Mammary adipocyte plasticity and epithelial crosstalk: roles in development, remodeling, and disease

The mammary gland is a composite organ in which epithelial ducts and alveoli develop within a specialized adipose-rich stroma. Although mammary biology has traditionally been interpreted through an epithelium-centered framework, increasing evidence indicates that mammary adipocytes actively shape mammary development, reproductive remodeling, and disease susceptibility. Across puberty, pregnancy, lactation, and involution, mammary adipocytes undergo dynamic changes in cellular state, morphology, lipid handling, and stromal interactions, reflecting fate-related, phenotypic, and metabolic plasticity. Through adipokines, growth factors, metabolic substrates, extracellular matrix (ECM)-associated mechanical cues, and immune-inflammatory networks, mammary adipocytes influence epithelial behavior and tissue remodeling. Conversely, epithelial expansion, secretory differentiation, and post-weaning regression reshape the adipose-rich stromal niche. Dysregulation of this reciprocal adipose-epithelial ecosystem may contribute to aberrant tissue expansion, local estrogenic or inflammatory amplification, impaired adipose support, and tumor-permissive remodeling. Here, we review stage-specific epithelial-adipocyte crosstalk during mammary development, define mammary adipocyte plasticity across fate-related and functional dimensions, and discuss its relevance to benign breast disorders, tumor-associated remodeling, and disease susceptibility.