In rats, the appetite‑boosting peptide GHRP‑6 reliably increased food intake, while orexin (another appetite peptide) only sparked eating when the stress‑hormone CRF was blocked. This shows that orexin’s effect on hunger is tangled with CRF and NPY signals, making its impact less straightforward.

Orexin (hypocretin) is a peptide that has been found to stimulate food intake in rats. However, we have recently demonstrated that orexin stimulates the release of corticotropin releasing hormone (CRF) which has been known to decrease the food intake. Therefore, we examined the mechanism of effect of orexin on food intake. Although the other appetite stimulating peptides; neuropeptide Y (NPY), agouti-related peptide (AGRP) and one of the growth hormone releasing secretagogue (GHRP-6) stimulated dose-dependently the food intake during 2 h in the early light period, orexin did not increase significantly the food intake. No significant increase was also observed during 2 h in the early dark period. However, pretreatment with alpha-helical CRF, an antagonist of CRF, or anti-CRF antiserum resulted in significant increase of food intake by orexin. Orexin-stimulated feeding under these conditions was blocked by NPY Y1 receptor antagonist (1229U91). In an 8 h-fasting rat, anti-orexin serum decreased slightly the food intake. These results suggest that effect of orexin on the food intake may be complex because of orexin-CRF and orexin-NPY linkage.