scholarly journals HDL-Mediated Cholesterol Efflux and Plasma Loading Capacities Are Altered in Subjects with Metabolically- but Not Genetically Driven Non-Alcoholic Fatty Liver Disease (NAFLD)

Biomedicines ◽  
2020 ◽  
Vol 8 (12) ◽  
pp. 625
Author(s):  
Alessia Di Costanzo ◽  
Annalisa Ronca ◽  
Laura D’Erasmo ◽  
Matteo Manfredini ◽  
Francesco Baratta ◽  
...  

Background. Non-alcoholic fatty liver disease (NAFLD) increases the risk of atherosclerosis but this risk may differ between metabolically- vs. genetically-driven NAFLD. High-density lipoprotein (HDL)-mediated cholesterol efflux (CEC) and plasma loading capacity (CLC) are key factors in atherogenesis. Aims. To test whether CEC and CLC differ between metabolically- vs. genetically-determined NAFLD. Methods: CEC and CLC were measured in 19 patients with metabolic NAFLD and wild-type PNPLA3 genotype (Group M), 10 patients with genetic NAFLD carrying M148M PNPLA3 genotype (Group G), and 10 controls PNPLA3 wild-types and without NAFLD. CEC and CLC were measured ex vivo by isotopic and fluorimetric techniques using cellular models. Results: Compared with Group G, Group M showed reduced total CEC (−18.6%; p < 0.001) as well as that mediated by cholesterol transporters (−25.3% ABCA1; −16.3% ABCG1; −14.8% aqueous diffusion; all p < 0.04). No difference in CEC was found between Group G and controls. The presence of metabolic syndrome further impaired ABCG1-mediated CEC in Group M. Group M had higher plasma-induced CLC than Group G and controls (p < 0.001). Conclusions: Metabolically-, but not genetically-, driven NAFLD associates with dysfunctional HDL-meditated CEC and abnormal CLC. These data suggest that the mechanisms of anti-atherogenic protection in metabolic NAFLD are impaired.

2017 ◽  
Vol 26 (1) ◽  
pp. 59-67 ◽  
Author(s):  
Ahmed Elgebaly ◽  
Ibrahim A. I. Radwan ◽  
Mohamed M. AboElnas ◽  
Hamza H. Ibrahim ◽  
Moutaz F. M. Eltoomy ◽  
...  

Background: Resveratrol is a potential treatment option for management of non-alcoholic fatty liver disease (NAFLD) due to its anti-inflammatory, antioxidant properties, and calorie restriction-like effects. We aimed to synthesise evidence from published randomized clinical trials (RCTs) about the efficacy of resveratrol in the management of NAFLD.Methods: A computer literature search of PubMed, Scopus, Web of Science, and Cochrane Central was conducted using relevant keywords. Records were screened for eligible studies and data were extracted and synthesized using Review Manager Version 5.3 for windows. Subgroup analysis and sensitivity analysis were conducted.Results: Four RCTs (n=158 patients) were included in the final analysis. The overall effect estimates did not favor resveratrol group in terms of: serum ALT (MD -2.89, 95%CI [-15.66, 9.88], p=0.66), serum AST (MD -3.59, 95%CI [-13.82, 6.63], p=0.49), weight (MD -0.18, 95%CI [-0.92, 0.55], p=0.63), BMI (MD -0.10, 95 %CI [-0.43, 0.24], p=0.57), blood glucose level (MD -0.27, 95%CI [-0.55, 0.01], p=0.05), insulin level (MD -0.12, 95%CI [-0.69, 0.46], p=0.69), triglyceride level (MD 0.04, 95%CI [-0.45, 0.53], p=0.87), and LDL level (MD 0.21, 95%CI [-0.41, 0.83], p=0.51). Pooled studies were heterogeneous.Conclusion: Current evidence is insufficient to support the efficacy of resveratrol in the management of NAFLD. Resveratrol does not attenuate the degree of liver fibrosis or show a significant decrease in any of its parameters.Abbreviations: ALT: Alanine aminotransferase; AMPK: AMP-activated protein kinase; AST: Aspartate aminotransferase; BMI: Body mass index; CK-18: Cytokeratin-18; CRP: C-reactive protein; HC: Head circumference; HDL: High density lipoprotein; IL-6: Interleukin-6; LDL: Low density lipoprotein; MD: Mean difference; NAFLD: Non-alcoholic fatty liver disease; NASH: Non-alcoholic steatohepatitis; RCT: Randomized Controlled Trial; RR: Relative risk; SIRT1: Silent information regulation 2 homologue 1; TNF-α: Tumor necrosis factor α; WC: Waist circumference; WHR: Waist hip ratio.


2019 ◽  
Vol 56 (1) ◽  
pp. 28-33 ◽  
Author(s):  
Laura BOEMEKE ◽  
Fabiana Viegas RAIMUNDO ◽  
Márcia BOPP ◽  
Lara Rigon LEONHARDT ◽  
Sabrina Alves FERNANDES ◽  
...  

