GIP-Dependent Expression of Hypothalamic Genes

Abstract

GIP (glucose dependent insulinotrophic polypeptide), originally identified as an incretin peptide synthesized in the gut, has recently been identified, along with its receptors (GIPR), in the brain. Our objective was to investigate the role of GIP in hypothalamic gene expression of biomarkers linked to regulating energy balance and feeding behavior related neurocircuitry. Rats with lateral cerebroventricular cannulas were administered 10 mu g GIP or 10 mu l artificial cerebrospinal fluid (SF) daily for 4 days, after which whole hypothalami were collected. Real time Taqrnan (TM) RT-PCR was used to quantitatively compare the mRNA expression levels of a set of genes in the hypothalamus. Administration of GIP resulted in up-regulation of hypothalamic mRNA levels of AVP (46.9 +/- 4.5 %), CART (25.9 +/- 2.7 %), CREB1 (38.5 +/- 4.5 %), GABRD (67.1 +/- 11 %), JAK2 (22.1 +/- 3.6 %), MAPK1 (33.8 +/- 7.8 %), NPY (25.3 +/- 5.3 %), OXT (49.1 +/- 5.1 %), STAT3 (21.6 +/- 3.8 %), and TH (33.9 +/- 8.5 %). In a second experiment the same set of genes was evaluated in GIPR(-/-) and GIPR(+/?) mice to determine the effect of lack of GIP stimulation on gene expression. In GIPR(-/-) mice expressions of the following genes were down-regulated: AVP (27.1 +/- 7.5 %), CART (28.3 +/- 3.7 %), OXT (25.2 +/- 5.8 %), PTGES (23.9 +/- 4.5 %), and STAT3 (8.8 +/- 2.3 %). These results suggest that AVP, CART, OXT and STAT3 may be involved in energy balance-related hypothalamic circuits affected by GIP.