Specific loss of adipocyte CD248 improves metabolic health via reduced white adipose tissue hypoxia, fibrosis and inflammation

脂肪细胞 CD248 的特定缺失可通过减少白色脂肪组织缺氧、纤维化和炎症来改善代谢健康

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作者:Paul Petrus, Tara L Fernandez, Michelle M Kwon, Jenny L Huang, Victor Lei, Nooshin Seyed Safikhan, Subashini Karunakaran, Daniel J O'Shannessy, Xiaowei Zheng, Sergiu-Bogdan Catrina, Earl Albone, Jukka Laine, Kirsi Virtanen, Susanne M Clee, Timothy J Kieffer, Christophe Noll, André C Carpentier, Jame

Background

A positive energy balance promotes white adipose tissue (WAT) expansion which is characterized by activation of a repertoire of events including hypoxia, inflammation and extracellular matrix remodelling. The transmembrane glycoprotein CD248 has been implicated in all these processes in different malignant and inflammatory diseases but its potential impact in WAT and metabolic disease has not been explored.

Methods

The role of CD248 in adipocyte function and glucose metabolism was evaluated by omics analyses in human WAT, gene knockdowns in human in vitro differentiated adipocytes and by adipocyte-specific and inducible Cd248 gene knockout studies in mice. Findings: CD248 is upregulated in white but not brown adipose tissue of obese and insulin-resistant individuals. Gene ontology analyses showed that CD248 expression associated positively with pro-inflammatory/pro-fibrotic pathways. By combining data from several human cohorts with gene knockdown experiments in human adipocytes, our

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