Rethinking the paradigm: How comparative studies on fatty acid oxidation inform our understanding of T cell metabolism

The classic paradigm of T cell metabolism posits that activated T-eff cells utilize glycolysis to keep pace with increased energetic demands, while resting and T-mem cells rely on the oxidation of fat. In contrast, T-eff cells during graft-versus-host disease (GVHD) increase their reliance on oxidative metabolism and, in particular, on fatty acid oxidation (FAO). To explore the potential mechanisms driving adoption of this alternative metabolism, we first review key pathways regulating FAO across a variety of disparate tissue types, including liver, heart, and skeletal muscle. Based upon these comparative studies, we then outline a consensus network of transcriptional and signaling pathways that predict a model for regulating FAO in T-eff cells during GVHD. This model raises important implications about the dynamic nature of metabolic reprogramming in T cells and suggests exciting future directions for further study of in vivo T cell metabolism. (C) 2015 Elsevier Ltd. All rights reserved.