IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-33842-4.html
   My bibliography  Save this article

Phosphatase protector alpha4 (α4) is involved in adipocyte maintenance and mitochondrial homeostasis through regulation of insulin signaling

Author

Listed:
  • Masaji Sakaguchi

    (Kumamoto University)

  • Shota Okagawa

    (Kumamoto University)

  • Yuma Okubo

    (Kumamoto University)

  • Yuri Otsuka

    (Kumamoto University)

  • Kazuki Fukuda

    (Kumamoto University
    Kumamoto University)

  • Motoyuki Igata

    (Kumamoto University)

  • Tatsuya Kondo

    (Kumamoto University)

  • Yoshifumi Sato

    (Kumamoto University)

  • Tatsuya Yoshizawa

    (Kumamoto University)

  • Takaichi Fukuda

    (Kumamoto University)

  • Kazuya Yamagata

    (Kumamoto University
    Kumamoto University)

  • Weikang Cai

    (New York Institute of Technology College of Osteopathic Medicine)

  • Yu-Hua Tseng

    (Harvard Medical School)

  • Nobuo Sakaguchi

    (Kumamoto University
    Tokyo Metropolitan Institute of Medical Science)

  • C. Ronald Kahn

    (Harvard Medical School)

  • Eiichi Araki

    (Kumamoto University
    Kumamoto University)

Abstract

Insulin signaling is mediated via a network of protein phosphorylation. Dysregulation of this network is central to obesity, type 2 diabetes and metabolic syndrome. Here we investigate the role of phosphatase binding protein Alpha4 (α4) that is essential for the serine/threonine protein phosphatase 2A (PP2A) in insulin action/resistance in adipocytes. Unexpectedly, adipocyte-specific inactivation of α4 impairs insulin-induced Akt-mediated serine/threonine phosphorylation despite a decrease in the protein phosphatase 2A (PP2A) levels. Interestingly, loss of α4 also reduces insulin-induced insulin receptor tyrosine phosphorylation. This occurs through decreased association of α4 with Y-box protein 1, resulting in the enhancement of the tyrosine phosphatase protein tyrosine phosphatase 1B (PTP1B) expression. Moreover, adipocyte-specific knockout of α4 in male mice results in impaired adipogenesis and altered mitochondrial oxidation leading to increased inflammation, systemic insulin resistance, hepatosteatosis, islet hyperplasia, and impaired thermogenesis. Thus, the α4 /Y-box protein 1(YBX1)-mediated pathway of insulin receptor signaling is involved in maintaining insulin sensitivity, normal adipose tissue homeostasis and systemic metabolism.

Suggested Citation

  • Masaji Sakaguchi & Shota Okagawa & Yuma Okubo & Yuri Otsuka & Kazuki Fukuda & Motoyuki Igata & Tatsuya Kondo & Yoshifumi Sato & Tatsuya Yoshizawa & Takaichi Fukuda & Kazuya Yamagata & Weikang Cai & Yu, 2022. "Phosphatase protector alpha4 (α4) is involved in adipocyte maintenance and mitochondrial homeostasis through regulation of insulin signaling," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33842-4
    DOI: 10.1038/s41467-022-33842-4
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-33842-4
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-022-33842-4?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Weikang Cai & Masaji Sakaguchi & Andre Kleinridders & Gonzalo Gonzalez-Del Pino & Jonathan M. Dreyfuss & Brian T. O’Neill & Alfred K. Ramirez & Hui Pan & Jonathon N. Winnay & Jeremie Boucher & Michael, 2017. "Domain-dependent effects of insulin and IGF-1 receptors on signalling and gene expression," Nature Communications, Nature, vol. 8(1), pages 1-14, April.
    2. Masaji Sakaguchi & Weikang Cai & Chih-Hao Wang & Carly T. Cederquist & Marcos Damasio & Erica P. Homan & Thiago Batista & Alfred K. Ramirez & Manoj K. Gupta & Martin Steger & Nicolai J. Wewer Albrecht, 2019. "FoxK1 and FoxK2 in insulin regulation of cellular and mitochondrial metabolism," Nature Communications, Nature, vol. 10(1), pages 1-17, December.
    3. Brian C. Searle & Lindsay K. Pino & Jarrett D. Egertson & Ying S. Ting & Robert T. Lawrence & Brendan X. MacLean & Judit Villén & Michael J. MacCoss, 2018. "Chromatogram libraries improve peptide detection and quantification by data independent acquisition mass spectrometry," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
    4. Jeremie Boucher & Marcelo A. Mori & Kevin Y. Lee & Graham Smyth & Chong Wee Liew & Yazmin Macotela & Michael Rourk & Matthias Bluher & Steven J. Russell & C. Ronald Kahn, 2012. "Impaired thermogenesis and adipose tissue development in mice with fat-specific disruption of insulin and IGF-1 signalling," Nature Communications, Nature, vol. 3(1), pages 1-11, January.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Shota Okagawa & Masaji Sakaguchi & Yuma Okubo & Yuri Takekuma & Motoyuki Igata & Tatsuya Kondo & Naoki Takeda & Kimi Araki & Bruna Brasil Brandao & Wei-Jun Qian & Yu-Hua Tseng & Rohit N. Kulkarni & Na, 2024. "Hepatic SerpinA1 improves energy and glucose metabolism through regulation of preadipocyte proliferation and UCP1 expression," Nature Communications, Nature, vol. 15(1), pages 1-19, December.

