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Nutrition and Non-alcoholic Fatty Liver Disease: Gene Storm

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A special issue of Nutrients (ISSN 2072-6643). This special issue belongs to the section "Nutrigenetics and Nutrigenomics".

Deadline for manuscript submissions: closed (15 October 2021) | Viewed by 37512

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Special Issue Editors

Dr. Marcello Dallio

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Guest Editor

Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, Via S. Pansini 5, 80131, Naples, Italy
Interests: non-alcoholic liver disease; metabolic syndrome; alcoholic liver disease; viral hepatitis; hepatocellular carcinoma; liver cirrhosis; trained immunity; gut microbiota

Prof. Dr. Carmelina Loguercio

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Guest Editor

Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, Via S. Pansini 5, 80131, Naples, Italy
Interests: alcoholic liver disease; hepatic encephalopathy; liver cirrhosis; acute liver failure; gut microbiota; oxidative stress

Special Issue Information

Non-alcoholic fatty liver disease (NAFLD) has already became the most common liver disease worldwide, and its prevalence is still increasing, showing faster evolution to more advanced stages as well as the development of hepatic and extrahepatic complications. Recently, genome-wide association studies have made it possible to uncover the main common genetic determinants of NAFLD pathogenesis and progression. In this context, lifestyle aspects such as nutrition and physical activity represent major key factors to prevent and manage NAFLD.

Nutritional habit modifications, in terms of overall energy balance, diet macro and micronutrients composition, and quality, have shown an important therapeutic role. Recently, the interest in nutraceutical compounds has increased, and the scientific literature reports an inverse association between the consumption of nutrients rich in antioxidants and the risk of NAFLD development and mortality. The interplay between genes and nutrients in this context seems to have a crucial role in the comprehension of the NAFLD pathological picture and may help to identify new therapeutic possibilities.

We invite clinicians and researchers to submit original articles and reviews to this Special Issue of Nutrients entitled “Nutrition and Non-Alcoholic Fatty Liver Disease: Gene Storm”.

We look forward to your valuable contributions.

Dr. Marcello Dallio
Prof. Dr. Carmelina Loguercio
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Nutrients is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

Non-alcoholic fatty liver disease
Nutrigenomics
Metabolomics
Oxidative stress
Metabolic syndrome
Nutraceuticals
High-fat diet
Fructose-enriched foods

Published Papers (6 papers)

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Research

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18 pages, 2541 KiB

Open AccessArticle

The Combination of Berberine, Tocotrienols and Coffee Extracts Improves Metabolic Profile and Liver Steatosis by the Modulation of Gut Microbiota and Hepatic miR-122 and miR-34a Expression in Mice

by Valentina Cossiga, Vincenzo Lembo, Cecilia Nigro, Paola Mirra, Claudia Miele, Valeria D’Argenio, Alessia Leone, Giovanna Mazzone, Iolanda Veneruso, Maria Guido, Francesco Beguinot, Nicola Caporaso and Filomena Morisco

Nutrients 2021, 13(4), 1281; https://doi.org/10.3390/nu13041281 - 13 Apr 2021

Cited by 16 | Viewed by 3303

Abstract

Non-alcoholic-fatty liver disease (NAFLD) is spreading worldwide. Specific drugs for NAFLD are not yet available, even if some plant extracts show beneficial properties. We evaluated the effects of a combination, composed by Berberis Aristata, Elaeis Guineensis and Coffea Canephora, on the development of obesity, hepatic steatosis, insulin-resistance and on the modulation of hepatic microRNAs (miRNA) levels and microbiota composition in a mouse model of liver damage. C57BL/6 mice were fed with standard diet (SD, n = 8), high fat diet (HFD, n = 8) or HFD plus plant extracts (HFD+E, n = 8) for 24 weeks. Liver expression of miR-122 and miR-34a was evaluated by quantitativePCR. Microbiome analysis was performed on cecal content by 16S rRNA sequencing. HFD+E-mice showed lower body weight (p < 0.01), amelioration of insulin-sensitivity (p = 0.021), total cholesterol (p = 0.014), low-density-lipoprotein-cholesterol (p < 0.001), alanine-aminotransferase (p = 0.038) and hepatic steatosis compared to HFD-mice. While a decrease of hepatic miR-122 and increase of miR-34a were observed in HFD-mice compared to SD-mice, both these miRNAs had similar levels to SD-mice in HFD+E-mice. Moreover, a different microbial composition was found between SD- and HFD-mice, with a partial rescue of dysbiosis in HFD+E-mice. This combination of plant extracts had a beneficial effect on HFD-induced NAFLD by the modulation of miR-122, miR-34a and gut microbiome. Full article

(This article belongs to the Special Issue Nutrition and Non-alcoholic Fatty Liver Disease: Gene Storm)

