Paraventricular hypothalamic RUVBL2 neurons suppress appetite by enhancing excitatory synaptic transmission in distinct neurocircuits
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 (PVH<sup>RUVBL2</sup>) exert the anorexigenic effect by projecting to the arcuate hypothalamus, the dorsomedial hypothalamus, and the parabrachial complex. We further demonstrate that PVH<sup>RUVBL2</sup> 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.
Authors
- Minglei Tang (ORCID: https://orcid.org/0009-0002-4889-0543)
- Weiping J. Zhang (ORCID: https://orcid.org/0000-0003-4727-2380)
- Ting Ouyang (ORCID: https://orcid.org/0000-0002-1127-6016)
- Fumiao Zhang (ORCID: https://orcid.org/0000-0002-7336-8506)
- Xiaofeng Shi (ORCID: https://orcid.org/0000-0002-0357-6967)
- Zuxin Chen (ORCID: https://orcid.org/0000-0002-5412-3140)
- Shuli Zhang (ORCID: https://orcid.org/0000-0001-8006-1134)
- Mingming Xing
- Danting Ma
- Jinsong Zhou (ORCID: https://orcid.org/0000-0001-7688-4373)
- Yuqi Zhang (ORCID: https://orcid.org/0000-0002-8564-0319)
- Yang Li (ORCID: https://orcid.org/0000-0003-2845-5739)
- Mengqi Zhang (ORCID: https://orcid.org/0000-0003-2090-6320)
- Jianyuan Sun
- Xiangyang Xie (ORCID: https://orcid.org/0000-0003-4317-7327)
Institutions
- Chinese Academy of Sciences (CN)
- HKUST Shenzhen Research Institute (CN)
- Institute of Biophysics (CN)
- Shenzhen Institutes of Advanced Technology (CN)
- University of Chinese Academy of Sciences (CN)
- Tianjin Medical University (CN)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-10-16
- DOI
- https://doi.org/10.1038/s41467-024-53258-6
- Citations
- 13
- Primary Topic
- Regulation of Appetite and Obesity
- Type
- article
- Field-Weighted Citation Impact
- 3.56
Funders
- National Natural Science Foundation of China
- Chinese Academy of Sciences
- Fudan University
- Nanjing Medical University
- University of Science and Technology of China
- Tianjin Science and Technology Committee
- National Key Research and Development Program of China
- National Natural Science Foundation of China-Guangdong Joint Fund
- Institute of Biophysics, Chinese Academy of Sciences