Metabolic dysfunction-associated steatotic liver disease (MASLD) is shaped by metabolic injury and tissue mechanics. This study investigated whether liver stiffening occurs early in MASLD and how extracellular matrix (ECM) mechanics interact with lipid droplet (LD) overload to promote inflammation, fibrogenesis, and lipid dysmetabolism. Clinical data, mouse models, and in vitro experiments are integrated. Liver stiffness shifted modestly with steatosis but increased substantially in the presence...