The Anti-Obesity Effect of D-Lys3- GHRP-6 Peptide, GHSR Receptor Antagonist in Rats

Neuropeptide Y (NPY) neurons express growth hormone secretagogues receptor (GHSR-Ia). Fasting or ghrelin increases food intake by stimulating NPY gene expression via GHSR-Ia. D-Lys3 -GHRP-6، a ghrelin receptor antagonist، decreases food intakes and body weight. The present study aimed to investigate the molecular mechanism of the anorexigenic effect of D-Lys3 -GHRP-6 in food deprived rats. Fifteen food deprived rats (3 groups) received central injections of saline or D-Lys3 -GHRP-6 (2 or 20nmol) respectively and mean food intake was measured at one hour after injections. Mean plasma ghrelin concentration was measured by RIA، and NPY gene expression was determined by semi quantitative RT-PCR in the hypothalamus. Fifteen rats in three groups، received central injection of saline or initiations and on the D-Lys3 -GHRP-6 (2 or 20nmol) twice daily for 9 days respectively. Body weight was determined at third، 7th and 10th day of the experiment. Mean plasma ghrelin concentration، mean food intake and NPY gene expression significantly increased in food deprived rats compared to fed animals. D-Lys3 –GHRP-6 (2 nmol) did not significantly change ghrelin، food intake and NPY mRNA levels، compared to the food deprived rats. However D-Lys3 –GHRP-6 (20 nmol) significantly decreased ghrelin، food intake and NPY mRNA level compared to food deprived group. Results showed that D-Lys3 -GHRP-6 may exert its anorexigenic effect on food intake by influencing the expression of peptides involved in the regulation of energy homeostasis، and may be suggested for the treatment of obesity.