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

Elodie Picarda; Phillip M. Galbo; Haihong Zong; Meenu Rohini Rajan; Ville Wallenius; Deyou Zheng; Emma Börgeson; Rajat Singh; Jeffrey Pessin; Xingxing Zang

doi:10.1126/sciadv.abm7012

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

Elodie Picarda, Phillip M. Galbo, Haihong Zong, Meenu Rohini Rajan, Ville Wallenius, Deyou Zheng, Emma Börgeson, Rajat Singh, Jeffrey Pessin, Xingxing Zang

Research output: Contribution to journal › Article › peer-review

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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.

Original language	English (US)
Article number	eabm7012
Journal	Science Advances
Volume	8
Issue number	17
DOIs	https://doi.org/10.1126/sciadv.abm7012
State	Published - Apr 2022

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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.",

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AU - Wallenius, Ville

AU - Zheng, Deyou

AU - Börgeson, Emma

AU - Singh, Rajat

AU - Pessin, Jeffrey

AU - Zang, Xingxing

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

Abstract

ASJC Scopus subject areas

UN SDGs

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