Journal Article

Type I interferon sensing unlocks dormant adipocyte inflammatory potential

Stankiewicz, Traci E., Alarcon, Pablo C., Helmrath, Michael A., Weirauch, Matthew T., Divanovic, Senad, Chan, Calvin C., Mukherjee, Rajib, Chen, Xiaoting, Cappelletti, Monica, Oates, Jarren R., Karns, Rebekah, Moreno-Fernandez, Maria E., Damen, Michelle S. M. A., Doll, Jessica R., Inge, Thomas H.

2020

Overview

White adipose tissue inflammation, in part via myeloid cell contribution, is central to obesity pathogenesis. Mechanisms regulating adipocyte inflammatory potential and consequent impact of such inflammation in disease pathogenesis remain poorly defined. We show that activation of the type I interferon (IFN)/IFNα receptor (IFNAR) axis amplifies adipocyte inflammatory vigor and uncovers dormant gene expression patterns resembling inflammatory myeloid cells. IFNβ-sensing promotes adipocyte glycolysis, while glycolysis inhibition impeded IFNβ-driven intra-adipocyte inflammation. Obesity-driven induction of the type I IFN axis and activation of adipocyte IFNAR signaling contributes to obesity-associated pathogenesis in mice. Notably, IFNβ effects are conserved in human adipocytes and detection of the type I IFN/IFNAR axis-associated signatures positively correlates with obesity-driven metabolic derangements in humans. Collectively, our findings reveal a capacity for the type I IFN/IFNAR axis to regulate unifying inflammatory features in both myeloid cells and adipocytes and hint at an underappreciated contribution of adipocyte inflammation in disease pathogenesis. White adipose inflammation can occur in obesity and is at least in part mediated by inflammatory immune cells. Here the authors show that the Type I Interferon/Interferon alpha-beta receptor axis promotes an inflammatory, glycolysis associated adipocyte phenotype.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 13/106 / 13/21 / 13/31 / 38/77 / 38/88 / 45/91 / 631/250/127/1212 / 631/250/256 / 631/443/319/1642/393 / 64/60 / Activation / Adipocytes / Adipocytes - metabolism / Adipose tissue / Animals / Disease Models, Animal / Gene Expression / Glycolysis / Humanities and Social Sciences / Humans / Immune system / Inflammation / Inflammation - metabolism / Interferon / Interferon Type I - metabolism / Interferon-beta - metabolism / Male / Mice / Mice, Inbred C57BL / multidisciplinary / Myeloid cells / Myeloid Cells - metabolism / Obesity / Obesity - metabolism / Pathogenesis / Phenotypes / Receptor, Interferon alpha-beta - metabolism / Receptors / Science / Science (multidisciplinary) / Vigor / α-Interferon / β-Interferon