| Autor: |
Tian Su, Yue He, Yan Huang, Mingsheng Ye, Qi Guo, Ye Xiao, Guangping Cai, Linyun Chen, Changjun Li, Haiyan Zhou, Xianghang Luo |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
Nature Communications, Vol 15, Iss 1, Pp 1-18 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2041-1723 |
| DOI: |
10.1038/s41467-023-43787-x |
| Popis: |
Abstract The crosstalk between the bone and adipose tissue is known to orchestrate metabolic homeostasis, but the underlying mechanisms are largely unknown. Herein, we find that GCA + (grancalcin) immune cells accumulate in the bone marrow and release a considerable amount of GCA into circulation during obesity. Genetic deletion of Gca in myeloid cells attenuates metabolic dysfunction in obese male mice, whereas injection of recombinant GCA into male mice causes adipose tissue inflammation and insulin resistance. Mechanistically, we found that GCA binds to the Prohibitin-2 (PHB2) receptor on adipocytes and activates the innate and adaptive immune response of adipocytes via the PAK1-NF-κB signaling pathway, thus provoking the infiltration of inflammatory immune cells. Moreover, we show that GCA-neutralizing antibodies improve adipose tissue inflammation and insulin sensitivity in obese male mice. Together, these observations define a mechanism whereby bone marrow factor GCA initiates adipose tissue inflammation and insulin resistance, showing that GCA could be a potential target to treat metainflammation. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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Full text from SpringerLink