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Metabolic Dysfunction-Associated Steatotic Liver Disease: From Basic Science to Therapy
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Metabolic Dysfunction-Associated Steatotic Liver Disease: From Basic Science to Therapy

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: 20 October 2025 | Viewed by 5598

Special Issue Editor

Dr. Łukasz Bułdak

E-Mail Website
Guest Editor
Department of Internal Medicine and Clinical Pharmacology, Faculty of Medical Sciences in Katowice, Medical University of Silesia, Medyków 18, 40-752 Katowice, Poland
Interests: internal medicine; endocrinology; clinical pharmacology; obesity; metabolic diseases; hyperlipidemia; diabetes; arterial hypertension
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Metabolic dysfunction-associated steatotic liver disease (MASLD) has become an important healthcare issue. To reduce the potential associated complications, including liver cirrhosis and hepatocellular carcinoma, a rapid response to this issue is of utmost importance. In order to achieve such a goal, significant research efforts in the field of liver studies are necessary. With this in mind, we hereby invite you to contribute novel papers on the different mechanisms involved in the development of liver steatosis and its progression toward inflammation and carcinogenesis. A great addition to this Special Issue would be manuscripts on therapeutic approaches toward MASLD, both in vitro and in vivo. Finally, we also encourage the submission of papers in clinical settings showing the potential benefits of currently approved drugs that might find usage in MASLD treatment.

Dr. Łukasz Bułdak
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

  • MASLD
  • liver steatosis
  • steatohepatitis
  • liver cirrhosis
  • hepatocellular carcinoma
  • in vivo
  • in vitro
  • therapy

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Published Papers (4 papers)

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Research

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21 pages, 3729 KiB  
Article
Submicron Dispersions of Phytosterols Reverse Liver Steatosis with Higher Efficacy than Phytosterol Esters in a Diet Induced-Fatty Liver Murine Model
by Raimundo Gillet, Tomás G. Cerda-Drago, María C. Brañes and Rodrigo Valenzuela
Int. J. Mol. Sci. 2025, 26(2), 564; https://doi.org/10.3390/ijms26020564 - 10 Jan 2025
Cited by 2 | Viewed by 878
Abstract
Consumption of phytosterols is a nutritional strategy employed to reduce cholesterol absorption, but recent research shows that their biological activity might go beyond cholesterol reduction for the treatment of metabolic dysfunction-associated fatty liver disease (MAFLD), and novel phytosterol formulations, such as submicron dispersions, [...] Read more.
Consumption of phytosterols is a nutritional strategy employed to reduce cholesterol absorption, but recent research shows that their biological activity might go beyond cholesterol reduction for the treatment of metabolic dysfunction-associated fatty liver disease (MAFLD), and novel phytosterol formulations, such as submicron dispersions, could improve these effects. We explored the therapeutic activity of phytosterols, either formulated as submicron dispersions of phytosterols (SDPs) or conventional phytosterol esters (PEs), in a mouse model of MAFLD. MAFLD was induced in mice by atherogenic diet (AD) feeding. The reversion of distorted serum and liver parameter values after a period of AD feeding was investigated after supplementation of the AD with SDPs, PEs, or a placebo (PT). Additionally, the metabolic parameters of fatty acid synthesis, fatty acid oxidation, and inflammation were studied to understand the mechanism of action of phytosterols. AD supplementation with SDPs was shown to reduce liver fat, along with showing a significant improvement in liver triglycerides (TGs), free fatty acids (FFAs), and liver cholesterol levels. These results were reinforced by the analyses of the liver steatosis scores, and liver histologies, where SDP intervention showed a consistent improvement. Treatment with PEs showed slighter effects in the same analyses, and no effects were observed with the PT treatment. Additionally, SDP intervention reversed, with a higher efficacy than PEs, the effect of AD on the serum levels of TGs, total- and LDL-cholesterol levels, and glucose levels. And, exceptionally, while SDP improved HDL-cholesterol serum levels, PEs did not show any effect on this parameter. We provide evidence for the therapeutical activity of phytosterols in MAFLD beyond the regulation of cholesterol levels, which is increased when the phytosterols are formulated as submicron dispersions compared to ester formulations. Full article
(This article belongs to the Special Issue Metabolic Dysfunction-Associated Steatotic Liver Disease: From Basic Science to Therapy)
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Review

