Obesity leads to various triggering events, such as ER stress, hypoxia, and lipotoxicity, which can initiate activation of proinflammatory pathways within tissue parenchymal cells (Step 1). As part of the activation mechanism in these parenchymal cells, they secrete a variety of chemokines (Step 2), which lead to chemotaxis and migration of macrophages, as well as other immune cell types, into the underlying tissue (Step 3). Overall, these immune cells take on a proinflammatory phenotype and secrete a number of factors (cytokines, galectin-3, miRNA-containing exosomes, etc.), which exert local paracrine effects to cause insulin resistance in adipocytes, hepatocytes, and myocytes, or decreased GSIS in β cells (Step 4).