PPARγ neddylation essential for adipogenesis is a potential target for treating obesity

H. S. Park, U. I. Ju, J. W. Park, J. Y. Song, D. H. Shin, K. H. Lee, L. S. Jeong, J. Yu, H. W. Lee, J. Y. Cho, S. Y. Kim, S. W. Kim, J. B. Kim, K. S. Park, Y. S. Chun

Research output: Contribution to journalArticlepeer-review

61 Scopus citations


The preadipocyte-to-adipocyte differentiation (adipogenesis) is a key process in fat mass increase and thus it is regarded as a compelling target for preventing or treating obesity. Of adipogenic hormone receptors, peroxisome proliferator-activated receptor gamma (PPARγ) has crucial roles in adipogenesis and lipid accumulation within adipocytes. Here we demonstrate that the NEDD8 (neuronal precursor cell expressed, developmentally downregulated 8)-based post-translation modification (neddylation) of PPARγ is essential for adipogenesis. During adipogenesis, NEDD8 is robustly induced in preadipocytes and conjugates with PPARγ, leading to PPARγ stabilization. When the neddylation process was blocked by NEDD8-targeting siRNAs (or viral vectors) or an inhibitor MLN4924, adipocyte differentiation and fat tissue development were substantially impaired. We also demonstrate that MLN4924 effectively prevents the high-fat diet-induced obesity and glucose intolerance in mice. This study provides a better understanding of how the PPARγ signaling pathway starts and lasts during adipogenesis and a potential anti-obesity strategy that targets the neddylation of PPARγ.

Original languageEnglish
Pages (from-to)1296-1311
Number of pages16
JournalCell Death and Differentiation
Issue number8
StatePublished - 1 Aug 2016

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© 2016 Macmillan Publishers Limited.


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