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47 pages, 1198 KiB  
Review
Hidden in the Fat: Unpacking the Metabolic Tango Between Metabolic Dysfunction-Associated Steatotic Liver Disease and Metabolic Syndrome
by Mariana Boulos, Rabia S. Mousa, Nizar Jeries, Elias Simaan, Klode Alam, Bulus Bulus and Nimer Assy
Int. J. Mol. Sci. 2025, 26(7), 3448; https://doi.org/10.3390/ijms26073448 - 7 Apr 2025
Viewed by 847
Abstract
Metabolic syndrome (MetS) and metabolic dysfunction-associated steatotic liver disease (MASLD) are closely related, with rapidly increasing prevalence globally, driving significant public health concerns. Both conditions share common pathophysiological mechanisms such as insulin resistance (IR), adipose tissue dysfunction, oxidative stress, and gut microbiota dysbiosis, [...] Read more.
Metabolic syndrome (MetS) and metabolic dysfunction-associated steatotic liver disease (MASLD) are closely related, with rapidly increasing prevalence globally, driving significant public health concerns. Both conditions share common pathophysiological mechanisms such as insulin resistance (IR), adipose tissue dysfunction, oxidative stress, and gut microbiota dysbiosis, which contribute to their co-occurrence and progression. While the clinical implications of this overlap, including increased cardiovascular, renal, and hepatic risk, are well recognized, current diagnostic and therapeutic approaches remain insufficient due to the clinical and individuals’ heterogeneity and complexity of these diseases. This review aims to provide an in-depth exploration of the molecular mechanisms linking MetS and MASLD, identify critical gaps in our understanding, and highlight existing challenges in early detection and treatment. Despite advancements in biomarkers and therapeutic interventions, the need for a comprehensive, integrated approach remains. The review also discusses emerging therapies targeting specific pathways, the potential of precision medicine, and the growing role of artificial intelligence in enhancing research and clinical management. Future research is urgently needed to combine multi-omics data, precision medicine, and novel biomarkers to better understand the complex interactions between MetS and MASLD. Collaborative, multidisciplinary efforts are essential to develop more effective diagnostic tools and therapies to address these diseases on a global scale. Full article
(This article belongs to the Special Issue Metabolic Dysfunction-Associated Steatotic Liver Disease: From Basic Science to Therapy)
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39 pages, 1593 KiB  
Review
The Microbiome and Metabolic Dysfunction-Associated Steatotic Liver Disease
by Diren Beyoğlu and Jeffrey R. Idle
Int. J. Mol. Sci. 2025, 26(7), 2882; https://doi.org/10.3390/ijms26072882 - 22 Mar 2025
Viewed by 948
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a condition wherein excessive fat accumulates in the liver, leading to inflammation and potential liver damage. In this narrative review, we evaluate the tissue microbiota, how they arise and their constituent microbes, and the role of [...] Read more.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a condition wherein excessive fat accumulates in the liver, leading to inflammation and potential liver damage. In this narrative review, we evaluate the tissue microbiota, how they arise and their constituent microbes, and the role of the intestinal and hepatic microbiota in MASLD. The history of bacteriophages (phages) and their occurrence in the microbiota, their part in the potential causation of MASLD, and conversely, “phage therapy” for antibiotic resistance, obesity, and MASLD, are all described. The microbiota metabolism of bile acids and dietary tryptophan and histidine is defined, together with the impacts of their individual metabolites on MASLD pathogenesis. Both periodontitis and intestinal microbiota dysbiosis may cause MASLD, and how individual microorganisms and their metabolites are involved in these processes is discussed. Novel treatment opportunities for MASLD involving the microbiota exist and include fecal microbiota transplantation, probiotics, prebiotics, synbiotics, tryptophan dietary supplements, intermittent fasting, and phages or their holins and endolysins. Although FDA is yet to approve phage therapy in clinical use, there are multiple FDA-approved clinical trials, and this may represent a new horizon for the future treatment of MASLD. Full article
(This article belongs to the Special Issue Metabolic Dysfunction-Associated Steatotic Liver Disease: From Basic Science to Therapy)
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31 pages, 1225 KiB  
Review
Metabolomic Hallmarks of Obesity and Metabolic Dysfunction-Associated Steatotic Liver Disease
by Diren Beyoğlu, Yury V. Popov and Jeffrey R. Idle
Int. J. Mol. Sci. 2024, 25(23), 12809; https://doi.org/10.3390/ijms252312809 - 28 Nov 2024
Cited by 6 | Viewed by 2498
Abstract
From a detailed review of 90 experimental and clinical metabolomic investigations of obesity and metabolic dysfunction-associated steatotic liver disease (MASLD), we have developed metabolomic hallmarks for both obesity and MASLD. Obesity studies were conducted in mice, rats, and humans, with consensus biomarker groups [...] Read more.
From a detailed review of 90 experimental and clinical metabolomic investigations of obesity and metabolic dysfunction-associated steatotic liver disease (MASLD), we have developed metabolomic hallmarks for both obesity and MASLD. Obesity studies were conducted in mice, rats, and humans, with consensus biomarker groups in plasma/serum being essential and nonessential amino acids, energy metabolites, gut microbiota metabolites, acylcarnitines and lysophosphatidylcholines (LPC), which formed the basis of the six metabolomic hallmarks of obesity. Additionally, mice and rats shared elevated cholesterol, humans and rats shared elevated fatty acids, and humans and mice shared elevated VLDL/LDL, bile acids and phosphatidylcholines (PC). MASLD metabolomic studies had been performed in mice, rats, hamsters, cows, geese, blunt snout breams, zebrafish, and humans, with the biomarker groups in agreement between experimental and clinical investigations being energy metabolites, essential and nonessential amino acids, fatty acids, and bile acids, which lay the foundation of the five metabolomic hallmarks of MASLD. Furthermore, the experimental group had higher LPC/PC and cholesteryl esters, and the clinical group had elevated acylcarnitines, lysophosphatidylethanolamines/phosphatidylethanolamines (LPE/PE), triglycerides/diglycerides, and gut microbiota metabolites. These metabolomic hallmarks aid in the understanding of the metabolic role played by obesity in MASLD development, inform mechanistic studies into underlying disease pathogenesis, and are critical for new metabolite-inspired therapies. Full article
(This article belongs to the Special Issue Metabolic Dysfunction-Associated Steatotic Liver Disease: From Basic Science to Therapy)
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