2. Academic Validation
  3. Paraventricular hypothalamic RUVBL2 neurons suppress appetite by enhancing excitatory synaptic transmission in distinct neurocircuits

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

  • Nat Commun. 2024 Oct 16;15(1):8939. doi: 10.1038/s41467-024-53258-6.
Mingming Xing # 1,  Yang Li # 2 3,  Yuqi Zhang # 1,  Juemou Zhou # 1,  Danting Ma 1,  Mengqi Zhang 1,  Minglei Tang 1,  Ting Ouyang 1,  Fumiao Zhang 1,  Xiaofeng Shi 1,  Jianyuan Sun 3 4,  Zuxin Chen 5,  Weiping J Zhang 1,  Shuli Zhang 6 7,  Xiangyang Xie 8
Affiliations

Affiliations

  • 1 NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, The province and ministry co-sponsored collaborative innovation center for medical epigenetics, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, 300134, China.
  • 2 State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
  • 3 University of Chinese Academy of Sciences, Beijing, 100049, China.
  • 4 The Brain Cognition and Brain Disease Institute, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China.
  • 5 Shenzhen Key Laboratory of Drug Addiction, Shenzhen Neher Neural Plasticity Laboratory, Brain Cognition and Brain Disease Institute, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen, 518055, China.
  • 6 State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China. shulizhang@ibp.ac.cn.
  • 7 University of Chinese Academy of Sciences, Beijing, 100049, China. shulizhang@ibp.ac.cn.
  • 8 NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, The province and ministry co-sponsored collaborative innovation center for medical epigenetics, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, 300134, China. xyxie@tmu.edu.cn.
  • # Contributed equally.
PMID: 39414808 DOI: 10.1038/s41467-024-53258-6
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.

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