IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-53258-6.html
   My bibliography  Save this article

Paraventricular hypothalamic RUVBL2 neurons suppress appetite by enhancing excitatory synaptic transmission in distinct neurocircuits

Author

Listed:
  • Mingming Xing

    (Tianjin Medical University)

  • Yang Li

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Yuqi Zhang

    (Tianjin Medical University)

  • Juemou Zhou

    (Tianjin Medical University)

  • Danting Ma

    (Tianjin Medical University)

  • Mengqi Zhang

    (Tianjin Medical University)

  • Minglei Tang

    (Tianjin Medical University)

  • Ting Ouyang

    (Tianjin Medical University)

  • Fumiao Zhang

    (Tianjin Medical University)

  • Xiaofeng Shi

    (Tianjin Medical University)

  • Jianyuan Sun

    (University of Chinese Academy of Sciences
    Chinese Academy of Sciences)

  • Zuxin Chen

    (Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions)

  • Weiping J. Zhang

    (Tianjin Medical University)

  • Shuli Zhang

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Xiangyang Xie

    (Tianjin Medical University)

Abstract

The paraventricular hypothalamus (PVH) is crucial for food intake control, yet the presynaptic mechanisms underlying PVH neurons remain unclear. Here, we show that RUVBL2 in the PVH is significantly reduced during energy deficit, and knockout (KO) of PVH RUVBL2 results in hyperphagic obesity in mice. RUVBL2-expressing neurons in the PVH (PVHRUVBL2) exert the anorexigenic effect by projecting to the arcuate hypothalamus, the dorsomedial hypothalamus, and the parabrachial complex. We further demonstrate that PVHRUVBL2 neurons form the synaptic connections with POMC and AgRP neurons in the ARC. PVH RUVBL2 KO impairs the excitatory synaptic transmission by reducing presynaptic boutons and synaptic vesicles near active zone. Finally, RUVBL2 overexpression in the PVH suppresses food intake and protects against diet induced obesity. Together, this study demonstrates an essential role for PVH RUVBL2 in food intake control, and suggests that modulation of synaptic plasticity could be an effective way to curb appetite and obesity.

