Tongji University team: cold activates lung nerve fibers and adipose thermogenesis in male mice

A research group from Tongji University in Shanghai and partner institutions reported that cold exposure activates TH-positive pulmonary nerve fibers (TPNFs) in male mice, and that this activation promotes thermogenesis in adipose tissue. The study was published in Nature Communications on 2 November 2026. nature.comNature Communicationsnature.comOpen source ↗ Cold is known to activate sympathetic neurons in adipose tissue to maintain thermal homeostasis. Whether sympathetic activation in non-adipose tissues contributes to cross-organ regulation of adipose thermogenesis had remained unclear.

TPNFs, Club cells and SCGB3A1

According to the authors, TPNFs innervate bronchial Club cells in the lung. Cold exposure activates these fibers and leads to a reduction in expression of Secretoglobin family 3A member 1 (SCGB3A1) in Club cells, acting through Adrenergic Receptor β2 (ADRB2).

SCGB3A1 is a secretory factor specific to Club cells. The authors report that it binds the choline transporter SLC44A2 on adipocytes, which restricts choline uptake and impairs thermogenic activation. Under cold exposure, the fall in SCGB3A1 expression is therefore part of the pathway that promotes adipose thermogenesis. The work used mouse lines with Club cell-targeted Cre drivers, CC10-Cre and CC10-CreERT2, the latter combined with the mTmG reporter.

Feedforward loop and tracheal norepinephrine

TPNF activation also induces NGF secretion from Club cells. NGF in turn strengthens TPNF innervation of Club cells, forming a feedforward loop. nature.comNature Communicationsnature.comOpen source ↗

To stimulate this mechanism, the authors infused the ADRB2 agonist norepinephrine (NE) into the trachea of mice. This enhanced thermogenesis. All results described relate to experiments in mice; the study title specifies male mice.

The corresponding authors are Junfeng Han, Zhen-Ning Zhang and Bing Luan.