3T3L1 adipocytes differentiated in the presence of capsaicin acquire a lean adipocyte phenotype with immunosuppressive capabilities. 3T3L1-MBX cells were differentiated into adipocytes in the presence of capsaicin or equivalent volume vehicle control (ethanol) (A) and were analyzed for adiponectin secretion and gene expression (B). The effects of capsaicin differentiation on adiponectin were performed in conjunction with the capsaicin inhibitor capsazepine (C). 3T3L1 cells were treated with 50-µM capsaicin or vehicle control and analyzed for mRNA expression of adipocyte differentiation and browning genes was performed (D). MTCCs were challenged for 24 h with cell-free conditioned media from 3T3L1 cells differentiated with capsaicin, and cytokine secretion was analyzed by ELISA (E). n = 3–8 samples/group. Data were analyzed by 1-way ANOVA and Dunnett’s multiple comparison test (B), 2-way ANOVA and Tukey’s multiple comparison test (C), or unpaired t test (D and E). *P < 0.05, **P < 0.01, ***P < 0.005, ****P < 0.001: significant differences between capsazepine doses of the 50-μM capsaicin treatment. ###P < 0.005, ####P < 0.001: significant differences between capsazepine doses of the 25-μM capsaicin treatment. MTCC, mouse-transformed club cells.