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13 pages, 2512 KiB

Open AccessArticle

A Novel Nutraceuticals Mixture Improves Liver Steatosis by Preventing Oxidative Stress and Mitochondrial Dysfunction in a NAFLD Model

by Moris Sangineto, Vidyasagar Naik Bukke, Francesco Bellanti, Rosanna Tamborra, Archana Moola, Loren Duda, Rosanna Villani, Antonino Davide Romano and Gaetano Serviddio

Nutrients 2021, 13(2), 652; https://doi.org/10.3390/nu13020652 - 17 Feb 2021

Cited by 18 | Viewed by 3289

Abstract

Non-alcoholic fatty liver disease (NAFLD) is the leading cause of liver disease globally, and represents a health care burden as treatment options are very scarce. The reason behind the NAFLD progression to non-alcoholic steatohepatitis (NASH) is not completely understood. Recently, the deficiency of micronutrients (e.g., vitamins, minerals, and other elements) has been suggested as crucial in NAFLD progression, such that recent studies reported the potential hepatic antioxidant properties of micronutrients supplementation. However, very little is known. Here we have explored the potential beneficial effects of dietary supplementation with FLINAX, a novel mixture of nutraceuticals (i.e., vitamin E, vitamin D3, olive dry-extract, cinnamon dry-extract and fish oil) in a NAFLD model characterized by oxidative stress and mitochondrial function impairment. Steatosis was firstly induced in Wistar rats by feeding with a high-fat/high-cholesterol diet for 4 weeks, and following this the rats were divided into two groups. One group (n = 8) was treated for 2 weeks with a normal chow-diet, while a second group (n = 8) was fed with a chow-diet supplemented with 2% FLINAX. Along with the entire experiment (6 weeks), a third group of rats was fed with a chow-diet only as control. Statistical analysis was performed with Student’s T test or one-way ANOVA followed by post-hoc Bonferroni test when appropriate. Steatosis, oxidative stress and mitochondrial respiratory chain (RC) complexes activity were analyzed in liver tissues. The dietary supplementation with FLINAX significantly improved hepatic steatosis and lipid accumulation compared to untreated rats. The mRNA and protein levels analysis showed that CPT1A and CPT2 were up-regulated by FLINAX, suggesting the enhancement of fatty acids oxidation (FAO). Important lipoperoxidation markers (i.e., HNE- and MDA-protein adducts) and the quantity of total mitochondrial oxidized proteins were significantly lower in FLINAX-treated rats. Intriguingly, FLINAX restored the mitochondrial function, stimulating the activity of mitochondrial RC complexes (i.e., I, II, III and ATP-synthase) and counteracting the peroxide production from pyruvate/malate (complex I) and succinate (complex II). Therefore, the supplementation with FLINAX reprogrammed the cellular energy homeostasis by restoring the efficiency of mitochondrial function, with a consequent improvement in steatosis. Full article

(This article belongs to the Special Issue Nutrition and Non-alcoholic Fatty Liver Disease: Gene Storm)

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Review

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28 pages, 1510 KiB

Open AccessReview

Nutrigenomics and Nutrigenetics in Metabolic- (Dysfunction) Associated Fatty Liver Disease: Novel Insights and Future Perspectives

by Marcello Dallio, Mario Romeo, Antonietta Gerarda Gravina, Mario Masarone, Tiziana Larussa, Ludovico Abenavoli, Marcello Persico, Carmelina Loguercio and Alessandro Federico

Nutrients 2021, 13(5), 1679; https://doi.org/10.3390/nu13051679 - 15 May 2021

Cited by 12 | Viewed by 6919

Abstract

Metabolic- (dysfunction) associated fatty liver disease (MAFLD) represents the predominant hepatopathy and one of the most important systemic, metabolic-related disorders all over the world associated with severe medical and socio-economic repercussions due to its growing prevalence, clinical course (steatohepatitis and/or hepatocellular-carcinoma), and related extra-hepatic comorbidities. To date, no specific medications for the treatment of this condition exist, and the most valid recommendation for patients remains lifestyle change. MAFLD has been associated with metabolic syndrome; its development and progression are widely influenced by the interplay between genetic, environmental, and nutritional factors. Nutrigenetics and nutrigenomics findings suggest nutrition’s capability, by acting on the individual genetic background and modifying the specific epigenetic expression as well, to influence patients’ clinical outcome. Besides, immunity response is emerging as pivotal in this multifactorial scenario, suggesting the interaction between diet, genetics, and immunity as another tangled network that needs to be explored. The present review describes the genetic background contribution to MAFLD onset and worsening, its possibility to be influenced by nutritional habits, and the interplay between nutrients and immunity as one of the most promising research fields of the future in this context. Full article

(This article belongs to the Special Issue Nutrition and Non-alcoholic Fatty Liver Disease: Gene Storm)

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19 pages, 4323 KiB

Open AccessReview

The Role of Fructose in Non-Alcoholic Steatohepatitis: Old Relationship and New Insights

by Alessandro Federico, Valerio Rosato, Mario Masarone, Pietro Torre, Marcello Dallio, Mario Romeo and Marcello Persico

