scholarly journals DNA Hydroxymethylation at the Interface of the Environment and Nonalcoholic Fatty Liver Disease

2019 ◽  
Vol 16 (15) ◽  
pp. 2791 ◽  
Author(s):  
Stella Tommasi ◽  
Ahmad Besaratinia
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Current Knowledge ◽  
Hepatic Metabolism ◽  
Environmental Toxicants ◽  
Alcoholic Fatty Liver ◽  
Dna Hydroxymethylation ◽  
Nonalcoholic Fatty Liver ◽  
Underlying Mechanisms

Non-alcoholic fatty liver disease (NAFLD) is one of the most prevalent forms of chronic liver disorders among adults, children, and adolescents, and a growing epidemic, worldwide. Notwithstanding the known susceptibility factors for NAFLD, i.e., obesity and metabolic syndrome, the exact cause(s) of this disease and the underlying mechanisms of its initiation and progression are not fully elucidated. NAFLD is a multi-faceted disease with metabolic, genetic, epigenetic, and environmental determinants. Accumulating evidence shows that exposure to environmental toxicants contributes to the development of NAFLD by promoting mitochondrial dysfunction and generating reactive oxygen species in the liver. Imbalances in the redox state of the cells are known to cause alterations in the patterns of 5-hydroxymethylcytosine (5hmC), the oxidative product of 5-methylcytosine (5mC), thereby influencing gene regulation. The 5hmC-mediated deregulation of genes involved in hepatic metabolism is an emerging area of research in NAFLD. This review summarizes our current knowledge on the interactive role of xenobiotic exposure and DNA hydroxymethylation in the pathogenesis of fatty liver disease. Increasing the mechanistic knowledge of NAFLD initiation and progression is crucial for the development of new and effective strategies for prevention and treatment of this disease.

scholarly journals Recent Advances in Adipose Tissue Dysfunction and Its Role in the Pathogenesis of Non-Alcoholic Fatty Liver Disease

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3300
Author(s):  
Xiaoxiao Wang ◽  
Huiying Rao ◽  
Feng Liu ◽  
Lai Wei ◽  
Honggui Li ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Current Knowledge ◽  
Low Grade ◽  
Alcoholic Fatty Liver ◽  
Nonalcoholic Fatty Liver ◽  
Adipose Tissue Dysfunction ◽  
Adipose Dysfunction

Obesity is a serious ongoing health problem that significantly increases the incidence of nonalcoholic fatty liver disease (NAFLD). During obesity, adipose tissue dysfunction is obvious and characterized by increased fat deposition (adiposity) and chronic low-grade inflammation. The latter has been implicated to critically promote the development and progression of NAFLD, whose advanced form non-alcoholic steatohepatitis (NASH) is considered one of the most common causes of terminal liver diseases. This review summarizes the current knowledge on obesity-related adipose dysfunction and its roles in the pathogenesis of hepatic steatosis and inflammation, as well as liver fibrosis. A better understanding of the crosstalk between adipose tissue and liver under obesity is essential for the development of new and improved preventive and/or therapeutic approaches for managing NAFLD.

Increased hepcidin levels and non-alcoholic fatty liver disease in obese prepubertal children: a further piece to the complex puzzle of metabolic derangements

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Cosimo Giannini ◽  
Nella Polidori ◽  
Maria Alessandra Saltarelli ◽  
Francesco Chiarelli ◽  
Raffaella Basilico ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Iron Metabolism ◽  
Fatty Liver Disease ◽  
Positive Association ◽  
Obese Children ◽  
Alcoholic Fatty Liver ◽  
Prepubertal Children ◽  
Nonalcoholic Fatty Liver ◽  
Underlying Mechanisms

