In this study, we investigated the relationship between MafB and obesity using the following two approaches: (1) we reconstituted hematopoietic systems in mice via transplantation of Mafb−/− fetal liver cells and fed these mice a high‐fat diet (HFD), and (2) we fed a HFD to hematopoietic cell‐specific Mafb‐deficient mice (Mafbf/f::Tie‐2‐Cre). The gene discussed is MAFB; the disease is obesity due to melanocortin 4 receptor deficiency.