IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-43021-8.html
   My bibliography  Save this article

Transcriptional repression of beige fat innervation via a YAP/TAZ-S100B axis

Author

Listed:
  • Xun Huang

    (Peking University
    Peking University
    Peking University)

  • Xinmeng Li

    (Peking University)

  • Hongyu Shen

    (Peking University
    Peking University
    Peking University)

  • Yiheng Zhao

    (Peking University
    Peking University
    Peking University)

  • Zhao Zhou

    (Peking University)

  • Yushuang Wang

    (Peking University)

  • Jingfei Yao

    (Peking University)

  • Kaili Xue

    (Peking University)

  • Dongmei Wu

    (Peking University
    Peking University)

  • Yifu Qiu

    (Peking University
    Peking University)

Abstract

Sympathetic innervation is essential for the development of functional beige fat that maintains body temperature and metabolic homeostasis, yet the molecular mechanisms controlling this innervation remain largely unknown. Here, we show that adipocyte YAP/TAZ inhibit sympathetic innervation of beige fat by transcriptional repression of neurotropic factor S100B. Adipocyte-specific loss of Yap/Taz induces S100b expression to stimulate sympathetic innervation and biogenesis of functional beige fat both in subcutaneous white adipose tissue (WAT) and browning-resistant visceral WAT. Mechanistically, YAP/TAZ compete with C/EBPβ for binding to the zinc finger-2 domain of PRDM16 to suppress S100b transcription, which is released by adrenergic-stimulated YAP/TAZ phosphorylation and inactivation. Importantly, Yap/Taz loss in adipocytes or AAV-S100B overexpression in visceral WAT restricts both age-associated and diet-induced obesity, and improves metabolic homeostasis by enhancing energy expenditure of mice. Together, our data reveal that YAP/TAZ act as a brake on the beige fat innervation by blocking PRDM16-C/EBPβ-mediated S100b expression.

