The Role of Oxidative Stress in Non-Alcoholic Fatty Liver Disease

A special issue of Antioxidants (ISSN 2076-3921). This special issue belongs to the section "Health Outcomes of Antioxidants and Oxidative Stress".

Deadline for manuscript submissions: closed (30 April 2024) | Viewed by 11033

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Institute of Oriental Medicine, Dongguk University, 32, Dongguk-ro, Goyang 10326, Gyeonggi-do, Republic of Korea
Interests: functional dyspepsia; gut microbiota; herbal medicine; gastrointestinal diseases
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Special Issue Information

Dear Colleagues,

With the rapid increase in prevalence and the lack of effective therapeutics, Non-Alcoholic Fatty Liver Disease (NAFLD) directly impacts approximately one-fourth of the global population and is gradually becoming a serious issue. While the precise pathogenesis of NAFLD is still not fully understood, it is widely believed to involve a complex interplay with genetic and various environmental factors. As is well known, excessive oxidative stress can significantly accelerate the progression of the NAFLD by inducing lipid peroxidation, mitochondrial dysfunction, inflammation, endoplasmic reticulum stress, and other related factors. However, there remains a notable gap in extensive research regarding how diverse environmental factors impact the progression of NAFLD through oxidative stress, like gut microbiota, lifestyle, food and beverage, and mental stress. Therefore, this Special Issue, entitled 'The Role of Oxidative Stress in Non-Alcoholic Fatty Liver Disease', aims to select contributions on the advances in research on oxidative stress and its association with NAFLD. We welcome the submission of original research and review articles addressing etiology, mechanism, diagnosis, treatment, prevention, and prognosis of NAFLD, with a specific focus on oxidative stress. We look forward to your valuable contributions.

Potential topics include, but are not limited to:

  1. Exploring the interaction mechanism between oxidative stress and NAFLD;
  2. Studying how antioxidants attenuate NAFLD in relation to oxidative stress;
  3. Future perspectives for novel antioxidant-associated strategy for NAFLD;
  4. Considering the potential of personalized therapies and diagnostics based on the status of oxidative stress.

Dr. Jinghua Wang
Dr. Jayanta Kumar Patra
Guest Editors

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Keywords

  • antioxidant
  • oxidative stress
  • NAFLD
  • MASLD
  • F&B
  • gut microbiota
  • lifestyle

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Published Papers (5 papers)

