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
  • 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. [email protected].
  • # 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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