Mechano-adaptation of adipose tissue: ECM-mediated control of obesity and breast cancer progression

Obesity triggers ample reorganization of adipose tissue through mechanical and biological mechanisms that extend beyond simple energy storage. Here, we analyse how the extracellular matrix (ECM) mechanically controls obesity's effects on tissue function. We examine three interconnected mechanisms: first, how obesity triggers cellular adaptations through hypertrophy, hyperplasia, and phenotypic transitions; second, how these changes activate specific mechanosensitive pathways through ECM-generated forces; and third, how the resulting matrix alterations promote breast cancer progression through coordinated changes in adipocyte phenotype and tissue mechanics. We critically evaluate current in vitro models for studying these processes and discuss their limitations in recapitulating the complex adipose-tumour microenvironment. By elucidating these ECM-mediated mechanisms, we identify potential therapeutic targets for obesity-related pathologies, particularly breast cancer, while noting the broader applicability of these mechanobiological principles to other adipose-associated malignancies.