2. Academic Validation
  3. Thermogenic adipocyte-derived zinc promotes sympathetic innervation in male mice

Thermogenic adipocyte-derived zinc promotes sympathetic innervation in male mice

  • Nat Metab. 2023 Mar 6. doi: 10.1038/s42255-023-00751-9.
Junkun Jiang # 1,  Donglei Zhou # 2 3,  Anke Zhang # 4,  Wenjing Yu # 1,  Lei Du 5,  Huiwen Yuan 1,  Chuan Zhang 1,  Zelin Wang 1,  Xuyang Jia 5,  Zhen-Ning Zhang 6,  Bing Luan 7
Affiliations

Affiliations

  • 1 Department of Endocrinology, Tongji Hospital Affiliated to Tongji University School of Medicine, Tongji University, Shanghai, China.
  • 2 Department of Gastric Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.
  • 3 Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
  • 4 Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
  • 5 Department of Metabolic Surgery, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
  • 6 Translational Medical Center for Stem Cell Therapy & Institute for Regenerative Medicine, Shanghai East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, China.
  • 7 Department of Endocrinology, Tongji Hospital Affiliated to Tongji University School of Medicine, Tongji University, Shanghai, China. bluan@tongji.edu.cn.
  • # Contributed equally.
PMID: 36879120 DOI: 10.1038/s42255-023-00751-9
Abstract

Sympathetic neurons activate thermogenic adipocytes through release of catecholamine; however, the regulation of sympathetic innervation by thermogenic adipocytes is unclear. Here, we identify primary zinc ion (Zn) as a thermogenic adipocyte-secreted factor that promotes sympathetic innervation and thermogenesis in brown adipose tissue and subcutaneous white adipose tissue in male mice. Depleting thermogenic adipocytes or antagonizing β3-adrenergic receptor on adipocytes impairs sympathetic innervation. In obesity, inflammation-induced upregulation of Zn chaperone protein metallothionein-2 decreases Zn secretion from thermogenic adipocytes and leads to decreased energy expenditure. Furthermore, Zn supplementation ameliorates obesity by promoting sympathetic neuron-induced thermogenesis, while sympathetic denervation abrogates this antiobesity effect. Thus, we have identified a positive feedback mechanism for the reciprocal regulation of thermogenic adipocytes and sympathetic neurons. This mechanism is important for adaptive thermogenesis and could serve as a potential target for the treatment of obesity.

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