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Orexin-induced food intake involves neuropeptide Y pathway
1Department of Pharmacology, Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan.
Abstract:
Orexins (orexin-A and -B) are recently identified neuropeptides, which are thought to be implicated in the regulation of feeding behavior. We used a NPY-Y1 receptor specific antagonist, BIBO3304, to examine whether NPY is involved in orexin-induced feeding behavior. Intracerebroventricular administration of orexin-A (10 nmol) induced food intake in rats (food intake for 3 h; vehicle 0.3+/-0.2 g vs. orexin-A 10 nmol, 4.0+/-0.5 g, n=4). Orexin-induced feeding behavior was partially inhibited by prior administration of BIBO3304 (3 h food intake: orexin-A 10 nmol, 4.0+/-0.5 g vs. BIBO3304 (60 microgram) + orexin-A 10 nmol, 2.2+/-0.2 g, n=4). A low dose of BIBO3304 (30 microgram) did not show a significant inhibitory effect. BIBO3457, an inactive enantiomer, used as a negative control, did not show any inhibitory effect on orexin-A-induced feeding behavior. Fos expression was observed in NPY-containing neurons in the arcuate nucleus 1 h after orexin-A (10 nmol) was administered intracerebroventricularly (control 0.3+/-0.08%, orexin-A 10.2+/-0.8%, n=5 rats/group). These observations suggest that NPY is involved in orexin-induced feeding behavior. However, BIBO3304 did not completely abolish the effect of orexin-A. These results suggest that orexin-A elicits feeding behavior partially via the NPY pathway. The NPY system could be the one of downstream pathways by which orexin-A induces feeding behavior. Another pathway may also be involved in orexin-A-induced feeding behavior, because BIBO3304 did not completely abolish orexin-A-induced feeding behavior.
Insights
Orexin-A stimulates feeding behavior, partly through the neuropeptide Y (NPY) pathway. Blocking NPY-Y1 receptors partially reduced orexin-A
Area of Science:
- Neuroscience
- Endocrinology
- Behavioral Science
Background:
- Orexins (orexin-A and -B) are neuropeptides regulating feeding behavior.
- Neuropeptide Y (NPY) is also implicated in appetite control.
Purpose of the Study:
- To investigate the role of NPY in orexin-A-induced feeding behavior.
- To determine if NPY-Y1 receptors mediate orexin-A's effects on appetite.
Main Methods:
- Administered orexin-A intracerebroventricularly to rats to induce feeding.
- Used BIBO3304, a specific NPY-Y1 receptor antagonist, to block NPY signaling.
- Measured food intake and analyzed Fos expression in NPY-containing neurons.
Main Results:
- Orexin-A significantly increased food intake in rats.
- Pre-administration of BIBO3304 partially inhibited orexin-A-induced feeding.
- Fos expression increased in NPY neurons after orexin-A administration, indicating NPY pathway activation.
- A negative control (BIBO3457) did not affect orexin-A's feeding effects.
Conclusions:
- Orexin-A partially mediates feeding behavior via the NPY pathway.
- The NPY system is one of the downstream pathways for orexin-A's appetite regulation.
- Additional pathways likely contribute to orexin-A-induced feeding behavior.