Irisin mediates beiging of adipose-derived mesenchymal stem cells through binding to TRPC3

• Published in: BMC biology 2022-05, Vol.20 (1), p.95-95, Article 95
• Main Authors: Xue, Chunling, Li, Xuechun, Ba, Li, Shen, Yamei, Sun, Zhao, Gu, Junjie, Yang, Ying, Han, Qin, Zhao, Robert Chunhua
• Format: Article
• Language: English
• Subjects: Adipocytes; Adipose Tissue, White - metabolism; Adipose tissues; AKT protein; Amino acids; Animals; Beiging; Bioenergetics; Body fat; Body temperature; Body weight; Brain; Calcium; Calcium - metabolism; Calcium influx; Cardiomyocytes; Cell differentiation; Cell metabolism; Chemical energy; Diabetes; Energy Metabolism; Excitatory amino acids; Fibronectins; Health aspects; IRISIN; Kinases; Mammals; Mass spectrometry; Medical research; Medicine, Experimental; Membrane proteins; Mesenchymal Stem Cells; Metabolic disorders; Mice; Muscles; Norepinephrine; Obesity; Peptide hormones; Peroxisome proliferator-activated receptors; Phosphorylation; Physiological aspects; PPAR gamma - genetics; PPAR gamma - metabolism; Proteins; Scientific imaging; Skeletal muscle; Smooth muscle; Stem cell transplantation; Stem cells; T cell receptors; TRPC Cation Channels; TRPC3
• ISSN: 1741-7007; 1741-7007
• DOI: 10.1186/s12915-022-01287-2

Beiging of white fat plays an important role in energy metabolism. Beige adipocytes contribute to the regulation of body weight and body temperature through expenditure of chemical energy to produce heat, and they have therefore recently attracted considerable attention as potential targets for therapeutic approaches in metabolic disorders, including obesity. All adipocytes, including beige adipocytes, differentiate from mesenchymal stem cells (MSCs), which may provide an important path for clinical intervention; however, the mechanism of beiging of human adipose cell-derived MSCs is not fully understood. Here, we provide insights on the role of IRISIN, which is known to be secreted by skeletal muscle and promote beiging of white fat. We established an IRISIN-induced mesenchymal stem cell beiging model and found that IRISIN protein interacts with the MSC membrane protein TRPC3. This interaction results in calcium influx and consequential activation of Erk and Akt signaling pathways, which causes phosphorylation of PPARγ. The phosphorylated PPARγ enters the nucleus and binds the UCP1 promoter region. Furthermore, the role of TRPC3 in the beiging of MSCs was largely abolished in Trpc3 mice. We additionally demonstrate that the calcium concentration in the brain of mice increases upon IRISIN stimulation, followed by an increase in the content of excitatory amino acids and norepinephrine, while Trpc3 mice exhibit the reverse effect. We found that TRPC3 is a key factor in irisin-induced beiging of MSCs, which may provide a new target pathway in addressing metabolic disorders. Our results additionally suggest that the interaction of irisin with TRPC3 may affect multiple tissues, including the brain.