The effect of the orexins on food intake: comparison with neuropeptide Y, melanin-concentrating hormone and galanin

Mar 17, 1999The Journal of endocrinology

How orexins influence eating compared to other appetite-related brain chemicals

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Abstract

Orexin-A significantly stimulated food intake by 2.2±0.4 g compared to saline at 3 nmol.

Orexin-B's effect on food intake was inconsistent, showing stimulation only on some occasions.
Both orexins stimulated food intake significantly less than neuropeptide Y (NPY), which had a greater effect.
Orexin-A and orexin-B stimulated food intake similarly to melanin-concentrating hormone (MCH) but less than NPY.
Intracerebroventricular injection of orexin-A resulted in high expression of c-fos, indicating neuronal activation in key hypothalamic regions.
Intra-paraventricular nucleus injection of orexin-A increased food intake by one gram compared to saline.

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Orexin-A and orexin-B (the hypocretins) are recently described neuropeptides suggested to have a physiological role in the regulation of food intake in the rat. We compared the orexigenic effect of the orexins administered intracerebroventricular (ICV) with other known stimulants of food intake, one strong, neuropeptide Y (NPY), and two weaker, melanin-concentrating hormone (MCH) and galanin. Orexin-A consistently stimulated food intake, but orexin-B only on occasions. Both peptides stimulated food intake significantly less than NPY, but to a similar extent to MCH (2 h food intake: NPY 3 nmol, 7.2+/-0.9 g vs saline, 1.5+/-0.2 g, P<0.001, MCH 3 nmol, 3.2+/-0.8 g vs saline, P<0.01, orexin-B 30 nmol, 2. 6+/-0.5 g vs saline, P=0.11) and to galanin (1 h food intake: galanin 3 nmol, 2.0+/-0.4 g vs saline, 0.8+/-0.2 g, P<0.05, orexin-A 3 nmol 2.2+/-0.4 g vs saline, P<0.01; 2 hour food intake: orexin-B 3 nmol, 2.4+/-0.3 g vs saline, 1.3+/-0.2 g, P<0.05). Following ICV orexin-A, hypothalamic c-fos, a maker of neuronal activation, was highly expressed in the paraventricular nucleus (PVN), and the arcuate nucleus (P<0.005 for both). IntraPVN injection of orexin-A stimulated 2 h food intake by one gram (orexin-A 0.03 nmol, 1.6+/-0. 3 g vs saline, 0.5+/-0.3 g, P<0.005). These findings support the suggestion that the orexins stimulate food intake. However, this effect is weak and may cast doubt upon their physiological importance in appetite regulation in the rat.

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The effect of the orexins on food intake: comparison with neuropeptide Y, melanin-concentrating hormone and galanin

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