Department of Molecular Medicine and Surgery, Karolinska Institutet, Centre for Molecular Medicine, L8:00 Karolinska University Hospital, 17176 Stockholm, Sweden.
J Intern Med. 2011 Apr;269(4):410-9. doi: 10.1111/j.1365-2796.2010.02293.x. Epub 2010 Nov 5.
Low-grade systemic inflammation, oxidative stress and peripheral insulin resistance are intimately associated and contribute to the increased risk of cardiovascular complications in advanced chronic kidney disease (CKD). Because altered adipose tissue activities have previously been linked to pathophysiological processes in various inflammatory and metabolic diseases we hypothesized that the uraemic milieu in patients with CKD may interact with the adipose tissue, provoking an unfavourable shift in its transcriptional output.
Twenty-one adipokine mRNAs were quantified in abdominal subcutaneous adipose tissue (SAT) biopsies and serum/plasma concentrations of inflammatory markers and related protein products were measured.
The study was conducted at the Karolinska University Hospital, Huddinge, and Karolinska Institutet, Stockholm, Sweden.
Thirty-seven patients with CKD [15 women, median 58 (interquartile range 49-65) years] and nine nonuraemic individuals [four women, age 62 (45-64) years] were recruited prior to initiation of peritoneal dialysis catheter insertion or elective hernia repair/laparoscopic cholecystectomy, respectively.
Even after correction for body mass index, SAT from patients showed a significant upregulation of inflammatory pathway genes interleukin 6 (3.0-fold, P=0.0002) and suppressor of cytokine signalling 3 (2.5-fold, P=0.01), as well as downregulation of leptin (2.0-fold, P=0.03) and the oxidative stress genes uncoupling protein 2 (1.5-fold, P=0.03) and cytochrome b-245, alpha polypeptide (1.5-fold, P=0.005), in relation to controls.
These gene expression differences suggest that inflammatory and oxidative stress activities may be important features of the intrinsic properties of uraemic adipose tissue, which may have significant effects on the uraemic phenotype.
低度系统性炎症、氧化应激和外周胰岛素抵抗密切相关，增加了晚期慢性肾脏病（CKD）患者发生心血管并发症的风险。由于脂肪组织活性的改变与各种炎症和代谢性疾病的病理生理过程有关，我们假设 CKD 患者的尿毒症环境可能与脂肪组织相互作用，促使其转录产物发生不利转变。
在腹部皮下脂肪组织（SAT）活检中定量检测了 21 种脂肪因子 mRNA，测量了炎症标志物和相关蛋白产物的血清/血浆浓度。
该研究在瑞典斯德哥尔摩卡罗林斯卡大学医院和卡罗林斯卡研究所进行。
37 例 CKD 患者（15 名女性，中位年龄 58（四分位距 49-65）岁）和 9 名非尿毒症个体（4 名女性，年龄 62（45-64）岁），分别在开始腹膜透析导管插入术或择期疝修补/腹腔镜胆囊切除术之前入选。
即使校正体重指数后，与对照组相比，患者的 SAT 显示炎症途径基因白细胞介素 6（3.0 倍，P=0.0002）和细胞因子信号转导抑制因子 3（2.5 倍，P=0.01）显著上调，瘦素下调（2.0 倍，P=0.03）和氧化应激基因解偶联蛋白 2（1.5 倍，P=0.03）和细胞色素 b-245，α多肽（1.5 倍，P=0.005）。
这些基因表达差异表明，炎症和氧化应激活性可能是尿毒症脂肪组织固有特性的重要特征，这可能对尿毒症表型有重大影响。
