Pereira Maria J, Mathioudaki Argyri, Hetty Susanne, Sedigh Amir, Eriksson Jan W, Svensson Maria K
Department of Medical Sciences, Clinical Diabetology and Metabolism, Uppsala University, Uppsala, Sweden.
Department of Surgical Sciences, Transplantation Surgery, Uppsala University, Uppsala, Sweden.
Mol Med. 2025 Jul 22;31(1):262. doi: 10.1186/s10020-025-01323-1.
Alterations in kidney-associated adipose tissue depots, specifically renal sinus (RSAT) and perirenal adipose tissue (PRAT), may contribute to metabolic, cardiovascular, and chronic kidney diseases. We compared transcriptomic profiles and phenotypes, including adipocyte size, glucose uptake, and insulin action in RSAT and PRAT from healthy individuals.
Subcutaneous (SAT), omental (OAT) and renal adipose tissue biopsies were collected from healthy kidney donors (20 women, 20 men; BMI 20 to 36 kg/m). Adipocyte size and basal and insulin-stimulated glucose uptake rate were measured in isolated adipocytes. Transcriptomic profiling and immune cell composition estimates (RNA seq, n = 30), were performed to evaluate differences between PRAT and RSAT, with OAT as a benchmark.
PRAT exhibited significantly larger adipocytes and higher insulin-stimulated glucose uptake than RSAT. Of 1113 significantly differentially expressed genes (DEGs) (PRAT: 571 down- and 542 upregulated), thermogenic and metabolic genes (UCP1, CIDEA, and CKMT1B) were enriched in PRAT, while inflammation-related genes (NFKBIA, BIRC3, and IRF1) in RSAT. Pathway analysis indicated activation of metabolic pathways (TCA cycle and oxidative phosphorylation), in PRAT, which contrasts with the immune and inflammatory pathways in RSAT and OAT. Immune cell gene signatures revealed an anti-inflammatory environment in PRAT (eosinophils and activated NK cells), and a pro-inflammatory profile in RSAT (M0 macrophages). Immunohistochemistry confirmed higher CD68- and IL1B-positive cells in RSAT than in PRAT. When overweight individuals were compared to lean, genes related to the VEGF signaling were upregulated in PRAT and Ras signaling in RSAT. Additionally, metabolic pathways linked to the TCA cycle as well as carbon and fatty acid metabolism were downregulated.
The different kidney-associated adipose tissue depots exhibit distinct gene expression and functional profiles. PRAT displays higher expression of thermogenic markers and less inflammatory profile compared to RSAT and also OAT. In contrast, RSAT exhibits an inflammatory and macrophage-enriched profile, more closely resembling OAT. This study highlights the heterogeneity of the kidney-associated adipose tissue depots and could suggest that an excessive amount of RSAT may impact development of metabolic, cardiovascular, and chronic kidney diseases.
肾脏相关脂肪组织库的改变，特别是肾窦脂肪组织（RSAT）和肾周脂肪组织（PRAT），可能与代谢性疾病、心血管疾病和慢性肾脏病有关。我们比较了健康个体RSAT和PRAT的转录组谱及表型，包括脂肪细胞大小、葡萄糖摄取和胰岛素作用。
从健康肾脏供体（20名女性，20名男性；BMI 20至36kg/m²）获取皮下脂肪组织（SAT）、网膜脂肪组织（OAT）和肾周脂肪组织活检样本。测量分离脂肪细胞中的脂肪细胞大小以及基础和胰岛素刺激的葡萄糖摄取率。进行转录组分析和免疫细胞组成评估（RNA测序，n = 30），以OAT为基准评估PRAT和RSAT之间的差异。
PRAT的脂肪细胞明显大于RSAT，且胰岛素刺激的葡萄糖摄取更高。在1113个显著差异表达基因（DEG）中（PRAT：571个下调和542个上调），产热和代谢基因（UCP1、CIDEA和CKMT1B）在PRAT中富集，而炎症相关基因（NFKBIA、BIRC3和IRF1）在RSAT中富集。通路分析表明PRAT中代谢通路（三羧酸循环和氧化磷酸化）被激活，这与RSAT和OAT中的免疫和炎症通路形成对比。免疫细胞基因特征显示PRAT中存在抗炎环境（嗜酸性粒细胞和活化的自然杀伤细胞），而RSAT中存在促炎特征（M0巨噬细胞）。免疫组织化学证实RSAT中CD68和IL1B阳性细胞高于PRAT。将超重个体与瘦个体进行比较时，PRAT中与血管内皮生长因子信号相关的基因上调，RSAT中与Ras信号相关的基因上调。此外，与三羧酸循环以及碳和脂肪酸代谢相关的代谢通路下调。
不同的肾脏相关脂肪组织库表现出不同的基因表达和功能谱。与RSAT以及OAT相比，PRAT显示出更高的产热标志物表达和更低的炎症特征。相反，RSAT表现出炎症和巨噬细胞富集的特征，更类似于OAT。本研究突出了肾脏相关脂肪组织库的异质性，并可能提示过量的RSAT可能影响代谢性疾病、心血管疾病和慢性肾脏病的发展。
