Semin Liver Dis 2023; 43(04): 367-382
DOI: 10.1055/a-2186-3557
Review Article

Mechanisms of Lipid Droplet Accumulation in Steatotic Liver Diseases

Joseph L. Dempsey
1   Division of Gastroenterology, Department of Medicine, School of Medicine, University of Washington, Seattle, Washington
George N. Ioannou
1   Division of Gastroenterology, Department of Medicine, School of Medicine, University of Washington, Seattle, Washington
2   Division of Gastroenterology, Veterans Affairs Puget Sound Healthcare System Seattle, Washington
Rotonya M. Carr
1   Division of Gastroenterology, Department of Medicine, School of Medicine, University of Washington, Seattle, Washington
› Author Affiliations


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.

Publication History

Accepted Manuscript online:
05 October 2023

Article published online:
06 November 2023

© 2023. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

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