Central administration of GLP-1 and GIP decreases feeding in mice

作者：NamKoong Cherl; Kim Min Sun; Jang Byeong Tak; Lee Young Hee; Cho Young Mm; Choi Hyung Jin^*

来源：Biochemical and Biophysical Research Communications, 2017, 490(2): 247-252.

DOI：10.1016/j.bbrc.2017.06.031

• Glucagon-like peptide-1 amide (GLP-1)
• Gastric inhibitory polypeptide (GIP)
• Pro-opiomelanocortin (POMC)
• Intracerebroventricluar (ICV)
• Obesity

Glucagon-like peptide-1 amide (GLP-1) and gastric inhibitory polypeptide (GIP) are incretin hormones regulating energy metabolism. GLP-1 and GIP combination is suggested as a promising therapeutic strategy for treatment of obesity and diabetes. However, the neuronal mechanisms are not yet investigated. In the present study, we investigated the role of central GLP-1 and GIP in regulation of body weight homeostasis. The effect of GLP-1 with GIP on food intake, body weight, locomotor activity were determined following intracerebroventricular (ICV) administration of GLP-1 and/or GIP in mice. ICV administration of low dose GLP-1 (0.3 nmol) and GIP (1 and 3 nmol) did not change food intake. However, ICV administration of higher doses GLP-1 (1 and 3 nmol) and GIP (6 nmol) significantly decreased food intake and body weight. To investigate the synergic effect of ICV GLP-1 and GIP, sub effective dose GLP-1 (0.3 nmol) and subeffective dose GIP (1 nmol) were chosen for further co-administration study. ICV co-administration of GLP-1 and GIP significantly decreased food intake, body weight and drinking. ICV co-administration of GLP-1 and GIP significantly increased neuronal activation and pro-opiomelanocortin (POMC) expression in hypothalamic arcuate nucleus. The neuronal activation and POMC expression were observed in two distinct neuronal populations. These results provide neuronal mechanisms supporting the development of GLP-1 and GIP combination therapeutics for treatment of obesity and diabetes.

• 出版日期2017-8-19