Biology subjects

Graelmann, F. J.

Publications and source records attributed to Graelmann, F. J..

2 recordsLinked to original sources

bioRxiv2026

Endothelial CXCL12 is dispensable for adipose tissue function

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.

physiology↗

bioRxiv2024

Differential cell type-specific function of the aryl hydrocarbon receptor and its repressor in diet-induced obesity and fibrosis

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor regulating xenobiotic responses as well as physiological metabolism. Dietary AhR ligands activate the AhR signaling axis in the intestine and throughout the organism, whereas AhR activation is negatively regulated by the AhR repressor (AhRR). While AhR-deficient mice are known to be resistant to diet-induced obesity (DIO), we here demonstrate that AhRR deficiency also leads to a robust, but not as profound protection from DIO and hepatosteatosis. Under conditions of DIO, AhRR-/- mice did not accumulate TCA cycle intermediates in the circulation in contrast to wild-type (WT) mice, indicating protection from metabolic dysfunction. This effect could be mimicked by dietary supplementation of AhR ligands in WT mice. Because of the predominant expression of the AhRR in myeloid cells, AhRR-deficient macrophages were analyzed for changes in metabolism and showed major metabolic alterations regarding oxidative phosphorylation and mitochondrial activity as well as increased expression of genes involved in de novo lipogenesis and mitochondrial biogenesis. Mice with a genetic deficiency of the AhRR in myeloid cells did not show alterations in weight gain after high fat diet (HFD) but demonstrated ameliorated liver damage compared to control mice. Further, deficiency of the AhR in myeloid cells also did not affect weight gain but led to enhanced liver damage and adipose tissue fibrosis compared to controls. Although conditional ablation of either the AhR or AhRR in myeloid cells did not recapitulate the phenotype of the global knockout, our findings suggest that enhanced AhR signaling in myeloid cells deficient for AhRR protects from diet-induced liver damage and fibrosis, whereas myeloid cell-specific AhR deficiency is detrimental.

immunology↗