Cutting edge: ferroptosis in metabolic dysfunction-associated steatotic liver disease (MASLD) pathogenesis and therapy

Abstract

Ferroptosis denotes a distinct form of controlled cell death marked by substantial iron buildup and significant lipid peroxidation, playing a crucial role in several disease processes linked to cell death. Given the liver's essential functions in iron and lipid metabolism and its vulnerability to oxidative damage, more research has investigated the correlation between ferroptosis and numerous hepatic diseases, including metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD). NAFLD has arisen as a worldwide public health concern due to elevated morbidity and high death rates. The pathogenesis of MASLD remains incompletely elucidated. Recent data suggests that ferroptosis is crucial in the pathophysiology of MASLD; nevertheless, the specific processes by which ferroptosis influences MASLD remain unclear. The present review summarizes the molecular processes of ferroptosis and its intricate regulatory networks, outlines the differing impacts of ferroptosis at different stages of MASLD, and examines possible approaches targeting ferroptosis for the therapy of MASLD, suggesting a novel approach for its management.

Keywords: Ferroptosis; Iron; Lipid; MASLD; Pathogenesis.