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

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.

• Authors: Tomohiko Kimura, Atsushi Obata, Masashi Shimoda, Ikki Shimizu, Gabriela da Silva Xavier, Seizo Okauchi, Hidenori Hirukawa, Kenji Kohara, Tomoatsu Mune, Saeko Moriuchi, Arudo Hiraoka, Kentaro Tamura, Genta Chikazawa, Atsuhisa Ishida, Hidenori Yoshitaka, Guy A Rutter, Kohei Kaku, Hideaki Kaneto
• Journal: Scientific reports (Sci Rep) Vol. 8 Issue 1 Pg. 10644 (Jul 13 2018) ISSN: 2045-2322 [Electronic] England
• PMID: 30006590 (Publication Type: Journal Article)

Chemical References

• GLP1R protein, human
• Glucagon-Like Peptide-1 Receptor
• RNA, Small Interfering
• TCF7L2 protein, human
• Transcription Factor 7-Like 2 Protein

Topics

• Aged
• Aged, 80 and over
• Animals
• Arteries (cytology, pathology, surgery)
• Body Mass Index
• Down-Regulation
• Endothelium, Vascular (cytology, pathology, surgery)
• Female
• Glucagon-Like Peptide-1 Receptor (genetics, metabolism)
• Human Umbilical Vein Endothelial Cells
• Humans
• Male
• Middle Aged
• Obesity (pathology)
• RNA, Small Interfering (metabolism)
• Transcription Factor 7-Like 2 Protein (genetics, metabolism)
• Tunica Intima (cytology, pathology, surgery)
• Tunica Media (cytology, pathology, surgery)