Advances in Metabolic Disorders: Mechanisms and Therapeutic Strategies for MASLD/MASH

Metabolic dysfunction-associated steatotic liver disease (MASLD) and its progressive form, metabolic dysfunction-associated steatohepatitis (MASH), are significant contributors to the global burden of chronic liver disease. These conditions are closely linked to obesity, insulin resistance, and metabolic syndrome. MASH is characterized by excessive accumulation of lipids in the liver, inflammation, and progressive fibrosis, which may ultimately lead to cirrhosis and hepatocellular carcinoma if left untreated. Despite the rising prevalence of MASLD/MASH, effective treatment options are limited. Recently, resmetirom and semaglutide have been approved by US-FDA for MASH treatment. However, their use may be constrained by potential adverse effects, including hepatotoxicity, gallbladder-related complications, gastrointestinal disturbances, and acute pancreatitis. Therefore, continued advances in molecular biology, biomarker discovery, and therapeutic innovation, including new pharmaceuticals and natural compounds, are essential to improve early diagnosis, optimize disease management, and enhance clinical outcomes in MASLD/MASH.Currently, more than 115 million people worldwide are affected by MASH. A modelling study predicts a 63% increase in MASH cases by 2030. Approximately 20%-30% of MASLD patients may progress to MASH, while individuals with type 2 diabetes have a higher prevalence of MASLD (60%-70%) and MASH (37%). If the damage persists, MASH further progresses to fibrosis, which can advance to severe scarring, i.e. cirrhosis, ultimately resulting in end-stage liver diseases, such as hepatocellular carcinoma (HCC). Despite the slow progression of fibrosis (~14 years/stage), MASH significantly elevates the risk of HCC (0.5–3%). Although recent therapeutic advances, including the approval of agents such as resmetirom and semaglutide, mark significant progress, their clinical utility is limited by safety concerns and variable efficacy. Therefore, this research topic aims to address the urgent need for a deeper understanding of disease mechanisms and to develop safer, more effective therapeutic strategies. The main emphasis of this topic is elucidating molecular pathways, identifying reliable biomarkers for early diagnosis, and exploring innovative treatment approaches, including novel pharmacological agents and evidence-based natural compounds, to improve disease management and patient outcomes.This Research Topic will encompass multidisciplinary research aimed at advancing the understanding and management of MASLD and MASH. The scope includes studies on molecular and cellular mechanisms underlying disease initiation and progression, particularly those related to lipid metabolism, insulin resistance, inflammation, oxidative stress, and fibrosis. It will also cover the identification and validation of diagnostic and prognostic biomarkers, including non-invasive approaches. In addition, the topic invites research on emerging therapeutic strategies, including novel pharmacological agents, drug repurposing, and natural or herbal compounds with proven efficacy. Topic editors: Dr Uma Shanker Navik, Ralf Weiskirchen Source: https://www.frontiersin.org/research-topics/80062/advances-in-metabolic-disorders-mechanisms-and-therapeutic-strategies-for-masldmash