Adipocyte Deficiency Promotes Early Development of Mammary Gland Alveolar Epithelial Cell

ABSTRACT Adipocytes undergo dramatic changes during to support the development of the mammary gland. However, their precise role and mechanism of action in pregnancy and lactation remain poorly understood. To explore how adipocyte elimination influences alveolar epithelial cells (AECs) in the mammary gland, we mated mice expressing the diphtheria toxin receptor ( iDTR ) to those bearing the adiponectin ( adipoq) cre. Using this mouse model of inducible and transient adipocyte ablation, we demonstrated that adipocyte loss promotes early development of AECs. During pregnancy, adipocyte loss induces activation of STAT5 through integrin β1/RAC1, which promotes early differentiation of AECs. During lactation, adipocyte loss results in upregulation of TGFβ/WNT5A expression, thereby triggering early apoptosis of AECs. Collectively, our findings reveal an unanticipated, stage‐specific regulatory function of adipocytes in orchestrating AECs development during pregnancy and lactation.