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Research

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20 pages, 5721 KiB  
Article
Dramatic Suppression of Lipogenesis and No Increase in Beta-Oxidation Gene Expression Are among the Key Effects of Bergamot Flavonoids in Fatty Liver Disease
by Maddalena Parafati, Daniele La Russa, Antonella Lascala, Francesco Crupi, Concetta Riillo, Bartosz Fotschki, Vincenzo Mollace and Elzbieta Janda
Antioxidants 2024, 13(7), 766; https://doi.org/10.3390/antiox13070766 - 25 Jun 2024
Viewed by 1482
Abstract
Bergamot flavonoids have been shown to prevent metabolic syndrome, non-alcoholic fatty liver disease (NAFLD) and stimulate autophagy in animal models and patients. To investigate further the mechanism of polyphenol-dependent effects, we performed a RT2-PCR array analysis on 168 metabolism, transport and autophagy-related genes [...] Read more.
Bergamot flavonoids have been shown to prevent metabolic syndrome, non-alcoholic fatty liver disease (NAFLD) and stimulate autophagy in animal models and patients. To investigate further the mechanism of polyphenol-dependent effects, we performed a RT2-PCR array analysis on 168 metabolism, transport and autophagy-related genes expressed in rat livers exposed for 14 weeks to different diets: standard, cafeteria (CAF) and CAF diet supplemented with 50 mg/kg of bergamot polyphenol fraction (BPF). CAF diet caused a strong upregulation of gluconeogenesis pathway (Gck, Pck2) and a moderate (>1.7 fold) induction of genes regulating lipogenesis (Srebf1, Pparg, Xbp1), lipid and cholesterol transport or lipolysis (Fabp3, Apoa1, Lpl) and inflammation (Il6, Il10, Tnf). However, only one β-oxidation gene (Cpt1a) and a few autophagy genes were differentially expressed in CAF rats compared to controls. While most of these transcripts were significantly modulated by BPF, we observed a particularly potent effect on lipogenesis genes, like Acly, Acaca and Fasn, which were suppressed far below the mRNA levels of control livers as confirmed by alternative primers-based RT2-PCR analysis and western blotting. These effects were accompanied by downregulation of pro-inflammatory cytokines (Il6, Tnfa, and Il10) and diabetes-related genes. Few autophagy (Map1Lc3a, Dapk) and no β-oxidation gene expression changes were observed compared to CAF group. In conclusion, chronic BPF supplementation efficiently prevents NAFLD by modulating hepatic energy metabolism and inflammation gene expression programs, with no effect on β-oxidation, but profound suppression of de novo lipogenesis. Full article
(This article belongs to the Special Issue The Role of Oxidative Stress in Non-Alcoholic Fatty Liver Disease)
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16 pages, 1122 KiB  
Article
Impact of Adherence to the Mediterranean Diet on Antioxidant Status and Metabolic Parameters in NAFLD Patients: A 24-Month Lifestyle Intervention Study
by Maria Magdalena Quetglas-Llabrés, Margalida Monserrat-Mesquida, Cristina Bouzas, Silvia García, Emma Argelich, Miguel Casares, Lucía Ugarriza, Isabel Llompart, Josep A. Tur and Antoni Sureda
Antioxidants 2024, 13(4), 480; https://doi.org/10.3390/antiox13040480 - 17 Apr 2024
Cited by 3 | Viewed by 1569
Abstract
Background: The Mediterranean Diet (MedDiet) is recognized as a healthy dietary pattern. Non-alcoholic fatty liver disease (NAFLD) is characterized by the excessive accumulation of fat in the liver. Objectives: To assess the antioxidant status in erythrocytes, plasma, and peripheral blood mononuclear cells (PBMCs) [...] Read more.
Background: The Mediterranean Diet (MedDiet) is recognized as a healthy dietary pattern. Non-alcoholic fatty liver disease (NAFLD) is characterized by the excessive accumulation of fat in the liver. Objectives: To assess the antioxidant status in erythrocytes, plasma, and peripheral blood mononuclear cells (PBMCs) of NAFLD patients following a 24-month lifestyle intervention based on the MedDiet. Adult patients (n = 40; aged 40–60 years) diagnosed with NAFLD by magnetic resonance imaging were divided into two groups based on their adherence to the MedDiet. Consumption was assessed using a validated 143-item semiquantitative Food Frequency Questionnaire. Anthropometrics, biochemistry parameters, intrahepatic fat contents (IFC), antioxidants, and inflammatory biomarkers were measured in plasma and erythrocytes before and after the intervention. Results: After the intervention, body mass index (BMI) and plasma levels of total cholesterol, low-density lipoprotein cholesterol (LDL-chol), triglycerides, malondialdehyde (MDA), and cytokeratin-18 (CK18) decreased, and high-density lipoprotein cholesterol (HDL-chol) increased. Participants with high adherence to MedDiet showed lower IFC, hepatic enzyme (AST, ALT, and GGT), glycemia, oxidase LDL (oxLDL) plasma levels, and erythrocyte MDA levels. Higher antioxidant activity (erythrocyte catalase-CAT, superoxide dismutase-SOD, glutathione peroxidase-GPx, glutathione reductase-GRd, and total glutathione-GSH as well as PBMCs-CAT gene expression) was observed in these patients, along with a reduction of PBMCs reactive oxygen species production and Toll-like receptor 4 (TLR4) expression. Inverse associations were observed between adherence to the MedDiet and BMI, glycemia, AST, IFC, and CK18 plasma levels and oxLDL, CAT, SOD, and GRd activities in erythrocytes. A significant linear regression was observed between adherence to the MedDiet and antioxidant score. Conclusions: Adherence to the MedDiet is associated with improved plasma and PBMC antioxidant and inflammatory biomarker profiles and high antioxidant defences in erythrocytes. Full article
(This article belongs to the Special Issue The Role of Oxidative Stress in Non-Alcoholic Fatty Liver Disease)
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23 pages, 11869 KiB  
Article
Effect of Gracilaria vermiculophylla Macroalga on Non-Alcoholic Fatty Liver Disease in Obese Rats
by Maitane González-Arceo, Leixuri Aguirre, María Teresa Macarulla, Clàudia Gil-Pitarch, María Luz Martínez-Chantar, María P. Portillo and Saioa Gómez-Zorita
Antioxidants 2024, 13(3), 369; https://doi.org/10.3390/antiox13030369 - 18 Mar 2024
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Abstract
Marine algae are valuable sources of bioactive compounds that have the potential to be used in the management of various pathologies. Despite the increasing prevalence of NAFLD, the absence of an approved effective pharmacological treatment with demonstrable effectiveness persists. In this context, the [...] Read more.
Marine algae are valuable sources of bioactive compounds that have the potential to be used in the management of various pathologies. Despite the increasing prevalence of NAFLD, the absence of an approved effective pharmacological treatment with demonstrable effectiveness persists. In this context, the aim of the present study is to assess the effect of Gracilaria vermiculophylla red seaweed dietary supplementation on hepatic lipid accumulation, as well as on oxidative stress, inflammation and fibrosis- related markers on obese fa/fa Zucker rats fed with a standard diet, supplemented or not with 2.5% or 5% dehydrated Gracilaria vermiculophylla. After a six-week supplementation with the macroalga, no significant reduction in hepatic total lipid content or hepatic triglyceride content was observed. However, both doses were able to diminish hepatic NEFA concentration by reducing de novo lipogenesis and increasing mitochondrial biogenesis. Moreover, supplementation with the dose of 2.5% improved some oxidative stress and inflammation-related markers. Supplementation with the dose of 5% did not exert these clear beneficial effects. Thus, this study demonstrates that while Gracilaria vermiculophylla may not mitigate hepatic steatosis, it could exert protective effects on the liver by reducing NEFA content and enhancing oxidative stress and inflammation parameters. Full article
(This article belongs to the Special Issue The Role of Oxidative Stress in Non-Alcoholic Fatty Liver Disease)
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Review

