TH-positive pulmonary nerve fiber-epithelial interaction promotes adipose thermogenesis in male mice
Cold exposure activates sympathetic neurons in adipose tissue to maintain thermal homeostasis. However, whether sympathetic activation in non-adipose tissues contributes to cross-organ regulation of adipose thermogenesis remains unclear. Here, we demonstrate the activation of TH-positive pulmonary nerve fibers (TPNFs) by cold exposure, which further promotes adipose thermogenesis. Specifically, cold exposure activates TPNFs that innervate bronchial Club cells in the lung and leads to a reduction in Secretoglobin family 3A member 1 (SCGB3A1) expression via Adrenergic Receptor β2 (ADRB2). SCGB3A1, a Club cell-specific secretory factor, binds the choline transporter SLC44A2 on adipocytes to restrict choline uptake and impair thermogenic activation. Meanwhile, TPNFs activation induces NGF secretion from Club cells, which in turn strengthens TPNFs innervation of Club cells in a feedforward loop. Importantly, the stimulation of this mechanism via tracheal infusion of the ADRB2 agonist norepinephrine (NE) enhances thermogenesis in mice. Jiang et al. reveal a lung–adipose communication pathway in which cold-activated TH-positive pulmonary nerve fibers regulate Club cell SCGB3A1 secretion to control adipocyte choline uptake and thermogenesis.
Authors
- Anke Zhang (ORCID: https://orcid.org/0000-0002-0007-7724)
- Houshi Xu (ORCID: https://orcid.org/0000-0002-2878-0913)
- Zhen‐Ning Zhang (ORCID: https://orcid.org/0000-0003-3798-7104)
- Junkun Jiang
- Bing Luan (ORCID: https://orcid.org/0000-0002-0409-2964)
- Wenjing Yu (ORCID: https://orcid.org/0009-0004-5356-4034)
- Donglei Zhou (ORCID: https://orcid.org/0000-0002-9974-8689)
- Wenlong Wu
- Chengrui Liang
- ANQI DONG
- Xinran Wang (ORCID: https://orcid.org/0009-0008-7230-3445)
- Junfeng Han
- Lei Du
- Zhangming Lu
- Chuan Zhang
- Yonghao Zhou
- Ling Yuan
Institutions
- Tongji University (CN)
- Shanghai Medical College of Fudan University (CN)
- Shanghai Jiao Tong University (CN)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Fudan University (CN)
- Peking Union Medical College Hospital (CN)
- Fudan University Shanghai Cancer Center (CN)
- Shanghai Tenth People's Hospital (CN)
- Second Affiliated Hospital of Zhejiang University (CN)
- Zhejiang University (CN)
Publication Details
- Journal
- Nature Communications
- Published
- 2026-11-02
- DOI
- https://doi.org/10.1038/s41467-026-79317-8
- Primary Topic
- Adipose Tissue and Metabolism
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Natural Science Foundation of China
- China Postdoctoral Science Foundation
- Chinese Academy of Medical Sciences
- Nanjing Medical University
- Peking Union Medical College Hospital
- Peking Union Medical College
- ShanghaiTech University
- National Science and Technology Major Project