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Shota Okagawa & Masaji Sakaguchi & Yuma Okubo & Yuri Takekuma & Motoyuki Igata & Tatsuya Kondo & Naoki Takeda & Kimi Araki & Bruna Brasil Brandao & Wei-Jun Qian & Yu-Hua Tseng & Rohit N. Kulkarni & Na, 2024. "Hepatic SerpinA1 improves energy and glucose metabolism through regulation of preadipocyte proliferation and UCP1 expression," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    2. Hirofumi Nagao & Ashok Kumar Jayavelu & Weikang Cai & Hui Pan & Jonathan M. Dreyfuss & Thiago M. Batista & Bruna B. Brandão & Matthias Mann & C. Ronald Kahn, 2023. "Unique ligand and kinase-independent roles of the insulin receptor in regulation of cell cycle, senescence and apoptosis," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    3. Fengchao Yu & Guo Ci Teo & Andy T. Kong & Klemens Fröhlich & Ginny Xiaohe Li & Vadim Demichev & Alexey I. Nesvizhskii, 2023. "Analysis of DIA proteomics data using MSFragger-DIA and FragPipe computational platform," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    4. Ray Sajulga & Caleb Easterly & Michael Riffle & Bart Mesuere & Thilo Muth & Subina Mehta & Praveen Kumar & James Johnson & Bjoern Andreas Gruening & Henning Schiebenhoefer & Carolin A Kolmeder & Steph, 2020. "Survey of metaproteomics software tools for functional microbiome analysis," PLOS ONE, Public Library of Science, vol. 15(11), pages 1-20, November.
    5. Zhi Huang & Gennifer E. Merrihew & Eric B. Larson & Jea Park & Deanna Plubell & Edward J. Fox & Kathleen S. Montine & Caitlin S. Latimer & C. Dirk Keene & James Y. Zou & Michael J. MacCoss & Thomas J., 2023. "Brain proteomic analysis implicates actin filament processes and injury response in resilience to Alzheimer’s disease," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    6. Digant Nayak & Dongwen Lv & Yaxia Yuan & Peiyi Zhang & Wanyi Hu & Anindita Nayak & Eliza A. Ruben & Zongyang Lv & Patrick Sung & Robert Hromas & Guangrong Zheng & Daohong Zhou & Shaun K. Olsen, 2024. "Development and crystal structures of a potent second-generation dual degrader of BCL-2 and BCL-xL," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    7. Marziah Hashimi & T. Andrew Sebrell & Jodi F. Hedges & Deann Snyder & Katrina N. Lyon & Stephanie D. Byrum & Samuel G. Mackintosh & Dan Crowley & Michelle D. Cherne & David Skwarchuk & Amanda Robison , 2023. "Antiviral responses in a Jamaican fruit bat intestinal organoid model of SARS-CoV-2 infection," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    8. Rafaela Muniz de Queiroz & Gizem Efe & Asja Guzman & Naoko Hashimoto & Yusuke Kawashima & Tomoaki Tanaka & Anil K. Rustgi & Carol Prives, 2024. "Mdm2 requires Sprouty4 to regulate focal adhesion formation and metastasis independent of p53," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    9. Klemens Fröhlich & Eva Brombacher & Matthias Fahrner & Daniel Vogele & Lucas Kook & Niko Pinter & Peter Bronsert & Sylvia Timme-Bronsert & Alexander Schmidt & Katja Bärenfaller & Clemens Kreutz & Oliv, 2022. "Benchmarking of analysis strategies for data-independent acquisition proteomics using a large-scale dataset comprising inter-patient heterogeneity," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    10. Francois Moreau & Nicholas S. Kirk & Fa Zhang & Vasily Gelfanov & Edward O. List & Martina Chrudinová & Hari Venugopal & Michael C. Lawrence & Veronica Jimenez & Fatima Bosch & John J. Kopchick & Rich, 2022. "Interaction of a viral insulin-like peptide with the IGF-1 receptor produces a natural antagonist," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    11. Valdemaras Petrosius & Pedro Aragon-Fernandez & Nil Üresin & Gergo Kovacs & Teeradon Phlairaharn & Benjamin Furtwängler & Jeff Op De Beeck & Sarah L. Skovbakke & Steffen Goletz & Simon Francis Thomsen, 2023. "Exploration of cell state heterogeneity using single-cell proteomics through sensitivity-tailored data-independent acquisition," Nature Communications, Nature, vol. 14(1), pages 1-16, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33842-4. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.