The hepatokine Tsukushi gates energy expenditure via brown fat sympathetic innervation

Qiuyu Wang, Vishal P. Sharma, Hong Shen, Yuanyuan Xiao, Qi Zhu, Xuelian Xiong, Liang Guo, Lin Jiang, Kunimasa Ohta, Siming Li, Haifei Shi, Liangyou Rui, Jiandie D. Lin

Research output: Contribution to journalArticlepeer-review

52 Citations (Scopus)


Thermogenesis is an important contributor to whole-body energy expenditure and metabolic homeostasis. Although circulating factors that promote energy expenditure are known, endocrine molecules that suppress energy expenditure have remained largely elusive. Here we found that Tsukushi (TSK) is a liver-enriched secreted factor that is highly inducible in response to increased energy expenditure. Hepatic Tsk expression and plasma TSK levels were elevated in obesity. In mice, TSK deficiency increased sympathetic innervation and norepinephrine release in adipose tissue, leading to enhanced adrenergic signalling and thermogenesis, attenuation of brown fat whitening, and protection from diet-induced obesity. Our data reveal TSK as part of a negative feedback mechanism that gates thermogenic energy expenditure and highlights TSK as a potential target for therapeutic intervention in metabolic disease.

Original languageEnglish
Pages (from-to)251-260
Number of pages10
JournalNature Metabolism
Issue number2
Publication statusPublished - Feb 1 2019
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Physiology (medical)
  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Cell Biology


Dive into the research topics of 'The hepatokine Tsukushi gates energy expenditure via brown fat sympathetic innervation'. Together they form a unique fingerprint.

Cite this