Department of Biomedicine, Faculty of Medicine, University of Porto, Portugal.
Department of Clinical Haematology, Centro Hospitalar of Porto, Portugal.
Int J Med Sci. 2017 Jul 19;14(9):853-861. doi: 10.7150/ijms.19638. eCollection 2017.
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.
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。
