IRS1 and Obesity: Several mechanisms are involved in the etiopathogenesis of obesity-related IR, characterized by changes in several steps of insulin signaling, with reduction in IR concentration and kinase activity, in IRS-1 and IRS-278 phosphorylation into tyrosine, and in PI3K activity.79 In addition, a significant increase in abdominal adipose tissue induces the delivery of free fatty to the liver through the portal vein, aggravating hepatic insulin resistance,80 thereby increasing the release of proinflammatory cytokines through the portal vein, which acts as a feedback to the process.81