Hildebrand, S.; Retiet, M.; Pregler, B. E. F.; Graelmann, F. J.; Loeffler, S.; Foerster, I.; Pfeifer, A.

Background/Objectives: The adipose tissue endothelium plays a critical role for tissue function in acting as an interface between circulating blood and the various tissue-resident cells. Proper endothelial function ensures, among other things, well-regulated adipose tissue lipid in- and efflux, immune cell diapedesis, and oxygen supply. Dysregulated lipid flux, inflammation, and adipose tissue hypoxia are hallmarks of adipose tissue dysfunction and metaflammation. Additionally, lipid uptake and oxygen supply are important processes enabling heat production in active brown adipose tissue (BAT), which is associated with cardiometabolic health in humans. However, so far, little is known about the role of adipose tissue endothelial cells (ECs) and their intercellular communication with other adipose tissue cell compartments. Particularly, how this communication changes during thermogenic stimuli such as cold exposure is largely unknown. Methods: We used transcriptome analysis of adipose tissue ECs to identify EC Cxcl12 as a potential regulator of adipose tissue function. In vitro experiments were performed on primary sympathetic neurons and immortalized ECs. The role of EC Cxcl12 in adipose tissue function was analyzed in vivo using conditional knock-out mice. Results: Cxcl12 expression was induced in BAT ECs upon exposure to cold. Recombinant CXCL12 increased axon outgrowth in primary sympathetic neurons and angiogenesis in ECs. Conditional knock-out of Cxcl12 in ECs did not yield a discernable phenotype in mice either in normal housing or during cold adaption. Additionally, we could show that EC-derived CXCL12 does not play a role in adipose tissue dysfunction during obesity. Conclusions: Cxcl12 is highly expressed in the adipose tissue endothelium, but appears to be dispensable for adipose tissue function.