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Orexin – New appetite-boosting peptides found  

[Discovery of a novel peptide using a genomic technology]

Feeding behavior is regulated by many compounds including peptides and proteins; one of the recent topics in this field is the discovery of the appetite-suppressing protein leptin. Very recently, two homologous peptides, which stimulate food consumption, have been isolated and named orexin-A and orexin-B[Cell, 92, 573 (1998)]. The name orexin is from the Greek word [orexis] for appetite. These peptides were discovered in studies carried out to determine the endogenous ligands to the orphan receptor OX1R and OX2R; the notable sequence similarity of these receptors lies in the sequence of the Y₂ neuropeptide Y (NPY) receptor.

Orexin-A is a 33-residue peptide with two intramolecular disulfide linkages, while orexin-B is a linear 28-residue peptide. The mutual sequence similarity is high, especially in their C-terminal regions. Human, rat and mouse peptide sequences have been determined and the primary structure of orexin-A is completely conserved among these species including bovine. When orexin-A and B are administered into the lateral hypothalamus (the brain’s “feeding center”), food intake was stimulated in a dose-dependent manner (3/30 nmol) for a few hours with slight duration difference. In addition, hypothalamic orexin mRNA is found to be up-regulated in fasting. Orexin-A and B are coded tandemly in the same mRNA flanked by the double basic amino acid residues.

The same mRNA was isolated by another group from rat hypothalamic mRNA clone; the putative reading frames corresponding to orexin-A and B are named hypocretin based on the sequence similarity to secretin. [Proc. Natl. Acad. Sci., 95, 322 (1998)]

Newly discovered appetite-boosting peptides orexin-A and B may be useful tools to analyze the regulation mechanism of feeding behavior.

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