Instituto Pluridisciplinar and Facultad de Farmacia, Universidad Complutense de Madrid, 28040 Madrid, Spain.
Department of Clinical Pharmacology and Toxicology, Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany.
Int J Mol Sci. 2023 Nov 30;24(23):17008. doi: 10.3390/ijms242317008.
Perirenal adipose tissue (PRAT) surrounding the kidney is emerging as a player and novel independent risk factor in diabetic kidney disease (DKD); DKD is a complication of diabetes and is a major cause of increased cardiovascular (CV) risk and CV mortality in affected patients. We determined the effect of diabetes induction on (i) kidney and CV damage and (ii) on the expression of proinflammatory and profibrotic factors in both the PRAT and the mesenteric adipose tissue (MAT) of Munich Wistar Frömter (MWF) rats. The 16-week-old male MWF rats (n = 10 rats/group) were fed standard chow (MWF-C) or a high-fat/high-sucrose diet for 6 weeks together with low-dose streptozotocin (15 mg/kg i.p.) at the start of dietary exposure (MWF-D). Phenotyping was performed at the end of treatment through determining water intake, urine excretion, and oral glucose tolerance; use of the homeostatic model assessment-insulin resistance index (HOMA-IR) evidenced the development of overt diabetes manifestation in MWF-D rats. The kidney damage markers and were significantly higher in MWF-D rats, as were the amounts of PRAT and MAT. A diabetes-induced upregulation in , , , and was observed in both the PRAT and the MAT. was increased in the PRAT but not in the MAT of MWF-D, whereas was lower and higher in the PRAT and the MAT, respectively. Urinary albumin excretion and blood pressure were not further increased by diabetes induction, while heart weight was higher in the MWF-D. In conclusion, our results show a proinflammatory and profibrotic in vivo environment in PRAT induced by diabetes which might be associated with kidney damage progression in the MWF strain.
肾周脂肪组织(PRAT)环绕在肾脏周围,它作为一个参与者和新的独立危险因素出现在糖尿病肾病(DKD)中;DKD 是糖尿病的一种并发症,也是受影响患者心血管(CV)风险增加和 CV 死亡率增加的主要原因。我们确定了糖尿病诱导对(i)肾脏和 CV 损伤以及(ii)慕尼黑 Wistar Frömter(MWF)大鼠的 PRAT 和肠系膜脂肪组织(MAT)中促炎和促纤维化因子表达的影响。16 周龄雄性 MWF 大鼠(n = 10 只/组)给予标准饲料(MWF-C)或高脂肪/高蔗糖饮食 6 周,并在饮食暴露开始时给予低剂量链脲佐菌素(15mg/kg ip)(MWF-D)。通过测定水摄入量、尿量和口服葡萄糖耐量来进行治疗结束时的表型分析;使用稳态模型评估-胰岛素抵抗指数(HOMA-IR)证明了 MWF-D 大鼠出现明显的糖尿病表现。MWF-D 大鼠的肾脏损伤标志物和明显升高,PRAT 和 MAT 的量也增加。在 PRAT 和 MAT 中观察到糖尿病诱导的 、 、 和 上调。在 PRAT 中 增加,但在 MAT 中不增加,而 分别在 PRAT 和 MAT 中降低和增加。糖尿病诱导并未进一步增加尿白蛋白排泄和血压,而 MWF-D 大鼠的心脏重量更高。总之,我们的结果表明,糖尿病诱导的 PRAT 中存在促炎和促纤维化的体内环境,这可能与 MWF 大鼠肾脏损伤进展有关。