The immune checkpoint B7-H3 (CD276) regulates adipocyte progenitor metabolism and obesity development.
Sci Adv
; 8(17): eabm7012, 2022 Apr 29.
Article
in En
| MEDLINE
| ID: mdl-35476450
ABSTRACT
The immune checkpoint B7-H3 (CD276) is a member of the B7 family that has been studied in the tumor microenvironment and immunotherapy, but its potential role in metabolism remains largely unknown. Here, we show that B7-H3 is highly expressed in mouse and human adipose tissue at steady state, with the highest levels in adipocyte progenitor cells. B7-H3 is rapidly down-regulated upon the initiation of adipocyte differentiation. Combined RNA sequencing and metabolic studies reveal that B7-H3 stimulates glycolytic and mitochondrial activity of adipocyte progenitors. Loss of B7-H3 in progenitors results in impaired oxidative metabolism program and increased lipid accumulation in derived adipocytes. Consistent with these observations, mice knocked out for B7-H3 develop spontaneous obesity, metabolic dysfunction, and adipose tissue inflammation. Our results reveal an unexpected metabolic role for B7-H3 in adipose tissue and open potential new avenues for the treatment of metabolic diseases by targeting the B7-H3 pathway.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
Sci Adv
Year:
2022
Document type:
Article
Affiliation country:
United States