Intracerebroventricular (ICV) injections of glucose‐dependent insulinotropic polypeptide in rats on hypothalamic gene expression by real time RT‐PCR

Abstract

Glucose-dependent insulinotropic polypeptide (GIP), a peptide synthesized and secreted from the small intestine, is a major incretin factor of the enteroinsular axis and linked to dietary-induced obesity. The objective of this study was to investigate effects of central GIP administration on hypothalamic gene expression profiles in rats. Brains were collected from male rats following intracerebroventricular (ICV) injections with 10 μl artificial cerebrospinal fluid (aCSF) or 10 μg GIP daily for 4 days. Hypothalami were dissected and total RNA was extracted and reverse transcribed, then real time reverse transcription polymerase chain reaction (RT-PCR) was performed to determine mRNA expression of a series of hypothalamic biomarkers. RT-PCR results showed that central GIP treatment significantly upregulated mRNA levels of hypothalamic CART, NPY, AVP, CCK, CREB1, GABRD, GNRH1, HCRT, MAPK1, OXT, TH, TNF, TRH, and SCT. GIP did not alter the mRNA levels of hypothalamic STAT3, SOCS3, GHRH and POMC2. There were significant positive correlations between CCK and GABRD (r=.91, p<.001), CREB1 and MAPK1 (r=.87, p<.001), CREB1 and CCK (r=.89, p<.001), and MAPK1 and CCK (r=.78, p<.001). This hypothalamic gene profile suggests that GIP may be involved in feeding, stress, and anxiety-related behaviors and that MAPK signaling might be an important pathway in GIP-induced activities. This study suggests how central GIP may affect hypothalamic gene expression in rats, and thus may add to understanding hypothalamic involvement in GIP influenced activities.