Atherosclerosis and Metabolism Unit, Katholieke Universiteit Leuven, Herestraat 49, PB 705, 3000 Leuven, Belgium.
J Clin Endocrinol Metab. 2012 Jul;97(7):E1213-8. doi: 10.1210/jc.2012-1008. Epub 2012 Apr 24.
Inflammation during obesity is associated with higher risk of metabolic syndrome and coronary artery disease (CAD). Activation of the inflammatory toll-like receptor (TLR)/nuclear factor κB (NFκB) signaling in monocytes contributes to inflammation. Weight loss after bariatric surgery leads to significant improvement of obesity-related comorbidities. MicroRNA (miR), a class of small noncoding RNA, have been implicated as negative regulators of inflammatory processes.
This study sought to identify dysregulated miR in monocytes of obese patients associated with TLR/NFκB signaling, metabolic syndrome, and CAD.
DESIGN, SETTING, AND PATIENTS: This retrospective study included two independent cohorts of 21 morbidly obese and 125 high-risk obese and nonobese patients in a hospitalized care setting.
INTERVENTION included bariatric surgery (n = 21) with a 3-month follow-up.
miR expressions in CD14(+) monocytes were determined by microarray analysis. TLR/NFκB-related miR were identified by an in silico target prediction analysis. Their expression was validated by quantitative RT-PCR. Their association with metabolic syndrome and angiographically documented CAD was assessed.
miR-181a, -181b, and -181d, identified as possible regulators of the TLR/NFκB signaling, were decreased in obese monocytes, and weight loss normalized their expression to levels observed in monocytes of lean persons. miR-181a but not miR-181b and miR-181d was associated with a higher number of metabolic syndrome components and with CAD even after adjustment for traditional risk factors, obesity and the metabolic syndrome.
This study demonstrates that the TLR/NFκB-related miR-181a is down-regulated in monocytes of obese patients and suggests that it is a putative biomarker of metabolic syndrome and CAD.
肥胖症患者体内的炎症与代谢综合征和冠状动脉疾病（CAD）的发病风险升高有关。单核细胞中炎症性 toll 样受体（TLR）/核因子 κB（NFκB）信号的激活会导致炎症。减重手术后体重减轻可显著改善肥胖相关的合并症。微小 RNA（miRNA）是一类小的非编码 RNA，已被认为是炎症过程的负调控因子。
本研究旨在鉴定与 TLR/NFκB 信号、代谢综合征和 CAD 相关的肥胖患者单核细胞中失调的 miRNA。
设计、地点和患者：本回顾性研究包括两个独立的队列，共纳入了 21 名病态肥胖患者和 125 名高危肥胖患者和非肥胖患者，这些患者均在住院治疗环境中接受治疗。
干预措施包括减重手术（n=21），并在术后 3 个月进行随访。
通过微阵列分析确定 CD14（+）单核细胞中的 miRNA 表达。通过计算机目标预测分析鉴定 TLR/NFκB 相关的 miRNA。通过定量 RT-PCR 验证它们的表达。评估它们与代谢综合征和血管造影证实的 CAD 的相关性。
miR-181a、-181b 和 -181d 被鉴定为可能调节 TLR/NFκB 信号的 miRNA，它们在肥胖患者的单核细胞中表达降低，而体重减轻使它们的表达恢复到瘦人单核细胞中的水平。miR-181a 但不是 miR-181b 和 miR-181d 与更多的代谢综合征成分以及即使在调整了传统危险因素、肥胖和代谢综合征后与 CAD 相关。
本研究表明，肥胖患者单核细胞中的 TLR/NFκB 相关 miRNA-181a 下调，并提示其可能是代谢综合征和 CAD 的潜在生物标志物。
