Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 490, Issue 2, Pages 247-252Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2017.06.031
Keywords
Glucagon-like peptide-1 amide (GLP-1); Gastric inhibitory polypeptide (GIP); Pro-opiomelanocortin (POMC); Intracerebroventricluar (ICV); Obesity
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Funding
- Research Resettlement Fund for the new faculty of Seoul National University
- Cooperative Research Program of Basic Medical Science and Clinical Science from Seoul National University College of Medicine [800-20150083]
- Basic Science Research Program through the National Research Foundation of Korea (NRF) -Ministry of Education [NRF-2014R1A1A2059013]
- National Research Foundation of Korea grant - Korea government (MSIP) [2010-0028631]
- Brain Korea 21 Program by the Korea
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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. (C) 2017 The Authors. Published by Elsevier Inc.
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