First Author | Picarda E | Year | 2022 |
Journal | Sci Adv | Volume | 8 |
Issue | 17 | Pages | eabm7012 |
PubMed ID | 35476450 | Mgi Jnum | J:338555 |
Mgi Id | MGI:7275877 | Doi | 10.1126/sciadv.abm7012 |
Citation | Picarda E, et al. (2022) The immune checkpoint B7-H3 (CD276) regulates adipocyte progenitor metabolism and obesity development. Sci Adv 8(17):eabm7012 |
abstractText | 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. |