IRS1 and obesity due to melanocortin 4 receptor deficiency: In addition, one study reported that weight loss in obese PCOS patients resulted in increased expression of insulin receptor substrate 1 in the endothelium and increased expression of glucose transporter protein 1, resulting in improved endothelial function (34).Growing pieces of evidence suggest that activated sympathetic nervous system takes part in PCOS and obesity pathogenesis (35).