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Molecular Mechanisms Underlying Fatty Liver Disease: From Pathogenesis to Treatment

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A special issue of Current Issues in Molecular Biology (ISSN 1467-3045). This special issue belongs to the section "Molecular Medicine".

Deadline for manuscript submissions: 31 October 2024 | Viewed by 6281

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Special Issue Editor

Dr. Haibo Dong

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Guest Editor

Center for Translational Biomedical Research, University of North Carolina at Greensboro, North Carolina Research Campus, Kannapolis, NC 28081, USA
Interests: fatty liver diseases; cellular redox balance; cell death; inflammation; oxidative stress; autophagy; mitochondrial dysfunction; NAD⁺ homeostasis

Special Issue Information

Dear Colleagues,

We are pleased to announce the call for papers for a Special Issue in Current Issues in Molecular Biology focused on exploring the cellular and molecular mechanisms that are involved in the development and progression of both non-alcoholic fatty liver disease (NAFLD) and alcohol-associated liver disease (ALD).

NAFLD and ALD are significant contributors to the global burden of liver disease. NAFLD, often associated with metabolic syndrome, obesity, diabetes, and cardiovascular disease, has emerged as the most common cause of chronic liver disease worldwide. ALD, on the other hand, is primarily caused by excessive alcohol consumption and encompasses a wide range of liver conditions, including steatosis, alcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma. NAFLD and ALD are both steatohepatitic processes and share several common features, yet they are different in many aspects. Therefore, understanding the development and progression of both NAFLD and ALD, in addition to uncovering the underlying cellular and molecular mechanisms, is crucial to advancing our knowledge and developing effective therapeutic strategies for treating these liver diseases.

In this Special Issue, we welcome articles that investigate or summarize the cellular and molecular mechanisms that contribute to the pathogenesis and progression of NAFLD, NASH, ALD, and related diseases. We encourage researchers to explore a broad range of topics, including, but not limited to, impaired lipid metabolism, inflammation, oxidative stress, insulin resistance, genetic/epigenetic modifications, and the interplay between alcohol metabolism and liver injury.

Dr. Haibo Dong
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. Current Issues in Molecular Biology is an international peer-reviewed open access monthly 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 2200 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 (NAFLD)
alcohol-associated liver disease (ALD)
lipotoxicity
bile acid metabolism
novel biomarker identification
organelle dysfunction and communication
inflammation and oxidative stress
cell signaling and cell death pathways
lipid metabolism and dysregulation
epigenetic modifications (DNA/RNA/non-coding RNA)
therapeutic targets and interventions

Published Papers (5 papers)

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Research

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12 pages, 1798 KiB

Open AccessArticle

Dimethyloxalylglycine Suppresses SREBP1c and Lipogenic Gene Expressions in Hepatocytes Independently of HIF1A

by Yong Seong Kwon, Ye Eun Cho, Yeonsoo Kim, Minseob Koh and Seonghwan Hwang

Curr. Issues Mol. Biol. 2024, 46(3), 2386-2397; https://doi.org/10.3390/cimb46030151 - 13 Mar 2024

Viewed by 698

Abstract

Dimethyloxalylglycine (DMOG) is a representative inhibitor of the prolyl hydroxylase domain (PHD), which mediates the degradation of hypoxia-inducible factor-1-alpha (HIF1A). DMOG exerts its pharmacological effects via the canonical pathway that involves PHD inhibition; however, it remains unclear whether DMOG affects lipogenic gene expression in hepatocytes. We aimed to elucidate the effects of DMOG on sterol regulatory element-binding protein-1c (SREBP1c), a master regulator of fatty acid synthesis in hepatocytes. DMOG treatment inhibited SREBP1c mRNA and protein expression in HepG2 and AML12 hepatocytes and reduced the transcript levels of SREBP1c-regulated lipogenic genes. A luciferase reporter assay revealed that DMOG inhibited the transcriptional activity of SREBP1c. Moreover, DMOG suppressed SREBP1c expression in mice liver. Mechanistically, treatment with DMOG enhanced the expression of HIF1A and insulin-induced gene 2 (INSIG2), which inhibits the activation of SREBP1c. However, HIF1A or INSIG2 knockdown failed to reverse the inhibitory effect of DMOG on SREBP1c expression, suggesting a redundant role of HIF1A and INSIG2 in terms of repressing SREBP1c. DMOG did not function through the canonical pathway involving inhibition of SREBP1c by PHD, highlighting the presence of non-canonical pathways that mediate its anti-lipogenic effect. Full article

(This article belongs to the Special Issue Molecular Mechanisms Underlying Fatty Liver Disease: From Pathogenesis to Treatment)

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13 pages, 4044 KiB

Open AccessArticle

Assessment of the (Pro)renin Receptor Protein Expression in Organs

by Teng-Yao Yang, Pey-Jium Chang, Yu-Shien Ko, Siou-Ru Shen and Shun-Fu Chang

Curr. Issues Mol. Biol. 2024, 46(3), 1741-1753; https://doi.org/10.3390/cimb46030113 - 25 Feb 2024