Suggested Citation

  • Mingming Xing & Yang Li & Yuqi Zhang & Juemou Zhou & Danting Ma & Mengqi Zhang & Minglei Tang & Ting Ouyang & Fumiao Zhang & Xiaofeng Shi & Jianyuan Sun & Zuxin Chen & Weiping J. Zhang & Shuli Zhang &, 2024. "Paraventricular hypothalamic RUVBL2 neurons suppress appetite by enhancing excitatory synaptic transmission in distinct neurocircuits," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-53258-6
    DOI: 10.1038/s41467-024-53258-6
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-53258-6
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-024-53258-6?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. Yasuhiko Minokoshi & Thierry Alquier & Noboru Furukawa & Young-Bum Kim & Anna Lee & Bingzhong Xue & James Mu & Fabienne Foufelle & Pascal Ferré & Morris J. Birnbaum & Bettina J. Stuck & Barbara B. Kah, 2004. "AMP-kinase regulates food intake by responding to hormonal and nutrient signals in the hypothalamus," Nature, Nature, vol. 428(6982), pages 569-574, April.
    2. Martin G. Myers & David P. Olson, 2012. "Central nervous system control of metabolism," Nature, Nature, vol. 491(7424), pages 357-363, November.
    3. G. J. Morton & D. E. Cummings & D. G. Baskin & G. S. Barsh & M. W. Schwartz, 2006. "Central nervous system control of food intake and body weight," Nature, Nature, vol. 443(7109), pages 289-295, September.
    4. Michael A. Cowley & James L. Smart & Marcelo Rubinstein & Marcelo G. Cerdán & Sabrina Diano & Tamas L. Horvath & Roger D. Cone & Malcolm J. Low, 2001. "Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus," Nature, Nature, vol. 411(6836), pages 480-484, May.
    5. Deniz Atasoy & J. Nicholas Betley & Helen H. Su & Scott M. Sternson, 2012. "Deconstruction of a neural circuit for hunger," Nature, Nature, vol. 488(7410), pages 172-177, August.
    6. Wei Fan & Bruce A. Boston & Robert A. Kesterson & Victor J. Hruby & Roger D. Cone, 1997. "Role of melanocortinergic neurons in feeding and the agouti obesity syndrome," Nature, Nature, vol. 385(6612), pages 165-168, January.
    7. Jason Flannick & Josep M. Mercader & Christian Fuchsberger & Miriam S. Udler & Anubha Mahajan & Jennifer Wessel & Tanya M. Teslovich & Lizz Caulkins & Ryan Koesterer & Francisco Barajas-Olmos & Thomas, 2019. "Exome sequencing of 20,791 cases of type 2 diabetes and 24,440 controls," Nature, Nature, vol. 570(7759), pages 71-76, June.
    8. Michael J. Krashes & Bhavik P. Shah & Joseph C. Madara & David P. Olson & David E. Strochlic & Alastair S. Garfield & Linh Vong & Hongjuan Pei & Mitsuko Watabe-Uchida & Naoshige Uchida & Stephen D. Li, 2014. "An excitatory paraventricular nucleus to AgRP neuron circuit that drives hunger," Nature, Nature, vol. 507(7491), pages 238-242, March.
    9. Hui Wang & Boyuan Li & Linyu Zuo & Bo Wang & Yan Yan & Kai Tian & Rong Zhou & Chenlu Wang & Xizi Chen & Yongpeng Jiang & Haonan Zheng & Fangfei Qin & Bin Zhang & Yang Yu & Chao-Pei Liu & Yanhui Xu & J, 2022. "The transcriptional coactivator RUVBL2 regulates Pol II clustering with diverse transcription factors," Nature Communications, Nature, vol. 13(1), pages 1-26, 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. Sheng Qiu & Qinan Wu & Hao Wang & Dongfang Liu & Chen Chen & Zhiming Zhu & Hongting Zheng & Gangyi Yang & Ling Li & Mengliu Yang, 2024. "AZGP1 in POMC neurons modulates energy homeostasis and metabolism through leptin-mediated STAT3 phosphorylation," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    2. Nathan Fearby & Samantha Penman & Panayotis Thanos, 2022. "Effects of Δ9-Tetrahydrocannibinol (THC) on Obesity at Different Stages of Life: A Literature Review," IJERPH, MDPI, vol. 19(6), pages 1-28, March.
    3. Hongli Li & Yuanzhong Xu & Yanyan Jiang & Zhiying Jiang & Joshua Otiz-Guzman & Jessie C. Morrill & Jing Cai & Zhengmei Mao & Yong Xu & Benjamin R. Arenkiel & Cheng Huang & Qingchun Tong, 2023. "The melanocortin action is biased toward protection from weight loss in mice," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    4. Stephan Dodt & Noah V. Widdershooven & Marie-Luise Dreisow & Lisa Weiher & Lukas Steuernagel & F. Thomas Wunderlich & Jens C. Brüning & Henning Fenselau, 2024. "NPY-mediated synaptic plasticity in the extended amygdala prioritizes feeding during starvation," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    5. Takashi Nagashima & Suguru Tohyama & Kaori Mikami & Masashi Nagase & Mieko Morishima & Atsushi Kasai & Hitoshi Hashimoto & Ayako M. Watabe, 2022. "Parabrachial-to-parasubthalamic nucleus pathway mediates fear-induced suppression of feeding in male mice," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    6. Hancheng Mao & Geun Hyang Kim & Linxiu Pan & Ling Qi, 2024. "Regulation of leptin signaling and diet-induced obesity by SEL1L-HRD1 ER-associated degradation in POMC expressing neurons," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    7. Sarah Meulebrouck & Judith Merrheim & Gurvan Queniat & Cyril Bourouh & Mehdi Derhourhi & Mathilde Boissel & Xiaoyan Yi & Alaa Badreddine & Raphaël Boutry & Audrey Leloire & Bénédicte Toussaint & Souhi, 2024. "Functional genetics reveals the contribution of delta opioid receptor to type 2 diabetes and beta-cell function," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    8. Roberto Luca & Stefano Nardone & Kevin P. Grace & Anne Venner & Michela Cristofolini & Sathyajit S. Bandaru & Lauren T. Sohn & Dong Kong & Takatoshi Mochizuki & Bianca Viberti & Lin Zhu & Antonino Zit, 2022. "Orexin neurons inhibit sleep to promote arousal," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    9. Stephanie O. Erjavec & Sahar Gelfman & Alexa R. Abdelaziz & Eunice Y. Lee & Isha Monga & Anna Alkelai & Iuliana Ionita-Laza & Lynn Petukhova & Angela M. Christiano, 2022. "Whole exome sequencing in Alopecia Areata identifies rare variants in KRT82," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    10. Nathan L. Price & Pablo Fernández-Tussy & Luis Varela & Magdalena P. Cardelo & Marya Shanabrough & Binod Aryal & Rafael Cabo & Yajaira Suárez & Tamas L. Horvath & Carlos Fernández-Hernando, 2024. "microRNA-33 controls hunger signaling in hypothalamic AgRP neurons," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    11. Yanine, Franco Fernando & Caballero, Federico I. & Sauma, Enzo E. & Córdova, Felisa M., 2014. "Building sustainable energy systems: Homeostatic control of grid-connected microgrids, as a means to reconcile power supply and energy demand response management," Renewable and Sustainable Energy Reviews, Elsevier, vol. 40(C), pages 1168-1191.
    12. Solomiia Korchynska & Patrick Rebernik & Marko Pende & Laura Boi & Alán Alpár & Ramon Tasan & Klaus Becker & Kira Balueva & Saiedeh Saghafi & Peer Wulff & Tamas L. Horvath & Gilberto Fisone & Hans-Ulr, 2022. "A hypothalamic dopamine locus for psychostimulant-induced hyperlocomotion in mice," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    13. Jennifer P. Nguyen & Timothy D. Arthur & Kyohei Fujita & Bianca M. Salgado & Margaret K. R. Donovan & Hiroko Matsui & Ji Hyun Kim & Agnieszka D’Antonio-Chronowska & Matteo D’Antonio & Kelly A. Frazer, 2023. "eQTL mapping in fetal-like pancreatic progenitor cells reveals early developmental insights into diabetes risk," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    14. Stéphane Leon & Vincent Simon & Thomas H. Lee & Lukas Steuernagel & Samantha Clark & Nasim Biglari & Thierry Lesté-Lasserre & Nathalie Dupuy & Astrid Cannich & Luigi Bellocchio & Philippe Zizzari & Ca, 2024. "Single cell tracing of Pomc neurons reveals recruitment of ‘Ghost’ subtypes with atypical identity in a mouse model of obesity," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    15. Jing Yan & Yuemei Zhang & Hairong Yu & Yicen Zong & Daixi Wang & Jiangfei Zheng & Li Jin & Xiangtian Yu & Caizhi Liu & Yi Zhang & Feng Jiang & Rong Zhang & Xiangnan Fang & Ting Xu & Mingyu Li & Jianzh, 2022. "GPSM1 impairs metabolic homeostasis by controlling a pro-inflammatory pathway in macrophages," Nature Communications, Nature, vol. 13(1), pages 1-22, December.
    16. Hermanussen, M. & Tresguerres, J.A.F., 2005. "A new anti-obesity drug treatment: First clinical evidence that, antagonising glutamate-gated Ca2+ ion channels with memantine normalises binge-eating disorders," Economics & Human Biology, Elsevier, vol. 3(2), pages 329-337, July.
    17. Aimee M. Deaton & Aditi Dubey & Lucas D. Ward & Peter Dornbos & Jason Flannick & Elaine Yee & Simina Ticau & Leila Noetzli & Margaret M. Parker & Rachel A. Hoffing & Carissa Willis & Mollie E. Plekan , 2022. "Rare loss of function variants in the hepatokine gene INHBE protect from abdominal obesity," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    18. Alena A. Nikanorova & Nikolay A. Barashkov & Sergey S. Nakhodkin & Vera G. Pshennikova & Aisen V. Solovyev & Georgii P. Romanov & Sargylana S. Kuzmina & Nikolay N. Sazonov & Tatyana E. Burtseva & Jon , 2020. "The Role of Leptin Levels in Adaptation to Cold Climates," IJERPH, MDPI, vol. 17(6), pages 1-13, March.
    19. Jennifer L. Halford & Valerie N. Morrill & Seung Hoan Choi & Sean J. Jurgens & Giorgio Melloni & Nicholas A. Marston & Lu-Chen Weng & Victor Nauffal & Amelia W. Hall & Sophia Gunn & Christina A. Austi, 2022. "Endophenotype effect sizes support variant pathogenicity in monogenic disease susceptibility genes," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    20. Michael M Swarbrick & Björn Waldenmaier & Len A Pennacchio & Denise L Lind & Martha M Cavazos & Frank Geller & Raphael Merriman & Anna Ustaszewska & Mary Malloy & André Scherag & Wen-Chi Hsueh & Winfr, 2005. "Lack of Support for the Association between GAD2 Polymorphisms and Severe Human Obesity," PLOS Biology, Public Library of Science, vol. 3(9), pages 1-1, August.

    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:15:y:2024:i:1:d:10.1038_s41467-024-53258-6. 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.