Adipose tissue insulin sensitivity and macrophage recruitment Does PI 3 K pick the pathway ?

Obesity and its associated metabolic diseases are one of the greatest public health challenges in the United States. Insulin resistance, a central and defining feature of obesity, has been identified as a primary contributor to the increase in many metabolic diseases including type 2 diabetes, cardiovascular disease, and hypertension. Currently, obesity-induced insulin resistance is proposed to arise secondary to an inflammatory response that is caused by an infiltration of adipose tissue by monocytes and subsequent pro-inflammatory macrophage differentiation. Adipose tissue macrophages release pro-inflammatory cytokines that act both locally on adipocytes and vascular cells and also circulate to distal tissues to stimulate intracellular pro-inflammatory pathways. In a feed-forward cycle, these cytokines can also stimulate adipose tissue macrophages to secrete chemokines that promote the recruitment and infiltration of additional monocytes/macrophages into adipose tissue. These combined actions result in cellautonomous insulin resistance in adipocytes, exacerbation of the