occur early on in IR and NAFLD; thus providing potential early markers for both diseases. This study was conducted to evaluate the gene expressions that could potentially be early markers of IR and NAFLD. All participants (n = 21) had normal blood glucose and were categorized as without hepatosteatosis (n = 10), at higher risk of hepatosteatosis (n = 6), and hepatosteatosis (n = 5). Gene expression analysis was performed using the 2-∆∆CT relative quantification method. There were significant differences in galnt2 (p < 0.002) and sirt1 (p < 0.010) expression between the first and the third tertiles of HOMA-IR; and in ptpn1 (p < 0.012) expression between the first and the second tertiles of LFS. In conclusion, the expressions of galnt2 and sirt1 could be used as early markers of IR, while the expression of ptpn1 could be employed as an early marker of NAFLD.

scholarly journals Rosiglitazone and bezafibrate modulate gene expression in a rat model of non-alcoholic fatty liver disease - A historical prospective

2013 ◽  
Vol 12 (1) ◽  
Author(s):  
Hemda Schmilovitz-Weiss ◽  
Edith Hochhauser ◽  
Michal Cohen ◽  
Yelena Chepurko ◽  
Smadar Yitzhaki ◽  
...  
Keyword(s):  
Gene Expression ◽  
Liver Disease ◽  
Fatty Liver ◽  
Rat Model ◽  
Fatty Liver Disease ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

scholarly journals Assessment of non-alcoholic fatty liver disease (NAFLD) severity with novel serum-based markers: A pilot study

PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0260313
Author(s):  
Atul Goyale ◽  
Anjly Jain ◽  
Colette Smith ◽  
Margarita Papatheodoridi ◽  
Marta Guerrero Misas ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Positive Likelihood Ratio ◽  
Public Health Issue ◽  
Enzyme Linked Immunosorbent Assay ◽  
Roc Curve Analysis ◽  
Cross Sectional ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Background/Aims Non-alcoholic fatty liver disease (NAFLD) represents a significant public health issue. Identifying patients with simple steatosis from those with non-alcoholic steatohepatitis (NASH) is crucial since NASH is correlated with increased morbidity and mortality. Serum-based markers, including adipokines and cytokines, are important in the pathogenesis and progression of NAFLD. Here we assessed the usefulness of such markers in patients with NAFLD. Methods This prospective, cross-sectional study included 105 adult patients with varying severity of NAFLD. Twelve serum-based markers were measured by 3 biochip platforms and 2 enzyme-linked immunosorbent assay (ELISA) methods. We also developed a NAFLD individual fibrosis index (NIFI) using the serum-based markers mostly correlated with fibrosis severity. Results Sixty-one out of 105 patients were male (58.1%) with mean age was 53.5 years. Higher Interleukin-6 (IL-6) increased (p = 0.0321) and lower Matrix Metalloproteinase-9 (MMP-9) serum levels (p = 0.0031) were associated with higher fibrosis as measured by Fibroscan® in multivariable regression analysis. Using receiver-operating characteristic (ROC) curve analysis for the NIFI, area under the curve for predicting Fibroscan values ≥ 7.2 kPa was 0.77 (95%CI: 0.67, 0.88, p<0.001), with sensitivity of 89.3%, specificity of 57.9% and a positive likelihood ratio of 2.8. Conclusions Increasing fibrosis severity in NAFLD is associated with differential expression of IL-6 and MMP-9. NIFI could be valuable for the prediction of advanced NAFLD fibrosis and potentially help avoid unnecessary interventions such as liver biopsy in low-risk patients.

scholarly journals A Diet-Induced Pediatric Model of Non Alcoholic Fatty Liver Disease Using Neonatal Iberian Pigs (OR26-02-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Gabriella Hernandez ◽  
Victoria Smith ◽  
Mieko Temple ◽  
Darin Bennet ◽  
Daniel Columbus ◽  
...  
Keyword(s):  
Gene Expression ◽  
Body Weight ◽  
Liver Disease ◽  
Liver Injury ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Binding Protein ◽  
Alcoholic Fatty Liver ◽  
Element Binding Protein ◽  
Alcoholic Fatty Liver Disease

Abstract Objectives The prevalence of non-alcoholic fatty liver disease (NAFLD) in children has increased over the past decades, creating a need for animal models that recapitulate the features of the pediatric disease. Iberian pigs have a leptin-resistant phenotype characterized by hyperleptinemia, hyperphagia, and extreme adipogenesis. We hypothesized that neonatal Iberian pigs fed a high-fat high-fructose (HFF) diet will develop a pattern of liver injury resembling pediatric NAFLD. In addition, we sought to determine if a mixture of probiotics would prevent the disease. Methods Animals were fed 1 of 4 diets containing (g/kg body weight × d) 0 g fructose, 11 g fat and 199 kcal (CON-N; n = 8), 22 g fructose, 16 g fat and 300 kcal (HFF-N; n = 6), CON + probiotic (CON-P; n = 6), or HFF + probiotic (HFF-P; n = 6) every 6 h for 70 d. The probiotic mixture (6.2 × 104cfu/mL) contained Pediococcus, Lactobacillus and Bacillus. Body weight was recorded every 3 d. Serum markers of liver injury and dyslipidemia were measured on d 65 at 2 h post feeding. Fasting leptin, insulin, glucose and homeostatic model assessment (HOMA) values were assessed on d 70. Liver tissue was collected on d 70 for histology, triacylglyceride (TG) quantification, and gene expression of tumor necrosis factor (TNF) α, tumor growth factor (TGF) β, interleukin (IL) 1α, peroxisome proliferator-activated receptor (PPAR) γ, carbohydrate-responsive element-binding protein (ChREBP) and sterol regulatory element-binding protein (SREBP) 1c. Results Body weight was higher in CON-P, and insulin and HOMA values in HFF-P and CON-P (P ≤ 0.05). Leptin, alanine and aspartate aminotransferases, alkaline phosphatase, lactate dehydrogenase and total bilirubin were increased (P ≤ 0.001), and high and low density lipoproteins decreased (P ≤ 0.05) in HFF-N and HFF-P. Livers in HFF-P and HFF-N had higher relative weight and TG (P ≤ 0.001), micro and macrovesicular steatosis, ballooning degeneration, Mallory-denk bodies, inflammation and necrosis, increased gene expression of TNFα, TGFβ, IL1α and PPARγ (P ≤ 0.001), and decreased ChREBP (P ≤ 0.001). Conclusions Iberian pigs fed a HFF diet recapitulate many pediatric NAFLD-associated features, in the absence of obesity and independently of probiotic supplementation, suggesting a potentially suitable model for pediatric NAFLD research. Funding Sources ARI, AcornSeekers.

Su1036 Hepatic Apolipoprotein A-IV Gene Expression Is Increased in Non-Alcoholic Fatty Liver Disease and Is Modulated by Gender and Inflammation

2015 ◽  
Vol 148 (4) ◽  
pp. S-1045
Author(s):  
Nathan J. Shores ◽  
Melissa A. Verhague ◽  
Janet K. Sawyer ◽  
Adolfo Z. Fernandez ◽  
Lawrence L. Rudel ◽  
...  
Keyword(s):  
Gene Expression ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Alcoholic Fatty Liver ◽  
Apolipoprotein A ◽  
Hepatic Apolipoprotein ◽  
Alcoholic Fatty Liver Disease
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