Proinflammatory and lipid biomarkers mediate metabolically healthy obesity: A proteomics study.
Proinflammatory and lipid biomarkers mediate metabolically healthy obesity: A proteomics study.
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DOI：
10.1002/oby.21482
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发表时间：
2016-06
期刊：
影响因子：
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通讯作者：
Adeyemo A
中科院分区：
文献类型：
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作者：
Doumatey AP;Zhou J;Zhou M;Prieto D;Rotimi CN;Adeyemo A
代谢健康肥胖（MHO）表型是一种重要的肥胖亚型，其中肥胖不伴有任何代谢合并症。然而，潜在的分子机制仍然难以捉摸。在本研究中，使用鸟枪法蛋白质组学方法来识别与 MHO 相关的循环生物分子和通路。受试者为 20 名非裔美国女性：10 名 MHO 病例和 10 名代谢异常肥胖 (MAO) 对照者。使用无标记蛋白质组学检测和定量血清蛋白。分析两组之间蛋白质的差异表达，并分析差异表达蛋白质列表以确定富集的生物学途径。 MHO 和对照之间有 20 种蛋白质有差异表达。这些蛋白质包括：血红蛋白亚基（HBA1，P = 6.00 × 10−18），触珠蛋白相关蛋白（HPR，P = 1.2 × 10−15），载脂蛋白（APOB-100，P = 1.50 × 10−40；APOA4，P = 1.1 × 10−14)、视黄醇结合蛋白 4 (RBP4，P = 7.1 × 10−08) 和 CRP (P = 2.0 × 10−04)。与 MAO 相比，MHO 与较低水平的促炎生物标志物和较高水平的抗炎生物标志物相关。通路分析显示脂质和炎症通路的富集，包括 LXR/RXR 和 FXR/RXR 激活以及急性期反应信号传导。这些发现表明，防止炎症和脂质过程失调是 MHO 的主要分子标志。本研究中确定的候选生物标志物（AHSG、RBP4 和 APOA4）是 MHO 的潜在预后标志物。
The metabolically healthy obesity (MHO) phenotype is an important obesity subtype in which obesity is not accompanied by any metabolic comorbidity. However, the underlying molecular mechanisms remain elusive. In this study, a shotgun proteomics approach to identify circulating biomolecules and pathways associated with MHO was used. The subjects were 20 African‐American women: 10 MHO cases and 10 metabolically abnormal individuals with obesity (MAO) controls. Serum proteins were detected and quantified using label‐free proteomics. Differential expression of proteins between the two groups was analyzed, and the list of differentially expressed proteins was analyzed to determine enriched biological pathways. Twenty proteins were differentially expressed between MHO and controls. These proteins included: hemoglobin subunits (HBA1, P = 6.00 × 10−18), haptoglobin‐related protein (HPR, P = 1.2 × 10−15), apolipoproteins (APOB‐100, P = 1.50 × 10−40; APOA4, P = 1.1 × 10−14), retinol‐binding protein 4 (RBP4, P = 7.1 × 10−08), and CRP (P = 2.0 × 10−04). MHO was associated with lower levels of proinflammatory and higher levels of anti‐inflammatory biomarkers when compared with MAO. Pathway analysis showed enrichment of lipids and inflammatory pathways, including LXR/RXR and FXR/RXR activation, and acute phase response signaling. These findings suggested that protection from dysregulated inflammatory and lipid processes were primary molecular hallmarks of MHO. The candidate biomarkers (AHSG, RBP4, and APOA4) identified in this study are potential prognostic markers for MHO.