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, subeffective 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.