Suggested Citation

  • Xun Huang & Xinmeng Li & Hongyu Shen & Yiheng Zhao & Zhao Zhou & Yushuang Wang & Jingfei Yao & Kaili Xue & Dongmei Wu & Yifu Qiu, 2023. "Transcriptional repression of beige fat innervation via a YAP/TAZ-S100B axis," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43021-8
    DOI: 10.1038/s41467-023-43021-8
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-43021-8
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-43021-8?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. Hongyu Shen & Xun Huang & Yiheng Zhao & Dongmei Wu & Kaili Xue & Jingfei Yao & Yushuang Wang & Nan Tang & Yifu Qiu, 2022. "The Hippo pathway links adipocyte plasticity to adipose tissue fibrosis," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    2. Patrick Seale & Bryan Bjork & Wenli Yang & Shingo Kajimura & Sherry Chin & Shihuan Kuang & Anthony Scimè & Srikripa Devarakonda & Heather M. Conroe & Hediye Erdjument-Bromage & Paul Tempst & Michael A, 2008. "PRDM16 controls a brown fat/skeletal muscle switch," Nature, Nature, vol. 454(7207), pages 961-967, August.
    3. Xing Zeng & Mengchen Ye & Jon M. Resch & Mark P. Jedrychowski & Bo Hu & Bradford B. Lowell & David D. Ginty & Bruce M. Spiegelman, 2019. "Publisher Correction: Innervation of thermogenic adipose tissue via a calsyntenin 3β–S100b axis," Nature, Nature, vol. 570(7760), pages 32-32, June.
    4. Elisa Duregotti & Christina M. Reumiller & Ursula Mayr & Maria Hasman & Lukas E. Schmidt & Sean A. Burnap & Konstantinos Theofilatos & Javier Barallobre-Barreiro & Arne Beran & Maria Grandoch & Alessa, 2022. "Reduced secretion of neuronal growth regulator 1 contributes to impaired adipose-neuronal crosstalk in obesity," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    5. Qiang Wang & Huixia Li & Kazuki Tajima & Anthony R. P. Verkerke & Zachary H. Taxin & Zhishuai Hou & Joanne B. Cole & Fei Li & Jake Wong & Ichitaro Abe & Rachana N. Pradhan & Tadashi Yamamuro & Takeshi, 2022. "Post-translational control of beige fat biogenesis by PRDM16 stabilization," Nature, Nature, vol. 609(7925), pages 151-158, September.
    6. Xing Zeng & Mengchen Ye & Jon M. Resch & Mark P. Jedrychowski & Bo Hu & Bradford B. Lowell & David D. Ginty & Bruce M. Spiegelman, 2019. "Innervation of thermogenic adipose tissue via a calsyntenin 3β–S100b axis," Nature, Nature, vol. 569(7755), pages 229-235, May.
    7. Shingo Kajimura & Patrick Seale & Kazuishi Kubota & Elaine Lunsford & John V. Frangioni & Steven P. Gygi & Bruce M. Spiegelman, 2009. "Initiation of myoblast to brown fat switch by a PRDM16–C/EBP-β transcriptional complex," Nature, Nature, vol. 460(7259), pages 1154-1158, August.
    8. Tim J. Schulz & Ping Huang & Tian Lian Huang & Ruidan Xue & Lindsay E. McDougall & Kristy L. Townsend & Aaron M. Cypess & Yuji Mishina & Emanuela Gussoni & Yu-Hua Tseng, 2013. "Brown-fat paucity due to impaired BMP signalling induces compensatory browning of white fat," Nature, Nature, vol. 495(7441), pages 379-383, March.
    9. Xin Cui & Jia Jing & Rui Wu & Qiang Cao & Fenfen Li & Ke Li & Shirong Wang & Liqing Yu & Gary Schwartz & Huidong Shi & Bingzhong Xue & Hang Shi, 2021. "Adipose tissue-derived neurotrophic factor 3 regulates sympathetic innervation and thermogenesis in adipose tissue," Nature Communications, Nature, vol. 12(1), pages 1-18, December.
    10. Lei Wang & ShengPeng Wang & Yue Shi & Rui Li & Stefan Günther & Yu Ting Ong & Michael Potente & Zuyi Yuan & Enqi Liu & Stefan Offermanns, 2020. "YAP and TAZ protect against white adipocyte cell death during obesity," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
    Full references (including those not matched with items on IDEAS)

