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Transcriptional activation of PIK3R1 by PPARγ in adipocytes

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Abstract

Phosphatidylinositol 3-kinase (PI3K) plays an important role in the metabolic actions of insulin and is required for adipogenesis. Regulatory subunit 1 of PI3K (PIK3R1) is a critical component of the PI3K signaling pathway. Peroxisome proliferator-activated receptor gamma (PPARγ) is a key regulator of adipogenesis. Although the PPARγ agonist rosiglitazone induces the expression of PIK3R1, the transcriptional regulation of PIK3R1 in adipocytes remains unknown. In this study, we investigated whether PIK3R1 is a direct target of PPARγ. The level of PIK3R1 expression in 3T3-L1 cells was increased after the induction of adipocyte differentiation and was also induced by overexpression of PPARγ. Furthermore, the upregulation of PPARγ-mediated PIK3R1 expression enhanced the insulin-stimulated AKT activation in 3T3-L1 cells. Two putative peroxisome proliferator response elements (PPREs) in the PIK3R1 promoter were identified as PPARγ binding sites. By chromatin immunoprecipitation, we observed that PPARγ interacts with the two PPRE regions of the PIK3R1 promoter in mature adipocytes. In addition, luciferase reporter assays showed that the −1183/−1161 and −573/−551 regions of the PIK3R1 promoter contain essential elements for PPARγ binding. Taken together, these results suggest that PPARγ is essential for the transcriptional activity of PIK3R1 during adipogenesis.

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Acknowledgments

This research was supported by grants from Basic Science Research Program through the National Research Foundation of Korea (NRF) (No. 2012R1A1B3001134), and by the Next-Generation BioGreen 21 Program (No. PJ008116), Rural Development Administration (RDA), Korea.

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Authors and Affiliations

  1. Department of Biology, Research Institute for Basic Science, Kyung Hee University, Seoul, 130-701, Republic of Korea

    Yoon-Jin Kim, Hyun-Ji Kim & Sang Hoon Kim

  2. Hanwoo Experiment Station, National Institute of Animal Science, RDA, Pyeongchang, Republic of Korea

    Ki Yong Chung

  3. School of Biotechnology and Bovine Genome Resources Bank, Yeungnam University, Gyeongsan, Republic of Korea

    Inho Choi

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  1. Yoon-Jin Kim
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  2. Hyun-Ji Kim
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  5. Sang Hoon Kim
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Correspondence to Sang Hoon Kim.

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Kim, YJ., Kim, HJ., Chung, K.Y. et al. Transcriptional activation of PIK3R1 by PPARγ in adipocytes. Mol Biol Rep 41, 5267–5272 (2014). https://doi.org/10.1007/s11033-014-3398-9

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  • DOI: https://doi.org/10.1007/s11033-014-3398-9

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