Abstract
Abstract
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.