In the present study, to demonstrate the potential use of a domesticated and rhEPO-producing transgenic pig (Landrace) as a model for DM translational research, we tested EPO responses to hypoxia and the activation of cellular signals such as the PI3K-Akt pathway (Choi et al. 2010; Cokic et al. 2014), and examined whether expressed and circulating rhEPO attenuate HF diet-induced obesity. Here, EPO is linked to obesity due to melanocortin 4 receptor deficiency.