Abstract Introduction Several studies on obese youths and adults have reported increased hepcidin levels, which seems to be related to metabolic and iron metabolism alterations. The complete mechanisms involved in hepcidin increase remain to be elucidated, and particularly its role in the development of other known complications such as Nonalcoholic Fatty Liver Disease (NAFLD). NAFLD in prepubertal children might be of special interest in understanding the underlying mechanisms. Methods Anthropometric measurements, liver ultrasonography, lipid profile, liver function, oxidative stress, inflammatory state, and iron metabolism were studied in 42 obese prepubertal children and 33 healthy controls. We, therefore, evaluated the presence of possible correlations between Hepcidin and the other metabolic variables, and the possible association between NAFLD and iron metabolism. Results Hepcidin levels were significantly increased in the obese prepubertal children (p=0.001) with significant differences between obese children with and without NAFLD (p=0.01). Blood iron was lower in obese children (p=0.009). In the obese group, a negative correlation between hepcidin and both blood iron levels (p=0.01) and LagPHASE (p=0.02) was found. In addition, a positive association between hepcidin and NAFLD (p=0.03) was detected. Conclusions We suggest that an increase in hepcidin levels may represent an early step in iron metabolism derangements and metabolic alterations, including NAFLD, in prepubertal obese children.

New therapy for fatty liver

2018 ◽  
Vol 1 (2) ◽  
pp. 24-28
Author(s):  
Tanita Suttichaimongkol
Keyword(s):  
Oxidative Stress ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Lifestyle Modifications ◽  
Alcoholic Fatty Liver ◽  
Nonalcoholic Fatty Liver ◽  
Liver Insulin Resistance ◽  
Alcoholic Fatty Liver Disease ◽  
Related Mortality

Non-alcoholic fatty liver disease (NAFLD) is a leading cause of death from liver cirrhosis, endstage liver disease, and hepatocellular carcinoma. It is also associated with increased cardiovasculardisease and cancer related mortality. While lifestyle modifications are the mainstay of treatment,only a proportion of patients are able to make due to difficult to achieve and maintain, and so moretreatment options are required such as pharmacotherapy. This review presents the drugs used inmanaging NAFLD and their pharmacologic targets. Therapies are currently directed towards improvingthe metabolic status of the liver, insulin resistance, cell oxidative stress, apoptosis, inflammation orfibrosis. Several agents are now in large clinical trials and within the next few years, the availability oftherapeutic options for NAFLD will be approved.     Keywords: nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, fibrosis, cirrhosis  

Natural Aldose Reductase Inhibitor: A Potential Therapeutic Agent for Non-alcoholic Fatty Liver Disease

2020 ◽  
Vol 21 (6) ◽  
pp. 599-609 ◽  
Author(s):  
Longxin Qiu ◽  
Chang Guo
Keyword(s):  
Oxidative Stress ◽  
Liver Disease ◽  
Fatty Liver ◽  
Aldose Reductase ◽  
Fatty Liver Disease ◽  
Acid Oxidation ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Alcoholic Fatty Liver ◽  
Nonalcoholic Fatty Liver

Aldose reductase (AR) has been reported to be involved in the development of nonalcoholic fatty liver disease (NAFLD). Hepatic AR is induced under hyperglycemia condition and converts excess glucose to lipogenic fructose, which contributes in part to the accumulation of fat in the liver cells of diabetes rodents. In addition, the hyperglycemia-induced AR or nutrition-induced AR causes suppression of the transcriptional activity of peroxisome proliferator-activated receptor (PPAR) α and reduced lipolysis in the liver, which also contribute to the development of NAFLD. Moreover, AR induction in non-alcoholic steatohepatitis (NASH) may aggravate oxidative stress and the expression of inflammatory cytokines in the liver. Here, we summarize the knowledge on AR inhibitors of plant origin and review the effect of some plant-derived AR inhibitors on NAFLD/NASH in rodents. Natural AR inhibitors may improve NAFLD at least in part through attenuating oxidative stress and inflammatory cytokine expression. Some of the natural AR inhibitors have been reported to attenuate hepatic steatosis through the regulation of PPARα-mediated fatty acid oxidation. In this review, we propose that the natural AR inhibitors are potential therapeutic agents for NAFLD.

