The DMH <sup>GABA</sup> Neurons Play a Crucial Role in the Regulation of Cold‐Induced White Adipose Browning through DMH to LPO Projection
The browning of white adipose tissue (WAT) can convert energy-storing WAT into energy-dissipating beige adipose tissue to combat obesity and metabolic dysfunction. Cold exposure is a WAT browning-inducing condition in mice. Hypothalamus regulates WAT browning. However, the mechanism of central regulation of WAT browning is still elusive. Here, it is reported that GABAergic neurons in the dorsomedial hypothalamus (DMH<sup>GABA</sup> neurons) are activated in response to cold exposure. Designer receptors exclusively activated by designer drugs (DREADDs) activation of DMH<sup>GABA</sup> neurons elicited WAT browning, increased energy expenditure, lowered fat mass weights, and body weight. Conversely, inactivation of DMH<sup>GABA</sup> neurons showed the opposite effects. Cell type-specific anterograde tracing revealed that DMH<sup>GABA</sup> neurons projected to the lateral preoptic area (LPO). Chemogenetic and optogenetic functional circuit interrogation demonstrated that the activation of this projection induced WAT browning. Together, it is uncovered that DMH<sup>GABA</sup> neurons may act as a key neuronal population controlling cold exposure-induced WAT browning. DMH<sup>GABA</sup> neurons regulate WAT browning through DMH to LPO projection. This study expands the understanding of the central mechanism governing the white adipose browning, as well as the anti-obesity effects of cold therapy.
Authors
- Qian Zhou (ORCID: https://orcid.org/0000-0002-1828-4879)
- Zhijie Su (ORCID: https://orcid.org/0000-0003-4476-5569)
- Bingwei Wang (ORCID: https://orcid.org/0000-0001-7391-4784)
- Yujia Hou
- Ruimao Zheng (ORCID: https://orcid.org/0000-0001-7404-2607)
- Chenyu Zhang (ORCID: https://orcid.org/0000-0001-7722-617X)
- Jiarui Liu (ORCID: https://orcid.org/0000-0003-1881-1971)
- Weiguang Zhang (ORCID: https://orcid.org/0000-0001-5055-4907)
- Wei L. Shen (ORCID: https://orcid.org/0000-0002-3785-2245)
- Lihua Qin (ORCID: https://orcid.org/0000-0002-8821-9394)
- Xiangyang Xie (ORCID: https://orcid.org/0000-0003-4317-7327)
- Wen Yang
- Miao Zhao (ORCID: https://orcid.org/0009-0003-3607-5215)
- Bingbing Guo
- Xiaoning Yang
Institutions
- Peking University (CN)
- National Health and Family Planning Commission (CN)
- Southwest Medical University (CN)
- ShanghaiTech University (CN)
- Ministry of Education (RO)
- Ministry of Education (ME)
- Beijing Academy of Science and Technology (CN)
- Tianjin Medical University (CN)
Publication Details
- Journal
- Advanced Science
- Published
- 2025-11-05
- DOI
- https://doi.org/10.1002/advs.202508513
- Citations
- 1
- Primary Topic
- Adipose Tissue and Metabolism
- Type
- article
- Field-Weighted Citation Impact
- 1.16
Funders
- Yale University
- University of Washington
- University of Texas Southwestern Medical Center
- National University of Singapore
- National Natural Science Foundation of China
- University of Hong Kong
- Peking University
- University of Science and Technology of China
- ShanghaiTech University
- National Science and Technology Major Project
- Directorate for Biological Sciences
- University of California, San Francisco
- Tufts University School of Medicine
- National Key Research and Development Program of China
- Universitätsklinikum Hamburg-Eppendorf