Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Am J Physiol Cell Physiol. 2013 Jun 15;304(12):C1141-9. doi: 10.1152/ajpcell.00351.2012. Epub 2013 Jan 30.
Adipose tissue is a heterogeneous organ with remarkable variations in fat cell metabolism depending on the anatomical location. However, the pattern and distribution of bioactive lipid mediators between different fat depots and their relationships in complex diseases have not been investigated. Using LC-MS/MS-based metabolo-lipidomics, here we report that human subcutaneous (SC) adipose tissues possess a range of specialized proresolving mediators (SPM) including resolvin (Rv) D1, RvD2, protectin (PD) 1, lipoxin (LX) A4, and the monohydroxy biosynthetic pathway markers of RvD1 and PD1 (17-HDHA), RvE1 (18-HEPE), and maresin 1 (14-HDHA). The "classic" eicosanoids prostaglandin (PG) E₂, PGD₂, PGF2α, leukotriene (LT) B₄, 5-hydroxyeicosatetraenoic acid (5-HETE), 12-HETE, and 15-HETE were also identified in SC fat. SC fat from patients with peripheral vascular disease (PVD) exhibited a marked deficit in PD1 and 17-HDHA levels. Compared with SC, perivascular adipose tissue displayed higher SPM levels, suggesting an enhanced resolution capacity in this fat depot. In addition, augmented levels of eicosanoids and SPM were observed in SC fat surrounding foot wounds. Notably, the profile of SC PGF2α differed significantly when patients were grouped by body mass index (BMI). In the case of peri-wound SC fat, BMI negatively correlated with PGE₂. In this tissue, proresolving mediators RvD2 and LXA₄ were identified in lower levels than the proinflammatory LTB₄. Collectively, these findings demonstrate a diverse distribution of bioactive lipid mediators depending on the localization of human fat depots and uncover a specific SPM pattern closely associated with PVD.
脂肪组织是一个异质性器官，其脂肪细胞代谢在不同解剖位置存在显著差异。然而，不同脂肪组织中生物活性脂质介质的分布模式及其在复杂疾病中的关系尚未得到研究。本研究采用基于 LC-MS/MS 的代谢脂质组学方法，报告了人类皮下脂肪组织（SC）中存在一系列特殊的促分解介质（SPM），包括 resolvin（Rv）D1、RvD2、protectin（PD）1、lipoxin（LX）A4 以及 RvD1 和 PD1 的单羟基生物合成途径标志物（17-HDHA）、RvE1（18-HEPE）和maresin 1（14-HDHA）。“经典”类二十烷酸前列腺素（PG）E₂、PGD₂、PGF2α、白三烯（LT）B₄、5-羟基二十碳四烯酸（5-HETE）、12-HETE 和 15-HETE 也在 SC 脂肪中被鉴定出来。与 SC 脂肪相比，周围血管疾病（PVD）患者的 SC 脂肪中 PD1 和 17-HDHA 水平显著降低。与 SC 相比，血管周围脂肪组织显示出更高的 SPM 水平，这表明该脂肪组织具有增强的分解能力。此外，在足部伤口周围的 SC 脂肪中观察到更多的类二十烷酸和 SPM 水平。值得注意的是，根据体重指数（BMI）对 SC 脂肪 PGF2α 进行分组时，PGF2α 的分布明显不同。在伤口周围的 SC 脂肪中，PGF2α 与 BMI 呈负相关。在该组织中，与促炎 LTB₄ 相比，RvD2 和 LXA₄ 的含量较低。总之，这些发现表明，生物活性脂质介质的分布取决于人类脂肪组织的定位，揭示了一种与 PVD 密切相关的特殊 SPM 模式。
