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β肾上腺素受体在外周血单核细胞中表达下调,与中心性肥胖患者更好的代谢特征相关。

β Adrenoceptors are underexpressed in peripheral blood mononuclear cells and associated with a better metabolic profile in central obesity.

机构信息

Department of Biomedicine, Faculty of Medicine, University of Porto, Portugal.

Department of Clinical Haematology, Centro Hospitalar of Porto, Portugal.

出版信息

Int J Med Sci. 2017 Jul 19;14(9):853-861. doi: 10.7150/ijms.19638. eCollection 2017.

Abstract

Central obesity (CO) is an inflammatory disease. Because immune cells and adipocytes are catecholamines(CA)-producing cells, we studied the expression of adrenoceptors (AR) in peripheral blood mononuclear cells (PBMCs) hypothesizing a distinct adrenergic pattern in inflammatory obesity. AR expression was assessed in blood donors categorized by waist circumference (WC) (CO: WC≥0.80 m in women and ≥0.94 m in men). Following a pilot study for all AR subtypes, we measured βAR expression in fifty-seven individuals and correlated this result with anthropometric, metabolic and inflammatory parameters. A ratio (R) between AR mRNA of CO and non-CO<0.5 was considered under and >2.0 over expression. The pilot study revealed no differences between groups, except for βAR mRNA. CO individuals showed underexpression of βAR relatively to those without CO (R=0.08; p=0.009). βAR expression inversely correlated with triacylglycerol (r=-0.271; p=0.041), very low-density lipoprotein-cholesterol (r=-0.313; p=0.018) and leptin (r=-0.392; p=0.012) and positively with high-density lipoprotein-cholesterol (r=0.310: p=0.045) plasma levels. Multiple logistic regression analysis showed a protective effect of βAR expression (≥2x10-6) [odds ratio (OR) 0.177 with respective confidence interval of 95% (95% CI) (0.040- 0.796)] for the occurrence of CO. A higher association was found for women as compared to men (Ξ9:1) [OR 8.972 (95% CI) (1.679-47.949)]. PBMCs βAR, underexpressed in centrally obese, are associated with a better metabolic profile and showed a protective role for the development of CO. The discovery of βAR as a new molecular marker of obesity subphenotypes in PBMCs might contribute to clarify the adrenergic immunomodulation of inflammatory obesity.

摘要

中心性肥胖(CO)是一种炎症性疾病。由于免疫细胞和脂肪细胞是儿茶酚胺(CA)产生细胞,我们研究了外周血单核细胞(PBMC)中肾上腺素能受体(AR)的表达,假设在炎症性肥胖中存在独特的肾上腺素能模式。我们根据腰围(WC)将血液供体分为 CO(女性 WC≥0.80m,男性 WC≥0.94m)和非 CO 组,评估了 AR 表达。在对所有 AR 亚型进行初步研究后,我们在 57 名个体中测量了βAR 表达,并将此结果与人体测量、代谢和炎症参数相关联。CO 和非 CO 之间 AR mRNA 比值(R)<0.5 被认为是低表达,>2.0 被认为是高表达。初步研究表明,除了βAR mRNA 外,两组之间没有差异。与非 CO 个体相比,CO 个体的βAR 表达较低(R=0.08;p=0.009)。βAR 表达与三酰甘油(r=-0.271;p=0.041)、极低密度脂蛋白胆固醇(r=-0.313;p=0.018)和瘦素(r=-0.392;p=0.012)呈负相关,与高密度脂蛋白胆固醇(r=0.310;p=0.045)呈正相关。多元逻辑回归分析显示,βAR 表达(≥2x10-6)[比值比(OR)0.177,相应的 95%置信区间(95%CI)(0.040-0.796)]对 CO 的发生具有保护作用。与男性相比,女性的相关性更高(Ξ9:1)[OR 8.972(95%CI)(1.679-47.949)]。中心性肥胖的 PBMC 中βAR 表达下调,与更好的代谢特征相关,并对 CO 的发生具有保护作用。在 PBMC 中发现βAR 作为肥胖亚表型的新分子标志物,可能有助于阐明炎症性肥胖的肾上腺素能免疫调节。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2781/5562192/6f9486b659a0/ijmsv14p0853g001.jpg

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