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

• Published in: Scientific reports 2018-07, Vol.8 (1), p.10644-9, Article 10644
• Main Authors: Kimura, Tomohiko, Obata, Atsushi, Shimoda, Masashi, Shimizu, Ikki, da Silva Xavier, Gabriela, Okauchi, Seizo, Hirukawa, Hidenori, Kohara, Kenji, Mune, Tomoatsu, Moriuchi, Saeko, Hiraoka, Arudo, Tamura, Kentaro, Chikazawa, Genta, Ishida, Atsuhisa, Yoshitaka, Hidenori, Rutter, Guy A., Kaku, Kohei, Kaneto, Hideaki
• Format: Article
• Language: English
• Subjects: 13; 13/1; 13/51; 13/89; 14; 14/63; 38; 38/39; 692/163; 692/163/2743/393; Aged; Aged, 80 and over; Animals; Arteries; Arteries - cytology; Arteries - pathology; Arteries - surgery; Arteriosclerosis; Blood pressure; Body Mass Index; Cyclin-dependent kinases; Down-Regulation; Endothelium, Vascular - cytology; Endothelium, Vascular - pathology; Endothelium, Vascular - surgery; Female; Gene expression; Glucagon-Like Peptide-1 Receptor - genetics; Glucagon-Like Peptide-1 Receptor - metabolism; Human subjects; Human Umbilical Vein Endothelial Cells; Humanities and Social Sciences; Humans; Male; Middle Aged; multidisciplinary; Obesity; Obesity - pathology; RNA, Small Interfering - metabolism; Science; Science (multidisciplinary); Short term; siRNA; Transcription Factor 7-Like 2 Protein - genetics; Transcription Factor 7-Like 2 Protein - metabolism; Tunica Intima - cytology; Tunica Intima - pathology; Tunica Intima - surgery; Tunica Media - cytology; Tunica Media - pathology; Tunica Media - surgery
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-018-28849-1

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.