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Molecular Targets for the Formation and Treatment of Nonalcoholic Fatty Liver Disease

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (30 August 2023) | Viewed by 9502

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Special Issue Editor

Dr. Evangelos Cholongitas

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Guest Editor

1st Department of Internal Medicine, General Hospital of Athens “Laiko”, Medical School of National and Kapodistrian University of Athens, 11527 Athens, Greece
Interests: non alcoholic liver disease; liver transplantation; cirrhosis; viral hepatitis; liver diseases; hepatitis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Non-alcoholic fatty liver disease (NAFLD) has emerged as the predominant cause of chronic liver injury worldwide, while it is projected to become the leading cause of liver transplantation by 2030. Obesity due to type 2 diabetes and aging is becoming more common and is receiving worldwide attention. NAFLD can progress to non-alcoholic steatohepatitis (NASH), characterized by the presence of liver steatosis and inflammation, with or without fibrosis, and in some fewer cases to liver cirrhosis and hepatocellular carcinoma. Despite the vast scientific effort made globally, until now, no medication for NAFLD has been approved and the current management of patients mostly focuses on lifestyle interventions.

This Special Issue of the International Journal of Molecular Sciences focuses on the recent findings derived from both animal and human studies concerning the pathways involved in the pathogenesis of NAFLD and NAFLD-related hepatocellular carcinoma and the future perspectives for the development of NAFLD-specific treatment.

Dr. Evangelos Cholongitas
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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
hepatocellular carcinoma
pathogenesis
molecular targets
molecular pathways

Published Papers (4 papers)

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Research

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17 pages, 9244 KiB

Open AccessArticle

Pharmacological Prevention of Ectopic Erythrophagocytosis by Cilostazol Mitigates Ferroptosis in NASH

by Joon Beom Park, Kangeun Ko, Yang Hyun Baek, Woo Young Kwon, Sunghwan Suh, Song-Hee Han, Yun Hak Kim, Hye Young Kim and Young Hyun Yoo

Int. J. Mol. Sci. 2023, 24(16), 12862; https://doi.org/10.3390/ijms241612862 - 16 Aug 2023

Cited by 2 | Viewed by 1351

Abstract

Hepatic iron overload (HIO) is a hallmark of nonalcoholic fatty liver disease (NAFLD) with a poor prognosis. Recently, the role of hepatic erythrophagocytosis in NAFLD is emerging as a cause of HIO. We undertook various assays using human NAFLD patient pathology samples and an in vivo nonalcoholic steatohepatitis (NASH) mouse model named STAM^TM. To make the in vitro conditions comparable to those of the in vivo NASH model, red blood cells (RBCs) and platelets were suspended and subjected to metabolic and inflammatory stresses. An insert-coculture system, in which activated THP-1 cells and RBCs are separated from HepG2 cells by a porous membrane, was also employed. Through various analyses in this study, the effect of cilostazol was examined. The NAFLD activity score, including steatosis, ballooning degeneration, inflammation, and fibrosis, was increased in STAM^TM mice. Importantly, hemolysis occurred in the serum of STAM^TM mice. Although cilostazol did not improve lipid or glucose profiles, it ameliorated hepatic steatosis and inflammation in STAM^TM mice. Platelets (PLTs) played an important role in increasing erythrophagocytosis in the NASH liver. Upregulated erythrophagocytosis drives cells into ferroptosis, resulting in liver cell death. Cilostazol inhibited the augmentation of PLT and RBC accumulation. Cilostazol prevented the PLT-induced increase in ectopic erythrophagocytosis in in vivo and in vitro NASH models. Cilostazol attenuated ferroptosis of hepatocytes and phagocytosis of RBCs by THP-1 cells. Augmentation of hepatic erythrophagocytosis by activated platelets in NASH exacerbates HIO. Cilostazol prevents ectopic erythrophagocytosis, mitigating HIO-mediated ferroptosis in NASH models. Full article

(This article belongs to the Special Issue Molecular Targets for the Formation and Treatment of Nonalcoholic Fatty Liver Disease)

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Review

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28 pages, 1138 KiB

Open AccessReview

Glucagon-like Peptide 1, Glucose-Dependent Insulinotropic Polypeptide, and Glucagon Receptor Agonists in Metabolic Dysfunction-Associated Steatotic Liver Disease: Novel Medication in New Liver Disease Nomenclature

by Lampros G. Chrysavgis, Spyridon Kazanas, Konstantina Bafa, Sophia Rozani, Maria-Evangelia Koloutsou and Evangelos Cholongitas

