#4362 A DISTINCT TRANSCRIPTOME SIGNATURE IN HUMAN RENAL SINUS ADIPOSE TISSUE – A POTENTIAL IMPORTANCE FOR RENAL DYSFUNCTION?

Abstract

Abstract Background and Aims Previous studies have suggested that the anatomical location and function of adipose tissue (AT) is of relevance for normal as well as impaired renal function. Renal sinus AT (RSAT) is a perivascular fat compartment located around the renal arteries. The aim of this study was to perform a transcriptomic characterization of RS in comparison with omental (OAT) and subcutaneous (SAT) AT in healthy individuals. Method 30 kidney donors (15 men (50%), age 50 ± 11 years, BMI 25.8 ± 2.9 kg/m2, eGFR 83 ± 9 mL/min/1.73 m2, HOMA-IR 2.5 ± 1.1) were included in the study. RS, OAT and SAT biopsies were performed during laparoscopic unilateral nephrectomy. RNA-sequencing analyses and untargeted transcriptomics were performed. Analysis of differentially expressed genes (DEG) was employed to discover quantitative changes in expression levels between two tissue depots (RSAT) vs OAT and SAT, respectively. Gene Ontology (GO) term enrichment was used to summarize the function of genes that were differentially expressed. Results Paired samples of renal sinus fat (RSAT) to be compared with omental (OAT) or subcutaneous adipose tissue (SAT) were available in 26 and 22 subjects, respectively. Out of 12210 genes characterised in these AT depots, 463 genes (3,7%) were uniquely expressed in RS when compared to both OAT and SAT (co-expression Venn-diagram in figure 1). In addition, DEG analyses showed that 1639 genes had higher, whereas 384 had lower, expression in RS than in OAT. For RSAT versus SAT the corresponding numbers were 3789 and 2534, respectively. Among the gene that were differentially regulated, the following pathways were most significantly enhanced in RSAT compared to OAT or SAT (figure 2): chemotaxis and cell migration (e.g. cell and leukocyte chemotaxis and leukocyte migration), and immune response (e.g. T-cell activation, immune response-activating signal transduction, adaptive immune response). Conversely, ATP synthesis (e.g. oxidative phosphorylation, cellular respiration, mitochondrial complex) and extracellular matrix pathways were significantly attenuated in RS compared to SAT and OAT, respectively (not shown). A targeted analysis of specific gene markers that have previously been reported to be associated with chronic kidney disease (CKD) showed that AT expression of pro-inflammatory factors such as visfatin, IL-6, IL-11, IL-1β and IL-18 were higher in RSAT vs SAT or OAT (not shown). In addition, the expression of some genes, differently regulated in RSAT, and known to associated with progression of CKD, e.g. Fc Gamma Receptor IIa (FCGR2A), NF-kappa-B inhibitor beta (NFKBIB), Nuclear Factor, Erythroid 2 (NFE2) and Oncostatin M (OSM), were positively correlated with BMI (data not shown). Conclusion This study in healthy kidney donors indicates that the transcriptome signature of renal sinus AT seems to be distinct from subcutaneous and omental AT. Gene ontology analyses pointed towards an inflammatory environment and lower mitochondrial function in the renal sinus compared to other adipose tissue depots. These findings are likely to define depot-specific AT functions that may be of importance for renal function and disease.