Nutrients 2021, 13(4), 1314; https://doi.org/10.3390/nu13041314 - 16 Apr 2021

Cited by 38 | Viewed by 9764

Abstract

Non-alcoholic fatty liver disease (NAFLD) represents the result of hepatic fat overload not due to alcohol consumption and potentially evolving to advanced fibrosis, cirrhosis, and hepatocellular carcinoma. Fructose is a naturally occurring simple sugar widely used in food industry linked to glucose to form sucrose, largely contained in hypercaloric food and beverages. An increasing amount of evidence in scientific literature highlighted a detrimental effect of dietary fructose consumption on metabolic disorders such as insulin resistance, obesity, hepatic steatosis, and NAFLD-related fibrosis as well. An excessive fructose consumption has been associated with NAFLD development and progression to more clinically severe phenotypes by exerting various toxic effects, including increased fatty acid production, oxidative stress, and worsening insulin resistance. Furthermore, some studies in this context demonstrated even a crucial role in liver cancer progression. Despite this compelling evidence, the molecular mechanisms by which fructose elicits those effects on liver metabolism remain unclear. Emerging data suggest that dietary fructose may directly alter the expression of genes involved in lipid metabolism, including those that increase hepatic fat accumulation or reduce hepatic fat removal. This review aimed to summarize the current understanding of fructose metabolism on NAFLD pathogenesis and progression. Full article

(This article belongs to the Special Issue Nutrition and Non-alcoholic Fatty Liver Disease: Gene Storm)

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23 pages, 975 KiB

Open AccessReview

The Role of Resveratrol in Liver Disease: A Comprehensive Review from In Vitro to Clinical Trials

by Carmine Izzo, Monica Annunziata, Giuseppe Melara, Roberta Sciorio, Marcello Dallio, Mario Masarone, Alessandro Federico and Marcello Persico

Nutrients 2021, 13(3), 933; https://doi.org/10.3390/nu13030933 - 13 Mar 2021

Cited by 54 | Viewed by 6759

Abstract

Many studies have shown that resveratrol has a lot of therapeutic effects on liver disorders. Its administration can significantly increase the survival rate after liver transplantation, reduce fat deposition and ischemia-induced necrosis and apoptosis in Wistar rats. Resveratrol can provide Liver protection against chemical, cholestatic, and alcohol-mediated damage. It can improve glucose metabolism and lipid profile, reduce liver fibrosis, and steatosis. Additionally, it is capable of altering the fatty acid composition of the liver cells. Resveratrol may be a potential treatment option for the management of non-alcoholic fatty liver disease (NAFLD) due to its anti-inflammatory, antioxidant, and calorie-restricting effects. There are also studies that have evaluated the effect of resveratrol on lipid and liver enzyme profiles among patients with metabolic syndrome (MetS) and related disorders. Based on the extent of liver disease worldwide and the need to find new treatment possibilities, this review critically examines current in vitro and in vivo preclinical studies and human clinical studies related to liver protection. Full article

(This article belongs to the Special Issue Nutrition and Non-alcoholic Fatty Liver Disease: Gene Storm)

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10 pages, 893 KiB

Open AccessEditor’s ChoiceReview

Dietary Polyphenols and Non-Alcoholic Fatty Liver Disease

by Ludovico Abenavoli, Tiziana Larussa, Alessandro Corea, Anna Caterina Procopio, Luigi Boccuto, Marcello Dallio, Alessandro Federico and Francesco Luzza

Nutrients 2021, 13(2), 494; https://doi.org/10.3390/nu13020494 - 3 Feb 2021

Cited by 72 | Viewed by 6219

Abstract

Non-alcoholic fatty liver disease (NAFLD), which is emerging as a major public health issue worldwide, is characterized by a wide spectrum of liver disorders, ranging from simple fat accumulation in hepatocytes, also known as steatosis, to non-alcoholic steatohepatitis (NASH) and cirrhosis. At present, the pharmacological treatment of NAFLD is still debated and dietary strategies for the prevention and the treatment of this condition are strongly considered. Polyphenols are a group of plant-derived compounds whose anti-inflammatory and antioxidant properties are associated with a low prevalence of metabolic diseases, including obesity, hypertension, and insulin resistance. Since inflammation and oxidative stress are the main risk factors involved in the pathogenesis of NAFLD, recent studies suggest that the consumption of polyphenol-rich diets is involved in the prevention and treatment of NAFLD. However, few clinical trials are available on human subjects with NAFLD. Here, we reviewed the emerging existing evidence on the potential use of polyphenols to treat NAFLD. After introducing the physiopathology of NAFLD, we focused on the most investigated phenolic compounds in the setting of NAFLD and described their potential benefits, starting from basic science studies to animal models and human trials. Full article

(This article belongs to the Special Issue Nutrition and Non-alcoholic Fatty Liver Disease: Gene Storm)

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