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Histamine stimulates thermogenesis of brown and beige fat

FENG Yue-Yao¹, ZHANG Yu-Jie², CHANG Yong-Sheng^1,*

¹Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin 300070, China；²National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China

Abstract

β3-adrenergic agonists induce adaptive thermogenesis and promote beiging of white fat. However, it remains unclear which metabolites mediate the stimulatory effects of β3-adrenergic agonists on thermogenesis of brown and beige fat. In this study, adipose tissue was isolated from 8-week-old C57/BL6J male mice by intraperitoneal administration of β3-adrenergic agonist CL316,243 for RNA-Seq, which revealed that histidine decarboxylase, a key enzyme in histamine synthesis, was strongly induced in adipose by CL316,243. Therefore, we speculated that histamine might be involved in the process of thermogenesis in adipose tissue. We determined the physiological role and mechanism by which histamine promotes fat thermogenesis by intravenous administering histamine to C57BL/6J mice fed a normal or a high-fat diet. The results showed that intravenous injection of histamine into C57BL/6J mice fed a normal diet stimulated the expression of thermogenic genes, including peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) and uncoupling protein 1 (UCP1), in brown adipose tissue (BAT) and inguinal white adipose tissue (iWAT). H&E staining also suggested that histamine treatment decreased the size of lipid droplets in adipocytes. Moreover, histamine treatment also enhanced thermogenesis of fat in high-fat diet induced obese mice, and improved glucose intolerance and fatty liver phenotype. Finally, we demonstrated that the effects of histamine on the thermogenic program were cell autonomous. Our data suggest that histamine may mediate the effects of β3-adrenergic agonists on thermogenesis of fat.

Key words: Histamine; thermogenesis; obesity; UCP1; PGC-1α

Received: 2020-11-25　　Accepted: 2021-02-26

Corresponding author: 常永生　　E-mail: changys@tmu.edu.cn

DOI: 10.13294/j.aps.2021.0039

Citing This Article：

FENG Yue-Yao, ZHANG Yu-Jie, CHANG Yong-Sheng. Histamine stimulates thermogenesis of brown and beige fat. Acta Physiol Sin 2021; 73 (5): 821-827 (in Chinese with English abstract).