Using a syngeneic estrogen receptor (ER) positive (ER+) breast adenocarcinoma model in DIO mice and microvascular endothelial cells and tumor-associated endothelial cells (TAECs), we established that the LPA/PKD-1-CD36 signaling pathway may regulate microvascular remodeling through modulation of EC differentiation, thus linking obesity to the malignant progression of an ER-positive BC. Here, PKD1 is linked to obesity disorder.