Cardiovascular Risk in Children with Nonalcoholic Fatty Liver Disease (NAFLD)

2020 ◽  
Vol 16 ◽  
Author(s):  
Anna Bobrus- Chociej ◽  
Natalia Wasilewska ◽  
Marta Flisiak- Jackiewicz ◽  
Dariusz Lebensztejn
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Current Knowledge ◽  
Scientific Evidence ◽  
Multisystem Disorder ◽  
Nonalcoholic Fatty Liver ◽  
Obesity Epidemic ◽  
The Metabolic Syndrome

: Nonalcoholic fatty liver disease (NAFLD) is a main cause of chronic liver disease in children. With the global obesity epidemic, the prevalence of NAFLD is increasing both in industrialized and developing countries. NAFLD is a multisystem disorder and a hepatic manifestation of the metabolic syndrome. Growing scientific evidence suggests that NAFLD is an independent risk factor for cardiovascular disease. This paper briefly describes the current knowledge concerning the association between NAFLD and cardiac dysfunction in children.

scholarly journals The Role of Oxidative Stress in NAFLD–NASH–HCC Transition—Focus on NADPH Oxidases

Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 687
Author(s):  
Daniela Gabbia ◽  
Luana Cannella ◽  
Sara De De Martin
Keyword(s):  
Oxidative Stress ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Current Knowledge ◽  
Mechanisms Of Action ◽  
Nadph Oxidases ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

A peculiar role for oxidative stress in non-alcoholic fatty liver disease (NAFLD) and its transition to the inflammatory complication non-alcoholic steatohepatitis (NASH), as well as in its threatening evolution to hepatocellular carcinoma (HCC), is supported by numerous experimental and clinical studies. NADPH oxidases (NOXs) are enzymes producing reactive oxygen species (ROS), whose abundance in liver cells is closely related to inflammation and immune responses. Here, we reviewed recent findings regarding this topic, focusing on the role of NOXs in the different stages of fatty liver disease and describing the current knowledge about their mechanisms of action. We conclude that, although there is a consensus that NOX-produced ROS are toxic in non-neoplastic conditions due to their role in the inflammatory vicious cycle sustaining the transition of NAFLD to NASH, their effect is controversial in the neoplastic transition towards HCC. In this regard, there are indications of a differential effect of NOX isoforms, since NOX1 and NOX2 play a detrimental role, whereas increased NOX4 expression appears to be correlated with better HCC prognosis in some studies. Further studies are needed to fully unravel the mechanisms of action of NOXs and their relationships with the signaling pathways modulating steatosis and liver cancer development.

scholarly journals Prevalence and Predictor of Nonalcoholic Steatohepatitis (NASH) in Nonalcoholic Fatty Liver Disease (NAFLD)

2015 ◽  
Vol 32 (2) ◽  
pp. 71-77 ◽  
Author(s):  
Shahinul Alam ◽  
Mahabubul Alam ◽  
Sheikh Mohammad Noor E Alam ◽  
Ziaur Rahman Chowdhury ◽  
Jahangir Kabir
Keyword(s):  
Metabolic Syndrome ◽  
Liver Disease ◽  
Liver Biopsy ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Resistance Index ◽  
Histopathological Study ◽  
Alcoholic Fatty Liver ◽  
Nonalcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Fatty liver is a common cause of chronic liver disease in developed as well as developing countries.We have designed this study to estimate the prevalence and predictors for non alcoholic steatohepatitis (NASH) in non alcoholic fatty liver disease (NAFLD). We have included 493 patients with sonographic evidence of fatty change in liver and 177 of them had done liver biopsy for histopathological study. Other causes of liver disease and alcohol consumption were excluded. Metabolic syndrome and biochemical and anthropometric evaluation was done. Females were predominating 250 (57.0 %). Centrally obese 422 (96.2 %) was more than over all obesity330 (75.1%). NASH was absent in 10 (5.6%) cases and diagnostic of NASH was 75 Journal of Bangladesh College of Physicians and Surgeons Vol. 32, No. 2, April 2014 (42.4 %).Presence of diabetes could significantly (p = 0.001) predicted NASH. Age, sex, BMI, waist circumference, Serum HDL,triglyceride, insulin resistance index, hypertension, metabolic syndrome could not predict NASH. Serum GGT level was significantly (p = 0.05) higher in NASHwith a sensitivity of 45 % and specificity of 68 % only. Serum ALT and AST level could not detect NASH. Females were predominant sufferer of NAFLD in Bangladesh. Prevalence of NASH was much higher42.4%. Diabetes was the main predictor of NASH. GGT was the only biochemical indicator of NASH. We recommend liver biopsy in NAFLD with diabetes and raised GGT.J Bangladesh Coll Phys Surg 2014; 32: 71-77

