Adipose tissue insulin sensitivity and macrophage recruitment: Does PI3K pick the pathway?

In the United States, obesity is a burgeoning health crisis, with over 30% of adults and nearly 20% of children classified as obese. Insulin resistance, a common metabolic complication associated with obesity, significantly increases the risk of developing metabolic diseases such as hypertension, coronary heart disease, stroke, type 2 diabetes, and certain cancers. With the seminal finding that obese adipose tissue harbors cytokine secreting immune cells, obesity-related research over the past decade has focused on understanding adipocyte–macrophage crosstalk and its impact on systemic insulin sensitivity. Indeed, adipose tissue has emerged as a central mediator of obesity- and diet-induced insulin resistance. In this mini-review, we focus on a potential role of adipose tissue phosphoinositide 3-kinase (PI3K) as a point of convergence of cellular signaling pathways that integrates nutrient sensing and inflammatory signaling to regulate tissue insulin sensitivity.