Paraventricular nucleus–locus coeruleus VGlut2 neural circuit regulates energy metabolism in mice
The role of the central nervous system in energy homoeostasis remains unclear. This study examined the role of VGlut2-expressing neurons in the paraventricular nucleus of the hypothalamus (PVH<sup>VGlut2</sup>) and their downstream circuits in the regulation of energy homoeostasis. Long-term high-fat diet (HFD) disrupts energy balance and compensatorily activates PVH<sup>VGlut2</sup> neurons that innervate interscapular brown adipose tissue (iBAT). These neurons are inhibited during food consumption, suggesting their involvement in feeding and energy metabolism regulation. Activation of PVH<sup>VGlut2</sup> neurons reduces food intake and enhances iBAT thermogenesis. Further, optogenetic PVH<sup>VGlut2</sup>→ locus coeruleus (LC) circuit activation inhibited feeding and elevated iBAT temperature, which was blocked by sympathetic nerve denervation. Long-term chemogenetic PVH<sup>VGlut2</sup> → LC neural circuit activation ameliorates HFD-induced obesity and insulin resistance. The PVH<sup>VGlut2</sup> → LC circuit integrates feeding inhibition and peripheral thermogenesis signals to regulate energy metabolism, offering potential intervention targets for obesity and other energy homoeostasis disorders.
Authors
- Jiaxin Fan (ORCID: https://orcid.org/0000-0002-2883-9946)
- Wei Yang (ORCID: https://orcid.org/0000-0001-5719-4393)
- Zelin Zhang
- Hui-Hui Zhu
- Yang He (ORCID: https://orcid.org/0000-0002-7460-5649)
- Guifang Cao (ORCID: https://orcid.org/0000-0002-6177-884X)
- Jiapeng Yin (ORCID: https://orcid.org/0000-0002-1925-4823)
- Chenguang Du (ORCID: https://orcid.org/0000-0002-3548-7512)
- Xin Zhang (ORCID: https://orcid.org/0000-0003-4099-6175)
- Xiaolong Li (ORCID: https://orcid.org/0000-0001-5651-9555)
- Yujie Chen (ORCID: https://orcid.org/0000-0002-9905-9138)
- Yongqiang Li (ORCID: https://orcid.org/0000-0002-8110-8835)
- Shuying Liu (ORCID: https://orcid.org/0000-0002-5573-7574)
- Haodong Liu
- Penghui Li (ORCID: https://orcid.org/0000-0002-2286-7700)
- Jie Ren (ORCID: https://orcid.org/0000-0001-8795-0372)
- Teng Ben-qi (ORCID: https://orcid.org/0000-0002-7062-0753)
- Qinqin Hao
- Haijun Li (ORCID: https://orcid.org/0009-0002-9143-6653)
- M. Yu (ORCID: https://orcid.org/0009-0009-4912-5457)
Institutions
- Inner Mongolia Agricultural University (CN)
- Inner Mongolia University of Science and Technology (CN)
- Inner Mongolia Electric Power (China) (CN)
- Inner Mongolia Electric Power Survey & Design Institute (China) (CN)
- Inner Mongolia Academy of Agricultural & Animal Husbandry Sciences (CN)
- Baotou Teachers College (CN)
- Inner Mongolia Comprehensive Disease Prevention and Control Center (CN)
Publication Details
- Journal
- Cell Death and Disease
- Published
- 2025-12-09
- DOI
- https://doi.org/10.1038/s41419-025-08238-z
- Primary Topic
- Regulation of Appetite and Obesity
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Natural Science Foundation of China
- Inner Mongolia Agricultural University