scholarly journals 5-Bis-(2,6-difluoro-benzylidene) Cyclopentanone Acts as a Selective 11β-Hydroxysteroid Dehydrogenase one Inhibitor to Treat Diet-Induced Nonalcoholic Fatty Liver Disease in Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Hongguo Guan ◽  
Yiyan Wang ◽  
Huitao Li ◽  
Qiqi Zhu ◽  
Xiaoheng Li ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Serum Insulin ◽  
Hydroxysteroid Dehydrogenase ◽  
Biologically Active ◽  
Alcoholic Fatty Liver ◽  
Nonalcoholic Fatty Liver ◽  
Low Concentration

Background: 11β-Hydroxysteroid dehydrogenase one is responsible for activating inert glucocorticoid cortisone into biologically active cortisol in humans and may be a novel target for the treatment of nonalcoholic fatty liver disease.Methods: A series of benzylidene cyclopentanone derivatives were synthesized, and the selective inhibitory effects on rat, mouse and human 11β-hydroxysteroid dehydrogenase one and two were screened. The most potent compound [5-bis-(2,6-difluoro-benzylidene)-cyclopentanone] (WZS08), was used to treat nonalcoholic fatty liver disease in mice fed a high-fat-diet for 100 days.Results: WZS08 was the most potent inhibitor of rat, mouse, and human 11β-hydroxysteroid dehydrogenase 1, with half maximum inhibitory concentrations of 378.0, 244.1, and 621.1 nM, respectively, and it did not affect 11β-hydroxysteroid dehydrogenase two at 100 μM. When mice were fed WZS08 (1, 2, and 4 mg/kg) for 100 days, WZS08 significantly lowered the serum insulin levels and insulin index at 4 mg/kg. WZS08 significantly reduced the levels of serum triglycerides, cholesterol, low-density lipoprotein, and hepatic fat ratio at low concentration of 1 mg/kg. It down-regulated Plin2 expression and up-regulated Fabp4 expression at low concentration of 1 mg/kg. It significantly improved the morphology of the non-alcoholic fatty liver.Conclusion: WZS08 selectively inhibits rat, mouse, and human 11β-hydroxysteroid dehydrogenase 1, and can treat non-alcoholic fatty liver disease in a mouse model.

Abstract 454: High Density Lipoprotein Proteome Dynamics is Altered in Non-alcoholic Fatty Liver Disease

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Takhar Kasumov
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Oxidase Activity ◽  
Fatty Liver Disease ◽  
Metabolic Labeling ◽  
Alcoholic Fatty Liver ◽  
Nonalcoholic Fatty Liver ◽  
Inflammatory Index ◽  
Complement 3 ◽  
Hdl Dysfunction

