Lipotoxicity-driven metabolic dysfunction-associated steatotic liver disease (MASLD) - PubMed (original) (raw)

Review

doi: 10.1016/j.atherosclerosis.2024.119053. Epub 2024 Nov 14.

Claudia Maccali 2, Marco Arrese 3, Patricia Aspichueta [ 4](#full-view-affiliation-4 "Department of Physiology, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), 48940, Leioa, Spain; Biobizkaia Health Research Institute, Cruces University Hospital, 48903, Barakaldo, Spain; National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd, "Instituto de Salud Carlos III"), Spain."), Claudia P Oliveira 5, Rui E Castro 6, Ainhoa Lapitz [ 7](#full-view-affiliation-7 "Department of Liver and Gastrointestinal Diseases, Biogipuzkoa Health Research Institute, Donostia University Hospital, University of the Basque Country (UPV/EHU), Donostia-San Sebastian, Spain; National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd, "Instituto de Salud Carlos III"), Spain."), Laura Izquierdo-Sanchez [ 7](#full-view-affiliation-7 "Department of Liver and Gastrointestinal Diseases, Biogipuzkoa Health Research Institute, Donostia University Hospital, University of the Basque Country (UPV/EHU), Donostia-San Sebastian, Spain; National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd, "Instituto de Salud Carlos III"), Spain."), Luis Bujanda [ 7](#full-view-affiliation-7 "Department of Liver and Gastrointestinal Diseases, Biogipuzkoa Health Research Institute, Donostia University Hospital, University of the Basque Country (UPV/EHU), Donostia-San Sebastian, Spain; National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd, "Instituto de Salud Carlos III"), Spain."), Maria J Perugorria [ 8](#full-view-affiliation-8 "Department of Liver and Gastrointestinal Diseases, Biogipuzkoa Health Research Institute, Donostia University Hospital, University of the Basque Country (UPV/EHU), Donostia-San Sebastian, Spain; National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd, "Instituto de Salud Carlos III"), Spain; Department of Medicine, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), 48940, Leioa, Spain."), Jesus M Banales [ 9](#full-view-affiliation-9 "Department of Liver and Gastrointestinal Diseases, Biogipuzkoa Health Research Institute, Donostia University Hospital, University of the Basque Country (UPV/EHU), Donostia-San Sebastian, Spain; National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd, "Instituto de Salud Carlos III"), Spain; IKERBASQUE, Basque Foundation for Science, Bilbao, Spain; Department of Biochemistry and Genetics, School of Sciences, University of Navarra, Pamplona, Spain. Electronic address: jesusmaria.banalesasurmendi@bio-gipuzkoa.eus."), Pedro M Rodrigues [ 10](#full-view-affiliation-10 "Department of Liver and Gastrointestinal Diseases, Biogipuzkoa Health Research Institute, Donostia University Hospital, University of the Basque Country (UPV/EHU), Donostia-San Sebastian, Spain; National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd, "Instituto de Salud Carlos III"), Spain; IKERBASQUE, Basque Foundation for Science, Bilbao, Spain. Electronic address: pedromiguel.rodriguesvieira@bio-gipuzkoa.eus.")

Affiliations

Free article

Review

Lipotoxicity-driven metabolic dysfunction-associated steatotic liver disease (MASLD)

Santiago Iturbe-Rey et al. Atherosclerosis. 2025 Jan.

Free article

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) encompasses a spectrum of liver lesions, ranging from simple steatosis to metabolic dysfunction-associated steatohepatitis (MASH), that may further progress to cirrhosis. MASLD is estimated to affect more than one third of the general population and it represents a risk factor for end-stage liver failure and liver cancer, substantially contributing to liver-related morbidity and mortality. Although the pathogenesis of MASLD is incompletely understood, it is known to consist of a multifactorial process influenced by extrinsic and intrinsic factors such as metabolic, environmental and demographic features, gut microbiota and genetics. Dysregulation of both extracellular and intracellular lipid composition is known to promote the generation of toxic lipid species, thereby triggering lipotoxicity and cellular stress. These events ultimately lead to the activation of distinct cell death pathways, resulting in inflammation, fibrogenesis and, eventually, carcinogenesis. In this manuscript, we provide a comprehensive review of the role of lipotoxicity during MASLD pathogenesis, discussing the most relevant lipid species and related molecular mechanisms, summarizing the cell type-specific effects and highlighting the most promising putative therapeutic strategies for modulating lipotoxicity and lipid metabolism in MASLD.

Keywords: Cell death; Fatty acids; Lipids; Lipotoxicity; Liver cancer; MASH; MASLD.

Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.

PubMed Disclaimer

Conflict of interest statement

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Publication types

MeSH terms

LinkOut - more resources