Association of PAF and its metabolic enzymes with GGT and the Fatty Liver Index in healthy volunteers

2021 ◽  
Vol 19 ◽  
Author(s):  
Paraskevi Detopoulou ◽  
Tzortzis Nomikos ◽  
Elizabeth Fragopoulou ◽  
Smaragdi Antonopoulou

Background: Platelet-activating factor (PAF) is a lipid inflammatory mediator implicated in liver disease. Its main biosynthetic enzymes are cytidine diphosphate (CDP)-choline:1-alkyl-2-acetyl-sn-glycerol-cholinephosphotransferase (PAF-CPT) and acetyl-coenzyme A: lyso-PAF-acetyltransferases (Lyso-PAF-AT), while PAF acetylhydrolase (PAF-AH) and lipoprotein-associated phospholipase A2 (Lp-PLA2) degrade PAF. Objective: To explore the relation of PAF metabolism with liver diseases and non-alcoholic fatty liver disease, as reflected by the fatty liver index (FLI). Methods: In 106 healthy volunteers, PAF concentration, the activity of its metabolic enzymes, and gamma-glutamyl transferase (GGT) were measured in whole blood, leukocytes, and serum, respectively, and the FLI was calculated. Partial correlations and linear regression models were used. Results: In males, serum GGT activity was positively correlated with abdominal fat (as assessed by analysis of a manually defined region of interest in dual-energy X-ray absorptiometry), triacylglycerols, bound-PAF, and Lp-PLA2, while the FLI was positively correlated with Lp-PLA2 activity. In females, serum GGT activity was negatively associated with high-density lipoprotein cholesterol (HDL-C) (age-adjusted correlations, all p<0.05). Lp-PLA2 was a significant determinant of serum GGT activity in males after controlling for age, low-density lipoprotein cholesterol (LDL-C), and abdominal fat. The addition of bound-PAF in the model significantly increased the explained variance of serum GGT activity (total variance explanation 30%). Conclusions : Bound-PAF and Lp-PLA2 activity predicted serum GGT activity, while Lp-PLA2 was also related to FLI. Our findings shed light on the metabolic pathways linking Lp-PLA2 to other atherosclerosis and/or oxidative markers, such as HDL-C, LDL-C, GGT, and FLI, and underline the important role of PAF.

Author(s):  
Jelena Janac ◽  
Aleksandra Zeljkovic ◽  
Zorana Jelic-Ivanovic ◽  
Vesna Dimitrijevic-Sreckovic ◽  
Milica Miljkovic ◽  
...  

Background Non-alcoholic fatty liver disease is a frequent ailment with known complications, including those within the cardiovascular system. Associations between several indicators of high-density lipoprotein metabolism and function with clinical and laboratory parameters for the assessment of fatty liver index, a surrogate marker of non-alcoholic fatty liver disease, were evaluated. Methods The study comprised 130 patients classified according to fatty liver index values: fatty liver index < 30, fatty liver index 30–59 (the intermediate group) and fatty liver index ⩾ 60. Lecithin–cholesterol acyltransferase and cholesteryl ester transfer protein activities were determined. Paraoxonase 1 concentration and its activity, paraoxonase 3 concentration and high-density lipoprotein subclass distribution were assessed. Results Increased lecithin–cholesterol acyltransferase activity correlated with increased fatty liver index ( P < 0.001). Paraoxonase 3 concentration was lower in the fatty liver index ⩾ 60 group compared with the fatty liver index < 30 group ( P < 0.05). Cholesteryl ester transfer protein activity, paraoxonase 1 concentration and its activity did not significantly differ across the fatty liver index groups. The relative proportion of small-sized high-density lipoprotein 3 subclass was higher in the fatty liver index ⩾ 60 group compared with the other two fatty liver index groups ( P < 0.01). Lecithin–cholesterol acyltransferase activity positively associated with the fatty liver index ⩾ 60 group and remained significant after adjustment for other potential confounders. Only the triglyceride concentration remained significantly associated with lecithin–cholesterol acyltransferase activity when the parameters that constitute the fatty liver index equation were examined. Conclusions Higher lecithin–cholesterol acyltransferase activity is associated with elevated fatty liver index values. Significant independent association between triglycerides and lecithin–cholesterol acyltransferase activity might indicate a role of hypertriglyceridaemia in alterations of lecithin–cholesterol acyltransferase activity in individuals with elevated fatty liver index.


Biomolecules ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. 435 ◽  
Author(s):  
Bihui Liu ◽  
Jing Zhang ◽  
Peng Sun ◽  
Ruokun Yi ◽  
Xiaoyan Han ◽  
...  

