Breast cancer (BC) cells exhibit metabolic heterogeneity with different profiles influenced by their microenvironment. Reprogramming supports cancer growth and survival within this complex microenvironment. Our goal was to analyze the metabolic changes in the adipose microenvironment and their impact on BC reprogramming. We used adipose tissue (AT) explants from patients with BC (immediate tumor adjacency -ADJ- and >2 cm distance -DIST-), alongside normal controls (Normal). Additionally, we evaluated the effects of ADJ conditioned media (ADJ-CM) on changes in glucose metabolism in BC cells (MCF7 and T47D). ADJ explants increased MCT1 and decreased Glut4, LDHA and GAPDH protein expression levels compared to Normal explants. A subgroup of patients with high MCT1 also presented increased browning markers. ADJ-CM had a differential effect on MCF7 and T47D lines, decreasing MCT1 protein expression in MCF7 cells but increasing it in T47D cells. In T47D cells, ADJ-CM also downregulated MCT4 expression, while both ADJ-CM and Normal-CM induced an increase (or tendency to increase) in Glut4 transporters. A minority subpopulation with high glucose uptake was identified in T47D cells through cytometry assays. This subpopulation and overall glucose uptake tended to decrease after ADJ-CM treatment. Furthermore, changes in lactate transporter expression were contrasted with lactate efflux assay. 
In sum, metabolic remodeling occurs in both tumor cells and the adipose stroma in BC. Peritumoral adipocytes could be decreasing glucose uptake, glycolysis and intracellular lactate synthesis, contrasting with the potential import of lactate for energy purposes or signaling the browning process. Soluble factors released by the tumor adipose microenvironment could induce a metabolic switch towards lactate utilization, thereby reducing glucose uptake and the glycolytic tumor population.