Orexin-mediated feeding behavior involves both leptin-sensitive and -insensitive pathways.
Orexin-A and -B are neuropeptides that are implicated in the regulation of vigilance states and energy homeostasis. Orexins are specifically produced by neurons located within the lateral hypothalamic area (LHA), a region implicated in the regulation of feeding behavior. Here, we examined the functional interactions between orexins and anorectic factors [leptin, alpha-melanocyte-stimulating hormone (alpha-MSH) and glucagon-like peptide-1 (GLP-1)] in rats. Intracerebroventricular injection of orexin-A (10 nmol) potently augmented food intake in rats. Neuropeptide Y (NPY) (0.3 nmol) and galanin (3 nmol) also induced a transient increase in food intake. Both NPY- and galanin-induced feeding behaviors were completely inhibited by preadministration of leptin (3 microg), while the same or a higher dose (10 microg) of leptin only partially inhibited orexin-A or -B-induced increase of food intake. Preadministration of anorectic peptides (alpha-MSH and GLP-1), which are shown to be regulated by leptin, abolished NPY-induced feeding; however, orexin-induced feeding was only partially inhibited by these anorectic peptides. These observations suggest that NPY- and galanin-induced increases of feeding involve a leptin-sensitive pathway, while orexin-induced feeding involves both leptin-sensitive and -insensitive pathways.
Zhu
Y
Y
Department of Pharmacology, Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
Yamanaka
A
A
Kunii
K
K
Tsujino
N
N
Goto
K
K
Sakurai
T
T
D000818:Animals; D002352:Carrier Proteins / Q000494:pharmacology*; D005247:Feeding Behavior / Q000187:drug effects*; D019004:Galanin / Q000494:pharmacology; D005934:Glucagon / Q000494:pharmacology; D052216:Glucagon-Like Peptide 1; D007276:Injections, Intraventricular; D047908:Intracellular Signaling Peptides and Proteins; D020738:Leptin / Q000494:pharmacology*; D008297:Male; D009479:Neuropeptides / Q000494:pharmacology*; D064446:Orexin Receptors; D000068797:Orexins; D010446:Peptide Fragments / Q000494:pharmacology; D011498:Protein Precursors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors; D000521:alpha-MSH / Q000494:pharmacology
D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D020738:Leptin; D009479:Neuropeptides; D064446:Orexin Receptors; D000068797:Orexins; D010446:Peptide Fragments; D011498:Protein Precursors; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide; D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor; D000521:alpha-MSH; D019004:Galanin; D052216:Glucagon-Like Peptide 1; D005934:Glucagon