Mouse models have raised the possibility that PAI-1 is not merely a product of obesity, but has a causal role in obesity and insulin resistance, as PAI-1 inhibition has the potential to reduce obesity and improve insulin sensitivity[39,40], possibly via PAI-1 functioning as an integrator of cell signalling[41]. The gene discussed is SERPINE1; the disease is obesity due to melanocortin 4 receptor deficiency.