@article{e4e4c5a5bff6480caf12809b851be61f,
title = "The immune checkpoint B7-H3 (CD276) regulates adipocyte progenitor metabolism and obesity development",
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.",
author = "Elodie Picarda and Galbo, {Phillip M.} and Haihong Zong and Rajan, {Meenu Rohini} and Ville Wallenius and Deyou Zheng and Emma B{\"o}rgeson and Rajat Singh and Jeffrey Pessin and Xingxing Zang",
note = "Funding Information: We thank K. Hofmeyer, L. Scandiuzzi, and J. Chinai for breeding mice and early work; E. Tarabra and M. Aoun for technical assistance with tissue respirometry; R. Gupta for providing Ing-svf cells; and A. Briceno for technical assistance on the Leica SP8 confocal microscope; and the Flow Cytometry Core Facility and Analytical Imaging Facility. Funding: the Flow Cytometry Core Facility and Analytical Imaging Facility is partially supported through NCI Cancer Center Support grant P30CA013330. This work used a high-speed/resolution P250 whole slide scanner and the Leica SP8 confocal microscope that were purchased with funding from National Institutes of Health SIG grants 1S10OD019961-01 and 1S10OD023591-01, respectively. E.B. is supported by ERC grant StG #804418, the Wallenberg Centre for Molecular and Translational Medicine at University of Gothenburg and Knut and Alice Wallenberg Foundation, the Swedish Research Council (#2016/82), and SSMF (#S150086). This study was supported by National Institutes of Health grants R01DK100525 (X.Z.) and P30DK020541 (Einstein-Mount Sinai Diabetes Research Center). Author contributions: Conceptualization: E.P., R.S., J.P., and X.Z. Formal analysis: P.M.G.J. and D.Z. Investigation: E.P., H.Z., and M.R.R. Resources: E.B. and V.W. Writing—Original draft: E.P. Writing—Review and editing: E.P., P.M.G.J., H.Z., M.R.R., D.Z., E.B., R.S., J.P., and X.Z. Visualization: E.P. Funding acquisition and supervision: X.Z. Competing interests: The authors declare that they have no competing interests. Data and materials availability: All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials. Publisher Copyright: Copyright {\textcopyright} 2022 The Authors, some rights reserved;",
year = "2022",
month = apr,
doi = "10.1126/sciadv.abm7012",
language = "English (US)",
volume = "8",
journal = "Science advances",
issn = "2375-2548",
publisher = "American Association for the Advancement of Science",
number = "17",
}
