IRS1 and metabolic disease: In turn, pro-inflammatory cytokine release mediated by immune cells induces serine phosphorylation of insulin receptor substrate-1 (IRS-1) leading to local and systemic insulin resistance, which is thought to contribute toward whole body glucose and fatty acid metabolic dysregulation (24, 25) Furthermore, the obese adipose tissue can exhibit a pro-fibrotic phenotype characterized by an increased expression of ECM proteins such as collagen, which can impact adiposity, glucose homeostasis, and susceptibility to metabolic disease (26–29).