Adipose Tissue Heterogeneity: Depot-Specific Location and Functional Specialization in Obesity-Related Disease

Adipose tissue is now recognized as a heterogeneous endocrine and metabolic organ rather than a passive lipid reservoir. Beyond the classical white, brown, and beige adipocytes, several depot- and organ-specific lipid-storing cell populations, including pink adipocytes, bone marrow (yellow) adipocytes, and hepatic stellate cells, contribute to energy homeostasis, thermogenesis, immune regulation, bone marrow function, and hepatic retinoid storage. Most existing reviews address these populations separately or focus narrowly on classical depots. Here, we integrate classical and non-classical adipocyte populations within a single depot-specific framework, examining how anatomical location and functional specialization jointly determine their contribution to obesity-related non-communicable diseases, including type 2 diabetes mellitus, metabolic-associated fatty liver disease, hypertension, and atherosclerotic cardiovascular disease. We further highlight unresolved mechanistic questions, including macrophage phenotypic heterogeneity beyond the classical M1/M2 model, the translational limits of brown adipose tissue activation, and the paracrine role of perivascular adipose tissue, that represent priority areas for future investigation.