ABSTRACT BACKGROUND: Insulin resistance, especially that induced by obesity, plays a central role in the development of non-alcoholic fatty liver disease. Although the evaluation of overweight patients is important, the nutritional assessment tools used in clinical practice have limitations. Neck circumference (NC), from this, becomes a viable and low-cost alternative, which seems to be related to the accumulation of fat in the hepatic tissue. OBJECTIVE: To evaluate the association between NC and metabolic alterations in patients with non- alcoholic fatty liver disease. METHODS: A cross-sectional study performed in 82 patients, of whom 76 underwent liver biopsy. We performed weight, height, abdominal circumference and NC measures. Values of NC ≥42 cm and ≥36 cm were considered as altered for men and women, respectively. Laboratory tests and liver biopsy result were collected in the participants’ charts. We evaluated fasting blood glucose levels, insulin, glycosylated hemoglobin, triglycerides, total cholesterol, high density lipoprotein (HDL-C), low density lipoprotein (LDL-C), ferritin, alkaline phosphatase, gamma glutamyltransferase, albumin, total bilirubin, direct bilirubin, glutamic-oxalacetic transaminase, glutamic-pyruvic transaminase and the HOMA-IR index. RESULTS: We evaluated eighty-two patients. Patients with altered NC had increased body mass index (P=0.043), abdominal circumference (P=0.007), insulin (P=0.003) and HOMA-IR (P=0.029) when compared to those with adequate NC. NC was significantly correlated with reduced levels of high-density cholesterol (HDL-C) in men (r= -042, P<0.05), increased insulin levels in men and female (rs=0.47; P<0.05 and rs=0.51; P<0.01, respectively), as well as higher HOMA-IR index both males (rs=0.49; P<0.01) and female (rs=0.30; P<0.05). There was no significant association between NC and liver outcomes (r=0.145; P=0.36). CONCLUSION: NC is associated with the HOMA-IR index in patients with non-alcoholic fatty liver disease. NC can be used in the screening of insulin resistance in these patients, considering that insulin resistance plays a key role in the progression of the disease.


2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Emine Turkkan ◽  
Huseyin Dag ◽  
Okan Dikker ◽  
Nevin Cetin Dag ◽  
Alper Kacar ◽  
...  

Background: Omentin-1 is an adipocytokine secreted from visceral adipose tissue that is thought to increase insulin sensitivity. Non-alcoholic fatty liver disease (NAFLD) is a comparatively extensive problem in obese adolescents. Decreased omentin-1 levels have been reported in obese patients, but the relationship between NAFLD and omentin-1 is contradictory. Objectives: We aimed to evaluate the omentin-1 levels in the sera of obese adolescents with and without NAFLD and compare them with each other. Methods: In this study, a total of 88 adolescents (56 obese and 32 normal-weight) were enrolled. Abdominal ultrasonography (US) identified 28 obese adolescents with grade 2-3 hepatosteatosis constituting the NAFLD group and 28 without hepatosteatosis on US constituting the non-NAFLD group. The control group included 32 age- and gender-matched cases without hepatosteatosis and with normal percentile body mass index (BMI). Serum omentin-1 levels were evaluated and compared. Results: The mean age of the research group was 12.72 ± 1.91 years. Unsurprisingly, BMI, glycated hemoglobin (HbA1c), liver transaminases (AST, ALT), total cholesterol, triglyceride, low-density lipoprotein cholesterol (LDL), homeostatic model assessment for insulin resistance (HOMA-IR), and insulin rates were noticeably elevated in obese adolescents compared to controls (P < 0.05). However, omentin-1 and high-density lipoprotein cholesterol (HDL) levels were remarkably lower in the obese group (P < 0.05). No significant difference was found between the NAFLD and non-NAFLD groups regarding omentin-1, HbA1c, glucose, urea, creatinine, AST, C-reactive protein (CRP), total cholesterol, triglyceride, HDL, LDL, thyroid stimulating hormone, 25-hydroxyvitamin D3, HOMA-IR, and insulin. The BMI and ALT grades of the non-NAFLD group were notably lower than the NAFLD group (P < 0.05). While there was no significant difference between omentin-1 and other parameters in obese adolescents without NAFLD (P > 0.05), we found a significant difference between omentin-1 and BMI, AST, ALT, HOMA-IR, and insulin values in obese adolescents with NAFLD (P < 0.05). Conclusions: Omentin-1 levels were decreased in obese adolescents regardless of the presence of NAFLD. However, in obese patients with NAFLD, there was a significant difference between omentin-1 and several markers of obesity and insulin resistance.


