Delia Y Omar, Mathilda M Willoughby, Nourhan Mostafa, Kelly Otakhor, Saumya Bhatt, Mohammad A Abbas Zaidi, Micah B Schott
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Lipid Droplet Dynamics in Alcoholic Steatohepatitis.
Alcohol-associated liver disease poses a significant global health burden, with alcoholic steatohepatitis (ASH) representing a severe subtype driven by chronic alcohol consumption, hepatic inflammation, and limited treatment options. Central to ASH pathogenesis is the dysregulation of lipid droplet (LD) dynamics in hepatocytes. This review explores the critical role of LDs, focusing on alcohol-induced disruptions in LD biogenesis and catabolism. Chronic ethanol exposure enhances LD biogenesis from lipid import and de novo lipogenesis, while impairing LD catabolism by inhibiting lipolysis and lipophagy. Also, the review article examines alcohol's effect on remodeling the LD proteome and lipidome, including post-translational modifications. Additionally, LDs emerge as morphologic markers in hepatic stellate cells, where their loss drives fibrosis. Recent advances highlight potential therapeutic targets, such as restoring lipophagy or modulating LD biogenesis, offering hope for effective ASH treatments. This review underlines LDs as pivotal organelles in ASH progression and therapeutic innovation.
期刊介绍:
The American Journal of Pathology, official journal of the American Society for Investigative Pathology, published by Elsevier, Inc., seeks high-quality original research reports, reviews, and commentaries related to the molecular and cellular basis of disease. The editors will consider basic, translational, and clinical investigations that directly address mechanisms of pathogenesis or provide a foundation for future mechanistic inquiries. Examples of such foundational investigations include data mining, identification of biomarkers, molecular pathology, and discovery research. Foundational studies that incorporate deep learning and artificial intelligence are also welcome. High priority is given to studies of human disease and relevant experimental models using molecular, cellular, and organismal approaches.