Distinct functions of PPARγ isoforms in regulating adipocyte plasticity

A better understanding of the mechanisms underlying obesity and its comorbidities is key to designing new therapies and treatments. PPAR gamma is a master regulator of adipocyte biology but the functions of its isoforms are poorly distinguished. Here we demonstrated that PPAR gamma 1 is preferentially expressed in catabolic fat depots while PPAR gamma 2 presents itself at a higher level in browning -resistant depots. PPAR gamma 2, but not PPAR gamma 1, responds to endogenous ligands to induce adipogenesis, and the isoforms regulate distinct sets of white and brown adipocyte genes. Moreover, PPAR gamma 1 negatively correlates while PPAR gamma 2 positively correlates with adiposity in human subcutaneous and visceral fat. These results together indicate that PPAR gamma 1 and PPAR gamma 2 have distinct functions in regulating adipocyte plasticity, and future research should take into account the binary roles of both isoforms in order to identify druggable gene targets and pathways relevant for treatment of metabolic disorders. (C) 2016 Elsevier Inc. All rights reserved.