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29 pages, 1227 KiB  
Review
Oxidative Stress as a Target for Non-Pharmacological Intervention in MAFLD: Could There Be a Role for EVOO?
by Aurelio Seidita, Alessandra Cusimano, Alessandra Giuliano, Maria Meli, Antonio Carroccio, Maurizio Soresi and Lydia Giannitrapani
Antioxidants 2024, 13(6), 731; https://doi.org/10.3390/antiox13060731 - 16 Jun 2024
Cited by 1 | Viewed by 1875
Abstract
Oxidative stress plays a central role in most chronic liver diseases and, in particular, in metabolic dysfunction-associated fatty liver disease (MAFLD), the new definition of an old condition known as non-alcoholic fatty liver disease (NAFLD). The mechanisms leading to hepatocellular fat accumulation in [...] Read more.
Oxidative stress plays a central role in most chronic liver diseases and, in particular, in metabolic dysfunction-associated fatty liver disease (MAFLD), the new definition of an old condition known as non-alcoholic fatty liver disease (NAFLD). The mechanisms leading to hepatocellular fat accumulation in genetically predisposed individuals who adopt a sedentary lifestyle and consume an obesogenic diet progress through mitochondrial and endoplasmic reticulum dysfunction, which amplifies reactive oxygen species (ROS) production, lipid peroxidation, malondialdehyde (MDA) formation, and influence the release of chronic inflammation and liver damage biomarkers, such as pro-inflammatory cytokines. This close pathogenetic link has been a key stimulus in the search for therapeutic approaches targeting oxidative stress to treat steatosis, and a number of clinical trials have been conducted to date on subjects with NAFLD using drugs as well as supplements or nutraceutical products. Vitamin E, Vitamin D, and Silybin are the most studied substances, but several non-pharmacological approaches have also been explored, especially lifestyle and diet modifications. Among the dietary approaches, the Mediterranean Diet (MD) seems to be the most reliable for affecting liver steatosis, probably with the added value of the presence of extra virgin olive oil (EVOO), a healthy food with a high content of monounsaturated fatty acids, especially oleic acid, and variable concentrations of phenols (oleocanthal) and phenolic alcohols, such as hydroxytyrosol (HT) and tyrosol (Tyr). In this review, we focus on non-pharmacological interventions in MAFLD treatment that target oxidative stress and, in particular, on the role of EVOO as one of the main antioxidant components of the MD. Full article
(This article belongs to the Special Issue The Role of Oxidative Stress in Non-Alcoholic Fatty Liver Disease)
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20 pages, 1360 KiB  
Review
Roles of Traditional and Next-Generation Probiotics on Non-Alcoholic Fatty Liver Disease (NAFLD) and Non-Alcoholic Steatohepatitis (NASH): A Systematic Review and Network Meta-Analysis
by Yuezhi Zhu, Jen Kit Tan, Jia Liu and Jo Aan Goon
Antioxidants 2024, 13(3), 329; https://doi.org/10.3390/antiox13030329 - 7 Mar 2024
Cited by 3 | Viewed by 3375
Abstract
Non-alcoholic fatty liver disease (NAFLD) and its progressive stage, non-alcoholic steatohepatitis (NASH), are becoming one of the most common chronic liver diseases globally. Lifestyle interventions such as weight reduction, increased physical activity, and maintaining healthy diets play a pivotal role in managing NAFLD/NASH. [...] Read more.
Non-alcoholic fatty liver disease (NAFLD) and its progressive stage, non-alcoholic steatohepatitis (NASH), are becoming one of the most common chronic liver diseases globally. Lifestyle interventions such as weight reduction, increased physical activity, and maintaining healthy diets play a pivotal role in managing NAFLD/NASH. Recent studies suggest that the gut microbiome is associated with the pathogenesis of NAFLD/NASH, prompting microbiome-targeted therapy to emerge as a new therapeutic option for NAFLD/NASH. We conducted a systematic review based on the PRISMA statement and employed network meta-analysis to investigate the effects of traditional probiotics and next-generation probiotics (NGPs) on NAFLD/NASH. Comparative analysis reveals that traditional probiotics primarily reduce liver fat deposition and inflammation by improving gut microbiota composition, enhancing intestinal barrier function, and modulating immune responses. In contrast, NGPs demonstrate a more significant therapeutic potential, attributed to their direct effects on inhibiting oxidative stress and their ability to enhance the production of short-chain fatty acids (SCFAs), NGPs appear as a new potential strategy for the management of NAFLD/NASH through their dual action of directly inhibiting oxidative stress and enhancing SCFA production, highlighting the importance of understanding and utilizing the direct and indirect regulatory mechanisms of oxidative stress in the management of NAFLD/NASH. Full article
(This article belongs to the Special Issue The Role of Oxidative Stress in Non-Alcoholic Fatty Liver Disease)
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