Metabolically Activated Macrophages in Obesity and Insulin Resistance
Strong evidence supports the idea that macrophage-induced inflammation contributes to insulin resistance in patients with type 2 diabetes. Although adipose tissue macrophages (ATMs) are the main source of inflammatory cytokines in adipose tissue, mechanisms that produce the pro-inflammatory ATM phenotype, and their role in potentiating insulin resistance in humans, remain incompletely understood. Limitations in studying ATMs and delineating their role in disease are due, in part, to the inability of classical models of macrophage inflammation (M1, exposure to bacteria) to accurately represent the complex phenotype of ATMs in vivo. Accordingly, pro-inflammatory ATMs may differ from M1 macrophages with respect to function, mechanisms driving inflammation, and cell surface markers that report inflammation. We have shown that ATMs in obese adipose tissue from humans and mice adopt a unique “metabolically activated” (MMe) phenotype that is distinct from the M1 phenotype. Here, we will discuss the role of MMe macrophages in potentiating inflammation during obesity and insulin resistance, and discuss differences in signaling mechanisms driving inflammation in MMe and M1 macrophages. Our overall goal is to develop therapeutics to selectively inhibit chronic metabolic inflammation to treat insulin resistance while preserving acute inflammation required to protect the host from infections.
Lev Becker is an associate professor in the Ben May Department for Cancer Research at the University of Chicago. His laboratory combines proteomic, bioinformatic, immunologic, and functional approaches to study innate immune cells across a spectrum of diseases and develops therapeutics to target them. He is an inventor/co-inventor of multiple patents, founder of multiple biotech/tech startup companies, recipient of grants from the National Institutes of Health, foundations, venture capital, and pharmaceutical companies, and author/co-author of publications in high-impact journals including Nature, Nature Chemical Biology, Immunity, Cell Metabolism, and Science Translational Medicine.
You can view this virtual lecture one of two ways:
- Via Google Meet
- By phone at 219.390.9347; PIN: 380 435 073#