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Peroxiredoxin 4 inhibits insulin-induced adipogenesis through regulation of ER stress in 3T3-L1 cells

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Abstract

Obesity was originally considered a disease endemic to developed countries but has since emerged as a global health problem. Obesity is characterized by abnormal or excessive lipid accumulation (World Health Organization, WHO) resulting from pre-adipocyte differentiation (adipogenesis). The endoplasmic reticulum (ER) produces proteins and cholesterol and shuttles these compounds to their target sites. Many studies have implicated ER stress, indicative of ER dysfunction, in adipogenesis. Reactive oxygen species (ROS) are also known to be involved in pre-adipocyte differentiation. Prx4 specific to the ER lumen exhibits ROS scavenging activity, and we thereby focused on ER-specific Prx4 in tracking changes in adipocyte differentiation and lipid accumulation. Overexpression of Prx4 reduced ER stress and suppressed lipid accumulation by regulating adipogenic gene expression during adipogenesis. Our results demonstrate that Prx4 inhibits ER stress, lowers ROS levels, and attenuates pre-adipocyte differentiation. These findings suggested enhancing the activity of Prx4 may be helpful in the treatment of obesity; the data also support the development of new therapeutic approaches to obesity and obesity-related metabolic disorders.

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Acknowledgements

Jae Yeop Kim, Mi Hye Kim and Dong-Seok Lee performed the experiment and wrote the paper. Hong Jun Lee, Jae-Won Huh, Sang-Rae Lee, Hyun-Shik Lee designed the study and experiments.

Funding

This research was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean Government [NRF-2015R1A4A1042271, NRF-2017R1A2B4008176 and MSIT, NRF-2017R1A5A2015391], and the KRIBB Research Initiative Program [KGM4622013].

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  1. Jae Yeop Kim and Mi Hye Kim have contributed equally to this work and are co-first authors.

Authors and Affiliations

  1. School of Life Sciences, BK21 Plus KNU Creative Bioresearch Group, Kyungpook National University, Daegu, Republic of Korea

    Jae Yeop Kim, Mi Hye Kim, Hyun-Shik Lee & Dong-Seok Lee

  2. School of Life Sciences & Biotechnology, College of Natural Sciences, Kyungpook National University, Daegu, Republic of Korea

    Jae Yeop Kim, Mi Hye Kim, Hyun-Shik Lee & Dong-Seok Lee

  3. College of Medicine, Chungbuk National University, Chungbuk, Republic of Korea

    Hong Jun Lee

  4. Research Institute, E-Biogen Inc, Seoul, Korea

    Hong Jun Lee

  5. National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju, Republic of Korea

    Jae-Won Huh & Sang-Rae Lee

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Kim, J.Y., Kim, M.H., Lee, H.J. et al. Peroxiredoxin 4 inhibits insulin-induced adipogenesis through regulation of ER stress in 3T3-L1 cells. Mol Cell Biochem 468, 97–109 (2020). https://doi.org/10.1007/s11010-020-03714-w

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