Human epicardial fat has a beige profile and contains higher type 2 innate lymphoid cells than subcutaneous fat

IF 4.2 2区医学 Q1 ENDOCRINOLOGY & METABOLISM

Obesity Pub Date : 2024-05-15 DOI:10.1002/oby.24023

Elisa Doukbi, Patricia Ancel, Anne Dutour, Astrid Soghomonian, Shaista Ahmed, Victoria Castejon, Christelle Piperoglou, Vlad Gariboldi, Marien Lenoir, Eric Lechevallier, Bastien Gondran-Tellier, Romain Boissier, Mikael Ebbo, Frédéric Vély, Bénédicte Gaborit

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Abstract

Objective

Epicardial adipose tissue (EAT) is a visceral fat that has been associated with coronary artery disease and atrial fibrillation. Previous work has revealed that EAT exhibits beige features.

Methods

First, a new pan-genomic microarray analysis was performed on previously collected paired human EAT and thoracic subcutaneous AT (thSAT) from the EPICAR study (n = 31) to decipher a specific immune signature and its link with browning genes. Then, adaptive (T and B cells) and innate lymphoid cell (ILC1, ILC2, and ILC3) immunophenotyping assay panels, including CD127, CD117, and prostaglandin D2 receptor 2, were performed on prospectively collected paired human multiorgan donors (n = 18; INTERFACE study).

Results

In the EPICAR study, a positive correlation between the T helper cell subtype Th2 immune pathway and browning genes was found in EAT versus thSAT (r = 0.82; p < 0.0001). In the INTERFACE study, this correlation was also observed (r = 0.31; p = 0.017), and a preponderance of CD4⁺T cells, CD8⁺T cells, and a few B cells was observed in all ATs (p < 0.0001). An increase in ILCs was observed in visceral AT (VAT) (i.e., EAT + VAT; 30 ± 5 ILCs per gram of AT) compared with subcutaneous counterparts (i.e., thSAT + abdominal SAT; 8 ± 2 ILCs per gram of AT; p = 0.001), with ILC1 being the most frequent (ILC1 > ILC3 > ILC2). Numbers of ILCs per gram of AT correlated with several Th2 or browning genes (IL-13, TNF receptor superfamily member 9 [TNFRSF9], and alkaline phosphatase, biomineralization associated [ALPL]). Interestingly, a specific increase in EAT-ILC2 compared with other ATs was observed, including a significant proportion expressing CD69 and/or CD25 activation markers (97.9% ± 1.2%; p < 0.0001). Finally, more natural killer cells were observed in EAT + VAT than in thSAT + abdominal SAT (p = 0.01). Exclusion of patients with coronary artery disease in the EPICAR and INTERFACE studies did not modify the main findings. Gene expression phenotyping confirmed specific upregulation of Th2 pathway and browning genes (IL-33 and uncoupling protein 1 [UCP-1]) in EAT.

Conclusions

This is the first study, to our knowledge, to provide a comparison between innate and adaptive lymphoid cells in human EAT. Further studies are ongoing to decipher whether these cells could be involved in EAT beiging.

Abstract Image

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人体心外膜脂肪呈米黄色，比皮下脂肪含有更多的 2 型先天性淋巴细胞。

目的：心外膜脂肪组织（EAT心外膜脂肪组织（EAT）是一种内脏脂肪，与冠心病和心房颤动有关。以往的研究表明，心外膜脂肪组织具有米色特征：方法：首先，对以前从 EPICAR 研究（n = 31）中收集的成对人体 EAT 和胸腔皮下 AT（thSAT）进行了新的泛基因组微阵列分析，以破译特定的免疫特征及其与褐变基因的联系。然后，对前瞻性收集的配对人类多器官供体（n = 18；INTERFACE 研究）进行适应性（T 细胞和 B 细胞）和先天性淋巴细胞（ILC1、ILC2 和 ILC3）免疫分型检测，包括 CD127、CD117 和前列腺素 D2 受体 2：结果：在 EPICAR 研究中发现，EAT 与 thSAT 中的 T 辅助细胞亚型 Th2 免疫途径与褐变基因之间呈正相关（r = 0.82；p +T 细胞、CD8+T 细胞和少量 B 细胞在所有 AT 中均可观察到（p ILC3 > ILC2）。每克 AT 的 ILC 数量与几个 Th2 或褐变基因（IL-13、TNF 受体超家族成员 9 [TNFRSF9] 和碱性磷酸酶、生物矿化相关 [APL]）相关。有趣的是，与其他AT相比，EAT-ILC2出现了特异性增加，包括表达CD69和/或CD25活化标记的显著比例（97.9%±1.2%；P 结论：这是我们的首次研究：据我们所知，这是第一项对人类 EAT 中先天性和适应性淋巴细胞进行比较的研究。目前正在进行进一步研究，以确定这些细胞是否参与了 EAT 的形成。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Obesity 医学-内分泌学与代谢

CiteScore

11.70

自引率

1.40%

发文量

261

审稿时长

2-4 weeks

期刊介绍： Obesity is the official journal of The Obesity Society and is the premier source of information for increasing knowledge, fostering translational research from basic to population science, and promoting better treatment for people with obesity. Obesity publishes important peer-reviewed research and cutting-edge reviews, commentaries, and public health and medical developments.