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

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 () and Xiangyang Xie ()
Additional contact information
Mingming Xing: Tianjin Medical University
Yang Li: 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
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
Xiangyang Xie: Tianjin Medical University

Nature Communications, 2024, vol. 15, issue 1, 1-21

Abstract: 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.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-53258-6 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-53258-6

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-53258-6

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().