To investigate the role of adipocyte PU.1 in obesity-related insulin resistance, we generated adipocyte-specific PU.1 knockout (PU.1 AKO) mice by using adiponectin (Adipoq) Cre-mediated excision of PU.1 floxed alleles (Pu1 fl/fl; Adipoq-Cre+/−). This evidence concerns the gene SPI1 and obesity due to melanocortin 4 receptor deficiency.