The immune checkpoint B7-H3 (CD276) regulates adipocyte progenitor metabolism and obesity development

• DOI: 10.1126/sciadv.abm7012
• Publication Date: 2022-04-27T17:58:00Z
• Authors: Elodie Picarda; Phillip M. Galbo; Haihong Zong; Meenu Rohini Rajan; Ville Wallenius; Deyou Zheng; Emma Börgeson; Rajat Singh; Jeffrey Pessin; Xingxing Zang
• Keywords: 0303 health sciences; 03 medical and health sciences; Biomedicine and Life Sciences; 3. Good health

The immune checkpoint B7-H3 (CD276) is a member of the B7 family that has been studied in tumor microenvironment and immunotherapy, but its potential role metabolism remains largely unknown. Here, we show highly expressed mouse human adipose tissue at steady state, with highest levels adipocyte progenitor cells. rapidly down-regulated upon initiation differentiation. Combined RNA sequencing metabolic studies reveal stimulates glycolytic mitochondrial activity progenitors. Loss progenitors results impaired oxidative program increased lipid accumulation derived adipocytes. Consistent these observations, mice knocked out for develop spontaneous obesity, dysfunction, inflammation. Our an unexpected open new avenues treatment diseases by targeting pathway.