The steatotic diseases of metabolic dysfunction-associated steatotic liver disease (MASLD), alcohol-associated liver disease (ALD), and chronic hepatitis C (HCV) account for the majority of liver disease prevalence, morbidity, and mortality worldwide. While these diseases have distinct pathogenic and clinical features, dysregulated lipid droplet (LD) organelle biology represents a convergence of pathogenesis in all three. With increasing understanding of hepatocyte LD biology, we now understand the roles of LD proteins involved in these diseases but also how genetics modulate LD biology to either exacerbate or protect against the phenotypes associated with steatotic liver diseases. Here, we review the history of the LD organelle and its biogenesis and catabolism. We also review how this organelle is critical not only for the steatotic phenotype of liver diseases but also for their advanced phenotypes. Finally, we summarize the latest attempts and challenges of leveraging LD biology for therapeutic gain in steatotic diseases. In conclusion, the study of dysregulated LD biology may lead to novel therapeutics for the prevention of disease progression in the highly prevalent steatotic liver diseases of MASLD, ALD, and HCV.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1055/a-2186-3557 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Adipokines regulate the development and progression of MASLD through organellar oxidative stress.
Hepatol Commun
February 2025
Central laboratory, Endocrine and Metabolic Diseases Hospital of Shandong First Medical University, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China.
The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD), which is increasingly being recognized as a leading cause of chronic liver pathology globally, is increasing. The pathophysiological underpinnings of its progression, which is currently under active investigation, involve oxidative stress. Human adipose tissue, an integral endocrine organ, secretes an array of adipokines that are modulated by dietary patterns and lifestyle choices.
View Article and Find Full Text PDFCost-Utility Analysis of Non-Invasive Tests to Initiate Hepatocellular Carcinoma Surveillance in Metabolic Dysfunction-Associated Steatotic Liver Disease.
Am J Gastroenterol
January 2025
Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand.
Background Aims: Non-invasive tests (NITs), e.g. Fibrosis-4 Index (FIB-4) and vibration-controlled elastography (VCTE), have been used to identify metabolic dysfunction-associated steatotic liver disease (MASLD) patients at high risks for hepatocellular carcinoma (HCC).
View Article and Find Full Text PDFPlasma Circulating Metabolites Associated With Steatotic Liver Disease and Liver Enzymes: A Multiplatform Population-Based Study.
Gastro Hep Adv
September 2024
Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Background And Aims: Steatotic liver disease (SLD) is the most common chronic liver disease strongly associated with metabolic dysfunction, but its pathogenesis remains incompletely understood. Exploring plasma circulating metabolites may help in elucidating underlying mechanisms and identifying new biomarkers for SLD.
Methods: We examined cross-sectionally the association between plasma metabolites and SLD as well as liver enzymes using data from 4 population-based cohort studies (Rotterdam study, Avon Longitudinal Study of Parents and Children, The Insulin Resistance Atherosclerosis Family Study, and Study of Latinos).
polysaccharides alleviate metabolic dysfunction-associated steatotic liver disease through enhancing hepatocyte RelA/ HNF1α signaling.
World J Gastroenterol
January 2025
State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Xinjiang Key Laboratory of Molecular Biology for Endemic Diseases, Department of Pathology, School of Basic Medical Sciences, Xinjiang Medical University, Urumqi 830000, Xinjiang Uyghur Autonomous Region, China.
Background: polysaccharides (BSP) have antioxidant, immune regulation, and anti-fibrotic activities. However, the therapeutic effect and mechanisms underlying the action of BSP in metabolic dysfunction-associated steatotic liver disease (MASLD) have not been fully understood.
Aim: To investigate the therapeutic effects and mechanisms of BSP on MASLD by centering on the hepatocyte nuclear factor kappa B p65 (RelA)/hepatocyte nuclear factor-1 alpha (HNF1α) signaling.
Exploring the therapeutic potential of glucagon-like peptide 1 agonists in metabolic disorders.
World J Gastroenterol
January 2025
School of Health Sciences, Universidad Internacional de La Rioja, Logroño 26006, La Rioja, Spain.
This article comments on the work by Soresi and Giannitrapani. The authors have stated that one of the most novel and promising treatments for metabolic dysfunction-associated steatotic liver disease (MASLD) is the use of glucagon-like peptide 1 receptor agonists, especially when used in combination therapy. However, despite their notable efficacy, these drugs were not initially designed to target MASLD directly.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!