Pin1 enhances adipocyte differentiation by positively regulating the transcriptional activity of PPAR gamma

Abstract

Pin1 is a peptidylprolyl cis/trans isomerase and it has a unique enzymatic activity of catalyzing isomerization of the peptide bond between phospho-serine/threonine and proline. Through the conformational change of its substrates, Pin1 regulates diverse biological processes including adipogenesis. In mouse embryonic fibroblasts and 3T3-L1 preadipocytes, overexpression of Pin1 enhances adipocyte differentiation whereas inhibition of Pin1 activity suppresses it. However, the precise functions of Pin1 during adipogenesis are not clear. In the present study, we investigated the potential targets of Pin1 during adipogenesis. We found that Pin1 interacts directly with and regulates the transcriptional activity of PPAR gamma, a key regulator of adipogenesis. In addition, ERK activity and Ser273 of PPAR gamma, a potential ERK phosphorylation target site, are important for the regulation of PPAR gamma function by Pin1 in 3T3-L1 cells. Taken together our results suggest a novel regulatory mechanism of Pin1 during adipogenesis, in which Pin1 enhances adipocyte differentiation by regulating the function of PPAR gamma. (C) 2016 Elsevier Ireland Ltd. All rights reserved.