Objectives: Nonalcoholic fatty liver disease (NAFLD) is associated with an increased rate of cardiovascular disease (CVD) related mortality. HDL protects against CVD through reverse cholesterol transport, anti-oxidant and anti-inflammatory functions. HDL functions and the proteome composition are altered in CVD. We used 2 H 2 O metabolic labeling approach to test hypothesis that altered HDL proteome dynamics is involved in HDL dysfunction in NAFLD. Methods: The kinetics of HDL proteins were measured in patients NAFLD (n=12) and healthy controls (n=8). Each subject consumed 2 H 2 O in their drinking water and blood samples were collected at different time points during one week. 2 H-enrichment of tryptic peptides from HDL proteins were analyzed by mass spectrometry. Oxidase activity of HDL-associated ceruloplasmin (Cp) and HDL’s inflammatory index were quantified using spectrophotometric assays. Results: Compared to control, NAFLD had higher BMI, Hba1c, HOMA-IR, plasma AST, ALT and triglycerides, but similar LDL and HDL cholesterol. NAFLD also had higher inflammatory index (1.8±0.5 vs 1.2±0.2 RUF/mgHDLc/min, p<0.05) and oxidase activity of Cp (93.7±61.2 vs 61.2 U/L, p<0.005). This was associated with increased serum actvity of MPO (6.2±1.2 vs 8.4±1.6, p<0.05), a nutrophile-derived protein involved in HDL dysfunction. HDL NAFLD was significantly enriched with proteins involved in the acute phase response (complement 3, Cp) but depleted in apoAII and PON1. These changes were associated with increased fractional catabolic rates (FCRs) of apoAI (1.6±0.2 vs 1.1±0.3 %/h), apoAII (1.6±0.2 vs 1.1±0.3 %/h), apoAIV (2.6±0.8 vs 3.9±0.7%/h) and increased relative production rate (RPR) of complement 3 (>4 fold). Oxidase activity of Cp was positively associated with FCR of apoAI (r=0.53, p=0.002) and RPR of C3 (r=0.32, p=0.03). Conclusions: HDL dysfunction in NASH could be related to the altered turnover of HDL proteins, including increased degradation of apoAI, apoAII, apoAIV and increased production of C3.

scholarly journals Diagnostic Accuracy of Serological Markers in Viral Hepatitis and Non Alcoholic Fatty Liver Disease. A Comparative Study in Tertiary Care Hospital of Western Nepal

1970 ◽  
Vol 1 (2) ◽  
pp. 60-63
Author(s):  
Ankush Mittal ◽  
Brijesh Sathian ◽  
Nishida Chandrasekharan ◽  
Akshay Lekhi ◽  
Shamim Mohammad Farooqui ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Viral Hepatitis ◽  
Fatty Liver Disease ◽  
Liver Diseases ◽  
Serological Markers ◽  
Alcoholic Fatty Liver ◽  
Nonalcoholic Fatty Liver ◽  
Non Invasive ◽  
Alcoholic Fatty Liver Disease

Background: Liver diseases is apparently increasing and emerging as a major public health problem. Worldwide,  chronic hepatitis B has  become  the tenth leading cause of death  and  persons infected with chronic hepatitis B virus (HBV) and hepatitis C virus (HCV), are about 350 million and  125 million respectively. The aim of current retrospective comparative study was concerned primarily to evaluate the significance of non invasive serological markers for diagnosing liver diseases and their predictive implications in Pokhara valley. Materials and Methods: It was a hospital based retrospective study carried out using the data maintained in the Department of Biochemistry of the Manipal Teaching Hospital, Pokhara, Nepal between 1st June 2009 and 31st   October 2010.  The variables collected were total protein, albumin, AST, ALT, total bilirubin, direct bilirubin.  Descriptive statistics and testing of hypothesis were used for the analysis. Data was analyzed using EPI INFO and SPSS 16 software. Results: Of 515 subjects, 120 were suffering from viral hepatitis and 88 had non alcoholic fatty liver disease. In cases of viral hepatitis, mean values of AST (CI 730.65 to 902.68) and ALT (CI 648.14 to 847.59) were markedly increased as compared to controls. Mild to moderate elevations in serum levels of aspartate aminotransferase (CI 43.42 to 49.49), alanine aminotransferase (CI 43.90 to 53.92) were the most common laboratory abnormalities found in patients with nonalcoholic fatty liver disease. Conclusion: Non invasive tests have demonstrated a reasonable ability to identify significant fibrosis, cirrhosis in particular, nor is it surprising that liver disease specialists and patients favour a non invasive approach.Key words: Viral hepatitis; Nonalcoholic fatty liver disease; Nepal.DOI: http://dx.doi.org/10.3126/nje.v1i2.5137 Nepal Journal of Epidemiology 2011;1 (2):60-63

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