Animal models of lean metabolic dysfunction-associated steatotic liver disease (MASLD): bridging pathogenesis and novel drug discovery

INTRODUCTION: Lean metabolic dysfunction - associated steatotic liver disease (MASLD) occurs in individuals with normal BMI and is linked to progressive liver injury, fibrosis, hepatocellular carcinoma, and adverse metabolic outcomes. Its distinct clinical and biological features underscore the need for tailored diagnostic and therapeutic strategies. AREAS COVERED: ) reveal roles for autophagy, microbial DNA sensing, and metabolic rewiring. These platforms have been used to test candidate therapies, including GLP-1 analogues (exendin-4, liraglutide), kinsenoside, silibinin, and bile-acid modulators, and to interrogate gut - liver axis disruption that supports microbiota-targeted strategies. EXPERT OPINION: Lean MASLD is mechanistically distinct from obesity-related MASLD. Animal models have advanced our understanding of their unique drivers, including bile acid dysregulation, leptin signaling, and oxidative stress. These insights may guide the development of targeted therapies tailored to lean patients and improve clinical outcomes through individualized approaches.