Viewed by 689

Abstract

The (pro)renin receptor ((P)RR) is an essential component of the renin–angiotensin system (RAS) as a specific single-pass transmembrane receptor for prorenin and renin and has now emerged as a multifunctional protein implicated in a wide variety of developmental and physio-pathological processes and pathways. The (P)RR may be of pathological significance in metabolic syndrome. The (P)RR has received much consideration; substantial efforts have been made to understand the localization, regulation, and function of the (P)RR at both a molecular and system level. (P)RR regulation of cell function depends on whether it is intact or cleaved into its constituent forms. Therefore, the present chapter describes immunohistochemical approaches to examine the expression of (P)RR in various organs. It was shown that different molecular forms of (P)RR could be present in different tissue compartments in almost all organs. Among them, the liver has high PRR activity. Our findings could elucidate more detailed distribution of different (P)RR molecular forms in different organs, which could provide useful information to further investigate the pathophysiological mechanisms of the development of various diseases in the future. Full article

(This article belongs to the Special Issue Molecular Mechanisms Underlying Fatty Liver Disease: From Pathogenesis to Treatment)

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Review

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18 pages, 676 KiB

Open AccessReview

Gut–Liver Axis as a Therapeutic Target for Drug-Induced Liver Injury

by Wenjing Tao, Qiwen Fan and Jintao Wei

Curr. Issues Mol. Biol. 2024, 46(2), 1219-1236; https://doi.org/10.3390/cimb46020078 - 1 Feb 2024

Viewed by 1259

Abstract

Drug-induced liver injury (DILI) is a liver disease that remains difficult to predict and diagnose, and the underlying mechanisms are yet to be fully clarified. The gut–liver axis refers to the reciprocal interactions between the gut and the liver, and its homeostasis plays a prominent role in maintaining liver health. It has been recently reported that patients and animals with DILI have a disrupted gut–liver axis, involving altered gut microbiota composition, increased intestinal permeability and lipopolysaccharide translocation, decreased short-chain fatty acids production, and impaired bile acid metabolism homeostasis. The present review will summarize the evidence from both clinical and preclinical studies about the role of the gut–liver axis in the pathogenesis of DILI. Moreover, we will focus attention on the potential therapeutic strategies for DILI based on improving gut–liver axis function, including herbs and phytochemicals, probiotics, fecal microbial transplantation, postbiotics, bile acids, and Farnesoid X receptor agonists. Full article

(This article belongs to the Special Issue Molecular Mechanisms Underlying Fatty Liver Disease: From Pathogenesis to Treatment)

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17 pages, 9333 KiB

Open AccessReview

Recent Advances in Liver Tissue Engineering as an Alternative and Complementary Approach for Liver Transplantation

by Dileep G. Nair and Ralf Weiskirchen

Curr. Issues Mol. Biol. 2024, 46(1), 262-278; https://doi.org/10.3390/cimb46010018 - 29 Dec 2023

Cited by 1 | Viewed by 1491

Abstract

Acute and chronic liver diseases cause significant morbidity and mortality worldwide, affecting millions of people. Liver transplantation is the primary intervention method, replacing a non-functional liver with a functional one. However, the field of liver transplantation faces challenges such as donor shortage, postoperative complications, immune rejection, and ethical problems. Consequently, there is an urgent need for alternative therapies that can complement traditional transplantation or serve as an alternative method. In this review, we explore the potential of liver tissue engineering as a supplementary approach to liver transplantation, offering benefits to patients with severe liver dysfunctions. Full article

(This article belongs to the Special Issue Molecular Mechanisms Underlying Fatty Liver Disease: From Pathogenesis to Treatment)

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19 pages, 1523 KiB

Open AccessReview

The Interconnection between Hepatic Insulin Resistance and Metabolic Dysfunction-Associated Steatotic Liver Disease—The Transition from an Adipocentric to Liver-Centric Approach

by Milena Vesković, Nikola Šutulović, Dragan Hrnčić, Olivera Stanojlović, Djuro Macut and Dušan Mladenović

Curr. Issues Mol. Biol. 2023, 45(11), 9084-9102; https://doi.org/10.3390/cimb45110570 - 14 Nov 2023

Cited by 3 | Viewed by 1551

Abstract

The central mechanism involved in the pathogenesis of MAFLD is insulin resistance with hyperinsulinemia, which stimulates triglyceride synthesis and accumulation in the liver. On the other side, triglyceride and free fatty acid accumulation in hepatocytes promotes insulin resistance via oxidative stress, endoplasmic reticulum stress, lipotoxicity, and the increased secretion of hepatokines. Cytokines and adipokines cause insulin resistance, thus promoting lipolysis in adipose tissue and ectopic fat deposition in the muscles and liver. Free fatty acids along with cytokines and adipokines contribute to insulin resistance in the liver via the activation of numerous signaling pathways. The secretion of hepatokines, hormone-like proteins, primarily by hepatocytes is disturbed and impairs signaling pathways, causing metabolic dysregulation in the liver. ER stress and unfolded protein response play significant roles in insulin resistance aggravation through the activation of apoptosis, inflammatory response, and insulin signaling impairment mediated via IRE1/PERK/ATF6 signaling pathways and the upregulation of SREBP 1c. Circadian rhythm derangement and biological clock desynchronization are related to metabolic disorders, insulin resistance, and NAFLD, suggesting clock genes as a potential target for new therapeutic strategies. This review aims to summarize the mechanisms of hepatic insulin resistance involved in NAFLD development and progression. Full article

(This article belongs to the Special Issue Molecular Mechanisms Underlying Fatty Liver Disease: From Pathogenesis to Treatment)

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