Using both PAI-1 knockout mice and WT mice treated with a pharmacological inhibitor of PAI-1 we initially confirmed prior studies implicating a causative role for PAI-1 in obesity and insulin resistance (Ma et al., 2004) and validated our model in relation to whether PAI-1 contributed to the metabolic abnormalities associated with HFD feeding. Here, SERPINE1 is linked to obesity disorder.