Physiological Convergence and Antagonism Between GR and PPAR gamma in Inflammation and Metabolism

Nuclear receptors (NRs) are transcription factors that modulate gene expression in a ligand-dependent manner. The ubiquitously expressed glucocorticoid receptor (GR) and peroxisome proliferator-activated receptor gamma (PPAR gamma) represent steroid (type I) and non-steroid (type II) classes of NRs, respectively. The diverse transcriptional and physiological outcomes of their activation are highly tissue-specific. For example, in subsets of immune cells, such as macrophages, the signaling of GR and PPAR gamma converges to elicit an anti-inflammatory phenotype; in contrast, in the adipose tissue, their signaling can lead to reciprocal metabolic outcomes. This review explores the cooperative and divergent outcomes of GR and PPAR gamma functions in different cell types and tissues, including immune cells, adipose tissue and the liver. Understanding the coordinated control of these NR pathways should advance studies in the field and potentially pave the way for developing new therapeutic approaches to exploit the GR:PPAR gamma crosstalk.