#492 Depot-specific metabolic and thermogenic profiles in perirenal and renal sinus adipose tissue

Abstract Background and Aims Kidney-associated adipose tissue depots, i.e., renal sinus (RSAT) and perirenal adipose tissue (PRAT), may contribute to metabolic, cardiovascular and chronic kidney diseases linked to obesity. The aim of this study was to characterize PRAT compared to RSAT and omental adipose tissue (OAT) by adipocyte size, glucose uptake, transcriptomics and immune cell fractions in healthy individuals. Method Adipose tissue biopsies were collected from healthy kidney donors (20 female, 20 male). Adipocyte glucose uptake and size were measured in isolated adipocytes. Transcriptomic profiling and immune cell composition estimates (RNA seq data), were performed to evaluate differences between PRAT and RSAT, using OAT as a benchmark. Results PRAT exhibited significantly larger adipocytes and higher insulin-stimulated glucose uptake than RSAT. 1113 significant differentially expressed genes (DEGs) were identified (PRAT: 571 down- and 542 upregulated) with enrichment of thermogenic and metabolic genes (UCP1, CIDEA, and CKMT1B) in PRAT and inflammation-related genes (NFKBIA, BIRC3, and IRF1) in RSAT. Pathway analysis highlighted activation of metabolic processes, including the TCA cycle and oxidative phosphorylation in PRAT contrasting to immune and inflammatory pathways in RSAT and OAT (see Fig. 1A–D). Immune cells gene signatures the depots: PRAT displayed an anti-inflammatory environment with transcripts associated with eosinophils and activated NK cells, whereas RSAT exhibited a pro-inflammatory profile associated with M0 macrophages. Conclusion Kidney-associated adipose tissue depots PRAT and RSAT exhibit distinct profiles. PRAT shows thermogenic and anti-inflammatory characteristics suggesting a protective metabolic role. RSAT inflammatory profile, more closely resembling OAT, may impact metabolic, cardiovascular and chronic kidney diseases. These findings highlight the heterogeneity of kidney-associated adipose tissue depots.