    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. Elisa Duregotti & Christina M. Reumiller & Ursula Mayr & Maria Hasman & Lukas E. Schmidt & Sean A. Burnap & Konstantinos Theofilatos & Javier Barallobre-Barreiro & Arne Beran & Maria Grandoch & Alessa, 2022. "Reduced secretion of neuronal growth regulator 1 contributes to impaired adipose-neuronal crosstalk in obesity," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    2. Fenfen Li & Jia Jing & Miranda Movahed & Xin Cui & Qiang Cao & Rui Wu & Ziyue Chen & Liqing Yu & Yi Pan & Huidong Shi & Hang Shi & Bingzhong Xue, 2021. "Epigenetic interaction between UTX and DNMT1 regulates diet-induced myogenic remodeling in brown fat," Nature Communications, Nature, vol. 12(1), pages 1-22, December.
    3. Tatsuya Yoshizawa & Yoshifumi Sato & Shihab U. Sobuz & Tomoya Mizumoto & Tomonori Tsuyama & Md. Fazlul Karim & Keishi Miyata & Masayoshi Tasaki & Masaya Yamazaki & Yuichi Kariba & Norie Araki & Eiichi, 2022. "SIRT7 suppresses energy expenditure and thermogenesis by regulating brown adipose tissue functions in mice," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    4. Jiamin Qiu & Feng Yue & Peipei Zhu & Jingjuan Chen & Fan Xu & Lijia Zhang & Kun Ho Kim & Madigan M. Snyder & Nanjian Luo & Hao-wei Xu & Fang Huang & W. Andy Tao & Shihuan Kuang, 2023. "FAM210A is essential for cold-induced mitochondrial remodeling in brown adipocytes," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    5. Yaechan Song & Heeju Na & Seung Eon Lee & You Min Kim & Jihyun Moon & Tae Wook Nam & Yul Ji & Young Jin & Jae Hyung Park & Seok Chan Cho & Jaehoon Lee & Daehee Hwang & Sang-Jun Ha & Hyun Woo Park & Ja, 2024. "Dysfunctional adipocytes promote tumor progression through YAP/TAZ-dependent cancer-associated adipocyte transformation," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    6. Zimeng Xin & Tianying Zhang & Qinyue Lu & Zhangping Yang & Zhi Chen, 2022. "Progress of m 6 A Methylation in Lipid Metabolism in Humans and Animals," Agriculture, MDPI, vol. 12(10), pages 1-18, October.
    7. Yong Geun Jeon & Hahn Nahmgoong & Jiyoung Oh & Dabin Lee & Dong Wook Kim & Jane Eunsoo Kim & Ye Young Kim & Yul Ji & Ji Seul Han & Sung Min Kim & Jee Hyung Sohn & Won Taek Lee & Sun Won Kim & Jeu Park, 2024. "Ubiquitin ligase RNF20 coordinates sequential adipose thermogenesis with brown and beige fat-specific substrates," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    8. Rui Li & Jingchen Shao & Young-June Jin & Haruya Kawase & Yu Ting Ong & Kerstin Troidl & Qi Quan & Lei Wang & Remy Bonnavion & Astrid Wietelmann & Francoise Helmbacher & Michael Potente & Johannes Gra, 2023. "Endothelial FAT1 inhibits angiogenesis by controlling YAP/TAZ protein degradation via E3 ligase MIB2," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    9. Hyuek Jong Lee & Jueun Lee & Myung Jin Yang & Young-Chan Kim & Seon Pyo Hong & Jung Mo Kim & Geum-Sook Hwang & Gou Young Koh, 2023. "Endothelial cell-derived stem cell factor promotes lipid accumulation through c-Kit-mediated increase of lipogenic enzymes in brown adipocytes," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    10. Yan-Ting Chen & Qi-Yuan Yang & Yun Hu & Xiang-Dong Liu & Jeanene M. Avila & Mei-Jun Zhu & Peter W. Nathanielsz & Min Du, 2021. "Imprinted lncRNA Dio3os preprograms intergenerational brown fat development and obesity resistance," Nature Communications, Nature, vol. 12(1), pages 1-18, December.
    11. Hugo Croizer & Rana Mhaidly & Yann Kieffer & Geraldine Gentric & Lounes Djerroudi & Renaud Leclere & Floriane Pelon & Catherine Robley & Mylene Bohec & Arnaud Meng & Didier Meseure & Emanuela Romano &, 2024. "Deciphering the spatial landscape and plasticity of immunosuppressive fibroblasts in breast cancer," Nature Communications, Nature, vol. 15(1), pages 1-28, December.
    12. Suyang Wu & Chen Qiu & Jiahao Ni & Wenli Guo & Jiyuan Song & Xingyin Yang & Yulin Sun & Yanjun Chen & Yunxia Zhu & Xiaoai Chang & Peng Sun & Chunxia Wang & Kai Li & Xiao Han, 2024. "M2 macrophages independently promote beige adipogenesis via blocking adipocyte Ets1," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    13. Xu Feng & Liwen Wang & Ruoyu Zhou & Rui Zhou & Linyun Chen & Hui Peng & Yan Huang & Qi Guo & Xianghang Luo & Haiyan Zhou, 2023. "Senescent immune cells accumulation promotes brown adipose tissue dysfunction during aging," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    14. Yusuke Adachi & Kazutaka Ueda & Seitaro Nomura & Kaoru Ito & Manami Katoh & Mikako Katagiri & Shintaro Yamada & Masaki Hashimoto & Bowen Zhai & Genri Numata & Akira Otani & Munetoshi Hinata & Yuta Hir, 2022. "Beiging of perivascular adipose tissue regulates its inflammation and vascular remodeling," Nature Communications, Nature, vol. 13(1), pages 1-14, 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:14:y:2023:i:1:d:10.1038_s41467-023-43021-8. 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.