To this end, we used a genetic rodent model that lacks ERβ DBD, but retains functions of ERβ that do not require its DNA binding (ERβDBDKO) (Clart et al., 2021), to investigate the role that non-classical signaling of ERβ may play in systemic physiology and adipocyte metabolism in the setting of diet-induced obesity, with an emphasis on its role in mediating WAT browning in response to CL. The gene discussed is ESR2; the disease is Obesity.