Int. J. Mol. Sci. 2024, 25(7), 3832; https://doi.org/10.3390/ijms25073832 - 29 Mar 2024

Viewed by 2065

Abstract

Glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are incretins that regulate postprandial glucose regulation, stimulating insulin secretion from pancreatic β-cells in response to food ingestion. Modified GLP-1 receptor agonists (GLP-1RAs) are being administered for the treatment of obesity and type 2 diabetes mellitus (T2DM). Strongly related to those disorders, metabolic dysfunction-associated steatotic liver disease (MASLD), especially its aggressive form, defined as metabolic dysfunction-associated steatohepatitis (MASH), is a major healthcare burden associated with high morbidity and extrahepatic complications. GLP-1RAs have been explored in MASH patients with evident improvement in liver dysfunction enzymes, glycemic control, and weight loss. Importantly, the combination of GLP-1RAs with GIP and/or glucagon RAs may be even more effective via synergistic mechanisms in amelioration of metabolic, biochemical, and histological parameters of MASLD but also has a beneficial impact on MASLD-related complications. In this current review, we aim to provide an overview of incretins’ physiology, action, and signaling. Furthermore, we provide insight into the key pathophysiological mechanisms through which they impact MASLD aspects, as well as we analyze clinical data from human interventional studies. Finally, we discuss the current challenges and future perspectives pertinent to this growing area of research and clinical medicine. Full article

(This article belongs to the Special Issue Molecular Targets for the Formation and Treatment of Nonalcoholic Fatty Liver Disease)

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19 pages, 984 KiB

Open AccessReview

Faecal Microbiota Transplantation, Paving the Way to Treat Non-Alcoholic Fatty Liver Disease

by María Del Barrio, Lucía Lavín, Álvaro Santos-Laso, Maria Teresa Arias-Loste, Aitor Odriozola, Juan Carlos Rodriguez-Duque, Coral Rivas, Paula Iruzubieta and Javier Crespo

Int. J. Mol. Sci. 2023, 24(7), 6123; https://doi.org/10.3390/ijms24076123 - 24 Mar 2023

Cited by 8 | Viewed by 2627

Abstract

Non-alcoholic fatty liver disease (NAFLD) is currently the most prevalent cause of chronic liver disease (CLD). Currently, the only therapeutic recommendation available is a lifestyle change. However, adherence to this approach is often difficult to guarantee. Alteration of the microbiota and an increase in intestinal permeability seem to be key in the development and progression of NAFLD. Therefore, the manipulation of microbiota seems to provide a promising therapeutic strategy. One way to do so is through faecal microbiota transplantation (FMT). Here, we summarize the key aspects of FMT, detail its current indications and highlight the most recent advances in NAFLD. Full article

(This article belongs to the Special Issue Molecular Targets for the Formation and Treatment of Nonalcoholic Fatty Liver Disease)

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16 pages, 606 KiB

Open AccessReview

Microsomal Prostaglandin E Synthase-1 and -2: Emerging Targets in Non-Alcoholic Fatty Liver Disease

by Dimitrios Kotsos and Konstantinos Tziomalos

Int. J. Mol. Sci. 2023, 24(3), 3049; https://doi.org/10.3390/ijms24033049 - 3 Feb 2023

Cited by 2 | Viewed by 2723

Abstract

Nonalcoholic fatty liver disease (NAFLD) affects a substantial proportion of the general population and is even more prevalent in obese and diabetic patients. NAFLD, and particularly the more advanced manifestation of the disease, nonalcoholic steatohepatitis (NASH), increases the risk for both liver-related and cardiovascular morbidity. The pathogenesis of NAFLD is complex and multifactorial, with many molecular pathways implicated. Emerging data suggest that microsomal prostaglandin E synthase-1 and -2 might participate in the development and progression of NAFLD. It also appears that targeting these enzymes might represent a novel therapeutic approach for NAFLD. In the present review, we discuss the association between microsomal prostaglandin E synthase-1 and -2 and NAFLD. Full article

(This article belongs to the Special Issue Molecular Targets for the Formation and Treatment of Nonalcoholic Fatty Liver Disease)

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