The epicardium is not only the source of secreted proteins, but also a multipotent progenitor that undergoes mesenchymal transformation to generate a number of fates. Two fates that are established are fibroblast and smooth muscle cells. We examined adipogenesis as a third candidate fate (Yamaguchi et al, 2015). The hearts of most adult mammals are surrounded by an extensive layer of fat called epicardial adipose tissue, or EAT. This tissue has been speculated to have a number of functions, both beneficial and detrimental, but no experimental exploration of these functions had been possible because the experimentally accessible model species including mice and rats were thought to not have it. Our analysis revealed that EAT does exist in the adult mouse heart, and we demonstrated by fate mapping that it derives from the epicardium. We demonstrated the molecular limitation that keeps mouse epicardium from becoming fat, and the release that allows human epicardium to become fat. We also showed in vivo that we could prevent the formation of mouse EAT, or induce it ectopically, based on these insights. Our current studies are oriented to evaluation of some candidate functions of this tissue using these models.