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肥胖人群血管 GLP-1 受体表达下调。

Down-regulation of vascular GLP-1 receptor expression in human subjects with obesity.

机构信息

Division of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki, Japan.

Department of Diabetes, Sakakibara Heart Institute, Okayama, Japan.

出版信息

Sci Rep. 2018 Jul 13;8(1):10644. doi: 10.1038/s41598-018-28849-1.

DOI:10.1038/s41598-018-28849-1
PMID:30006590
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6045606/
Abstract

It has been thought that incretin signaling prevents arteriosclerosis, and very recently anti-arteriosclerotic effects through GLP-1 receptor were finally demonstrated in clinical human study. The purpose of this study was to investigate how vascular GLP-1 receptor expression is influenced in human subjects. First, we evaluated GLP-1 receptor expression in human arteries in immunostaining. Next, we separated the artery into the intima and media, and evaluated gene expression levels of various factors. We divided the subjects into obesity and non-obesity group and compared their expression levels between them. Finally, we evaluated which factors determine vascular GLP-1 receptor expression. GLP-1 receptor expression in intima and media was lower in obesity group compared to non-obesity group which was correlated with the alteration of TCF7L2 expression. Multiple regression analyses showed that BMI was an independent determining factor for GLP-1 receptor expression in the intima and media. Furthermore, using small interfering RNA method and TCF7L2-EGFP adenovirus, we showed that TCF7L2 was involved in GLP-1 receptor expression in human vascular cells. Taken together, vascular GLP-1 receptor and TCF7L2 expression was significantly down-regulated in human subjects with obesity. In addition, it is likely that TCF7L2 functions as a modulator of vascular GLP-1 receptor expression.

摘要

人们一直认为肠促胰岛素信号可以预防动脉粥样硬化，最近在临床人体研究中终于证明了 GLP-1 受体的抗动脉粥样硬化作用。本研究旨在探讨血管 GLP-1 受体在人体中的表达如何受到影响。首先，我们通过免疫染色评估了人类动脉中的 GLP-1 受体表达。接下来，我们将动脉分为内膜和中膜，并评估了各种因素的基因表达水平。我们将受试者分为肥胖组和非肥胖组，并比较了它们之间的表达水平。最后，我们评估了哪些因素决定了血管 GLP-1 受体的表达。与非肥胖组相比，肥胖组的内膜和中膜 GLP-1 受体表达较低，这与 TCF7L2 表达的改变有关。多元回归分析表明，BMI 是内膜和中膜 GLP-1 受体表达的独立决定因素。此外，通过小干扰 RNA 方法和 TCF7L2-EGFP 腺病毒，我们表明 TCF7L2 参与了人类血管细胞中 GLP-1 受体的表达。综上所述，肥胖人群的血管 GLP-1 受体和 TCF7L2 表达明显下调。此外，TCF7L2 可能作为血管 GLP-1 受体表达的调节剂发挥作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0632/6045606/0026c75f4d54/41598_2018_28849_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0632/6045606/52dcee14c796/41598_2018_28849_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0632/6045606/fcaf956f8099/41598_2018_28849_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0632/6045606/f6659b4f2ed5/41598_2018_28849_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0632/6045606/0026c75f4d54/41598_2018_28849_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0632/6045606/52dcee14c796/41598_2018_28849_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0632/6045606/fcaf956f8099/41598_2018_28849_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0632/6045606/f6659b4f2ed5/41598_2018_28849_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0632/6045606/0026c75f4d54/41598_2018_28849_Fig4_HTML.jpg

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