When fat adapts: From physiological remodeling to disease

Adipose tissue undergoes extensive remodeling to adapt to changing physiological demands. This plasticity encompasses changes in adipocyte metabolism and number, extracellular matrix organization, vascularization, immune composition, and innervation. When coordinated, these processes preserve energy buffering, thermogenesis, endocrine function, and local tissue support. Pathological adipose tissue remodeling drives obesity-related complications and contributes to many diseases involving organ-associated adipose depots throughout the body. In cancer, tumor-associated fat can develop a metabolic and fibroinflammatory niche that promotes tumor growth and invasion, and remodeling of other depots can directly disrupt neighboring tissues. Recent studies have identified mesenchymal, immune, vascular, and adipocyte states that govern adaptive or pathological outcomes. These findings broaden therapeutic goals beyond reducing fat mass toward restoring adipogenesis, substrate turnover, thermogenic capacity, and tissue-niche function.