2018 ◽  
Vol 96 (6) ◽  
pp. 537-543
Author(s):  
E. V. Sevostyanova ◽  
V. Ya. Polyakov ◽  
Yu. A. Nikolaev ◽  
I. M. Mitrofanov

Purpose of the study. To study frequency of occurrence and values ofparameters of the main risk factors for cardiovascular diseases in patients with hypertension in combination with non-alcoholic fatty liver disease. Material and methods. The analysis of 17,202 medical cards of patients (6,730 men, 10,472 women), which were examined and treated in the clinic of the Scientific Research Institute of Experimental and Clinical Medicine, Novosibirsk, was carried out. Of them - 3,087patients with arterial hypertension (AH), combined with non-alcoholic fatty liver disease (NAFLD) (main group); 13,384 patients with isolated arterial hypertension; 731 patients with NAFLD (comparison groups). According to the clinical and laboratory examination, the following risk factors were assessed: high blood pressure, obesity, elevated blood levels of total cholesterol, low-density lipoprotein cholesterol, triglycerides, glucose, uric acid, a low content of high-density lipoprotein cholesterol in the blood. Results. In patients with hypertension combined with NAFLD, in comparison with patients with isolated diseases, an increase in the values of the indices determining the main modifiable risk factors for cardiovascular diseases (hypertension, obesity, hyperglycemia, hypercholesterolemia, hyperuricemia) was revealed. Similar changes were detected in both men and women. Conclusion. An important role of risk factors for cardiovascular diseases, which together represent the clinical manifestations of the metabolic syndrome, has been identified in the development of comorbid pathology - AH and NAFLD. The data obtained indicate the need for differentiated, personified prevention and treatment of patients with this comorbid pathology with mandatory identification and correction of modifiable risk factors for cardiovascular diseases.


2020 ◽  
Author(s):  
Aakash Shahi ◽  
Narayan Gautam ◽  
Sanju Rawal ◽  
Uday Sharma ◽  
Archana Jayan

Abstract Background: Fatty liver disease is a common and major chronic liver disease. It has been implicated that patients have disorders of lipid metabolism and involved in the pathogenesis of fatty liver. Lipid profile plays a very important role in diagnosis of liver diseases hence it was designed to observe relationship between lipid profile and fatty liver disease (FLD) based on ultrasonography (USG).Method and methodology: This Cross-sectional and analytical study was undertaken in the Department of Internal Medicine with collaboration of Department of Radiology and Department of Biochemistry, Universal College of Medical Sciences-Teaching Hospital (UCMS-TH), Bhairahawa, Nepal from March 2019 to February 2020 in total 100 patients diagnosed with FLD by USG.Result: In 100 cases, the male to female ratio was 1.8:1. 56% of the total cases presented with alcoholic fatty liver disease (AFLD) while remaining 44% with non alcoholic fatty liver disease (NAFLD). The spectrum of lipid abnormality was observed with increased total cholesterol (TC), Low Density Lipoprotein (LDL), increased triglycerides (TG) and Very Low Density Lipoprotein (VLDL) in AFLD cases as compared to NAFLD cases. However, it has been observed that TG/HDL and Non-HDL/HDL were higher in NAFLD as compared to AFLD. There was statistical significant difference in HDL (p-value: 0.019) between alcoholic fatty liver disease grade 1 (AFLG1) and non-alcoholic fatty liver disease grade 1 (NAFLG1). Moreover, it was observed statistical significant difference in HDL between AFLG2 and NAFLG2 (p-value: 0.012).Conclusion:Elevated level of TG and decreased HDL has been implicated in the precipitation of the occlusive vascular disease. These parameters in conjunction with Non-HDL/HDL and TG/HDL can be useful in early screening and monitoring of dyslipidemia in the fatty liver patients to prevent cardiovascular diseases.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hee Kyung Shin ◽  
Jeong Hwan Park ◽  
Jung Hwan Yu ◽  
Young-Joo Jin ◽  
Young Ju Suh ◽  
...  

AbstractTelomere length has been linked to the prevalence and progression of metabolic disease. However, clinical implications of telomere length in biopsy-proven non-alcoholic fatty liver disease (NAFLD) patients remain unclear. Therefore, this study aimed to investigate the association of telomere length with the histological severity of NAFLD. The cross-sectional data derived from the prospectively enrolled Boramae NAFLD registry (n = 91) were analyzed. The liver tissues and clinical information were obtained from both NAFLD patients and non-NAFLD subjects. Binary logistic regression was performed to identify the independent association between telomere length and the histological severity of NAFLD. A total of 83 subjects with or without biopsy-proven NAFLD were included for analysis: non-NAFLD in 23 (27.7%), non-alcoholic fatty liver in 15 (18.1%), and non-alcoholic steatohepatitis (NASH) in 45 (54.2%). Telomere length measured from liver tissues showed a strong negative correlation (p < 0.001) with age, regardless of NAFLD status. Therefore, telomere length was corrected for age. Age-adjusted telomere length than decreased gradually with an increasing severity of fibrosis in patients with NAFLD (p < 0.028). In multivariate analysis, age-adjusted telomere length (odds ratio [OR] 0.59; 95% CI 0.37–0.92; p = 0.019) and high-density lipoprotein cholesterol (OR 0.94; 95% CI 0.80–0.99; p = 0.039) were independently associated with significant fibrosis. The age-adjusted telomere length tends to decrease along with the fibrosis stage of NAFLD. In particular, among the histological components of NAFLD, fibrosis severity seems to be related to telomere length in the liver.


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