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人脂肪组织中的肥大细胞:与病态肥胖、炎症状态和糖尿病的联系。

Mast cells in human adipose tissue: link with morbid obesity, inflammatory status, and diabetes.

机构信息

Institut National de la Santé et de la Recherche Médicale Unité 872, Nutriomique, and Université Pierre et Marie Curie-Paris 6, Centre de Recherche des Cordeliers, Unité Mixte de Recherche (UMR) S872, F-75006 Paris, France.

出版信息

J Clin Endocrinol Metab. 2012 Sep;97(9):E1677-85. doi: 10.1210/jc.2012-1532. Epub 2012 Jun 28.

DOI:10.1210/jc.2012-1532
PMID:22745246
Abstract

AIMS AND HYPOTHESIS

Mast cells are immune cells known for their role in several inflammatory and fibrotic diseases. Recent works in mice suggest that mast cells could be cellular actors involved in the pathophysiology of obesity, a disease characterized by white adipose tissue (WAT) and systemic inflammation. The aim of the study was to better characterize mast cells in WAT of obese with or without type 2 diabetes and lean subjects as well as to explore the relationship with WAT inflammation and fibrosis.

METHODS

Subcutaneous and omental adipose tissue from six lean subjects, 10 obese nondiabetic, and 10 diabetic patients was analyzed by immunohistochemistry and real-time PCR for inflammatory and fibrosis markers. Cytokines secretion of mast cells isolated from WAT and cultured in different conditions was estimated by cytokine array kit.

RESULTS

We found that mast cells are activated in human adipose tissue and localized preferentially in fibrosis depots, a local condition that stimulates their inflammatory state. Mast cells with tryptase(+) chymase(+) staining tended to be higher in obese omental adipose tissue. We found positive links between mast cell number and several characteristics of obese WAT including fibrosis, macrophage accumulation, and endothelial cell inflammation. Mast cell number and their inflammatory phenotype are associated with diabetes parameters.

CONCLUSION AND INTERPRETATION

Mast cells are cellular actors of WAT inflammation and possibly fibrotic state found in obesity and diabetes. Whether mast cells could be involved in the pathophysiology of diabetes needs additional study as well as the positioning of these cells in driving pathological alterations of WAT in these chronic metabolic diseases.

摘要

目的和假设

肥大细胞是免疫细胞,其在几种炎症和纤维化疾病中发挥作用。最近在小鼠中的研究表明,肥大细胞可能是参与肥胖症病理生理学的细胞因子,肥胖症的特征是白色脂肪组织(WAT)和全身炎症。本研究的目的是更好地描述肥胖症(伴或不伴 2 型糖尿病)和瘦受试者的 WAT 中的肥大细胞,并探讨与 WAT 炎症和纤维化的关系。

方法

通过免疫组织化学和实时 PCR 分析来自 6 名瘦受试者、10 名肥胖非糖尿病患者和 10 名糖尿病患者的皮下和网膜脂肪组织中炎症和纤维化标志物。通过细胞因子数组试剂盒评估从 WAT 分离并在不同条件下培养的肥大细胞的细胞因子分泌。

结果

我们发现肥大细胞在人类脂肪组织中被激活,并且优先定位于纤维化病灶中,这是一种刺激其炎症状态的局部条件。肥大细胞的类胰蛋白酶(+)糜蛋白酶(+)染色在肥胖的网膜脂肪组织中倾向于更高。我们发现肥大细胞数量与肥胖 WAT 的几个特征之间存在正相关,包括纤维化、巨噬细胞积累和内皮细胞炎症。肥大细胞数量及其炎症表型与糖尿病参数相关。

结论和解释

肥大细胞是肥胖症和糖尿病中发现的 WAT 炎症和可能纤维化状态的细胞因子。肥大细胞是否可能参与糖尿病的病理生理学需要进一步研究,以及这些细胞在这些慢性代谢性疾病中驱动 WAT 病理性改变的定位。

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