A high-fat diet-induced C57BL/6N mouse model of non-alcoholic fatty liver disease (NAFLD) was established. The effect and mechanism of Raw Bowl Tea polyphenols (RBTP) on preventing NAFLD via regulating intestinal function were observed. The serum, liver, epididymis, small intestine tissues, and feces of mice were examined by biochemical and molecular biological methods, and the composition of RBTP was analyzed by HPLC assay. The results showed that RBTP could effectively reduce the body weight, liver weight, and liver index of NAFLD mice. The serum effects of RBTP were: (1) decreases in alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AKP), total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), D-lactate (D-LA), diamine oxidase (DAO), lipopolysaccharide (LPS), and an increase of high density lipoprotein cholesterol (HDL-C) levels; (2) a decrease of inflammatory cytokines such as interleukin 1 beta (IL-1β), interleukin 4 (IL-4), interleukin 6 (IL-6), interleukin 10 (IL-10), tumor necrosis factor alpha (TNF-α), and interferon gamma (INF-γ); (3) a decrease the reactive oxygen species (ROS) level in liver tissue; and (4) alleviation of pathological injuries of liver, epididymis, and small intestinal tissues caused by NAFLD and protection of body tissues. qPCR and Western blot results showed that RBTP could up-regulate the mRNA and protein expressions of LPL, PPAR-α, CYP7A1, and CPT1, and down-regulate PPAR-γ and C/EBP-α in the liver of NAFLD mice. In addition, RBTP up-regulated the expression of occludin and ZO-1, and down-regulated the expression of CD36 and TNF-α in the small intestines of NAFLD mice. Studies on mice feces showed that RBTP reduced the level of Firmicutes and increased the minimum levels of Bacteroides and Akkermansia, as well as reduced the proportion of Firmicutes/Bacteroides in the feces of NAFLD mice, which play a role in regulating intestinal microecology. Component analysis showed that RBTP contained seven polyphenolic compounds: Gallic acid, (-)-epigallocatechin, catechin, L-epicatechin, (-)-epigallocatechin gallate, (-)-gallocatechin gallate, and (-)-epicatechin gallate (ECG), and high levels of caffeine, (-)-epigallocatechin (EGC), and ECG. RBTP improved the intestinal environment of NAFLD mice with the contained active ingredients, thus playing a role in preventing NAFLD. The effect was positively correlated with the dose of 100 mg/kg, which was even better than that of the clinical drug bezafibrate.


2020 ◽  
Author(s):  
Jae-Hyung Roh ◽  
Jae-Hyeong Park ◽  
Hanbyul Lee ◽  
Yong-Hoon Yoon ◽  
Minsu Kim ◽  
...  

Abstract Background Heart failure (HF) is relatively common cardiovascular disease with high mortality and morbidity. Although it is associated with many cardiovascular risk factors, the association between nonalcoholic fatty liver disease (NAFLD), the most common chronic liver disease, and HF has not been evaluated in a large-scale cohort study. Thus, we evaluated the ability of the fatty liver Index (FLI), a surrogate marker of NAFLD, to predict the development of HF in healthy individuals. Methods We analyzed the association between the FLI and new-onset HF with multivariate Cox proportional-hazards models in 308,578 healthy persons without comorbidities who underwent the National Health check-ups in the republic of Korea from 2009 to 2014. Results A total of 2,532 subjects (0.8%) were newly diagnosed with HF during the study period (a median of 5.4 years). We categorized our subjects into quartile groups according to FLI (Q1, 0-4.9; Q2, 5.0-12.5; Q3, 12.6-31.0; and Q4, >31.0). The cumulative incidence of HF was significantly higher in the highest FLI group than in the lowest FLI group (Q1, 307 [0.4%] and Q4, 890 [1.2%]; P<0.001). Adjusted hazard ratio (HRs) indicated that the highest FLI group was independently associated with an increased risk for HF (HR between Q4 and Q1, 2.709; 95% confidence interval=2.380-3.085; P<0.001). FLI was significantly associated with an increased risk of new-onset HF regardless of their baseline characteristics.Conclusions Higher FLI was independently associated with increased risk of HF in a healthy Korean population.


2022 ◽  
Vol 8 ◽  
Author(s):  
Luciana Marc ◽  
Adelina Mihaescu ◽  
Raluca Lupusoru ◽  
Iulia Grosu ◽  
Florica Gadalean ◽  
...  

Background: Changing the term/concept of the non-alcoholic fatty liver disease (NAFLD) to metabolic dysfunction associated fatty liver disease (MAFLD) may broaden the pathological definition that can include chronic renal involvement, and, possibly, changes chronic kidney disease's (CKD's) epidemiological association with liver disease, because CKD is associated with metabolic disorders and almost all patients with CKD present some form of an atherogenic dyslipidemia. Our study explores the relationship between MAFLD and CKD using Transient Elastography (TE) with a Controlled Attenuated Parameter (CAP).Methods: We evaluated 335 patients with diabetes with MAFLD and with high CKD risk using TE with CAP (FibroScan®). The CKD was defined according to Kidney Disease Improving Global Outcomes (KDIGO) 2012 guidelines. Logistic regression and stepwise multiple logistic regression were used to evaluate the factors associated with CKD. In addition, a receiver operating characteristic curve (ROC) analysis was used to assess the performance of CAP and TE in predicting CKD and its optimal threshold.Results: The prevalence of CKD in our group was 60.8%. Patients with CKD had higher mean liver stiffness measurements (LSM) and CAP values than those without CKD. We found that hepatic steatosis was a better predictor of CKD than fibrosis. Univariate regression showed that CAP values &gt;353 dB/m were predictive of CKD; while the multivariate regression analysis (after adjustment according to sex, body mass index (BMI), low-density lipoprotein cholesterol (LDLc), and high-density lipoprotein cholesterol (HDLc), and fasting glucose) showed that CAP values &gt;353 dB/m were more strongly associated with the presence of CKD compared to the LSM (fibrosis) values.Conclusion: In patients with MAFLD, CAP-assessed steatosis appears to be a better predictor of CKD compared to LSM-assessed hepatic fibrosis.


2021 ◽  
Vol 000 (000) ◽  
pp. 000-000
Author(s):  
Anne-Marieke van Dijk ◽  
Sjoerd Dingerink ◽  
Felix Patience Chilunga ◽  
Karlijn Anna Catharina Meeks ◽  
Silver Bahendeka ◽  
...  

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