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In this study, we discovered novel ghrelin sensitivity\u2010enhancing peptides. Ghrelin sensitivity was evaluated by examining whether dipeptide samples enhanced the calcium response to ghrelin in the growth hormone secretagogue receptor\u2010transfected cell line. First, dipeptides were screened using a 336\u2010dipeptide library and we revealed that Ser\u2010Tyr (SY) potentiated ghrelin sensitivity in particular. Based on the structure\u2010activity relationship determined using the dipeptide library and comprehensive analysis of peptides in the chymotrypsin digest of soy \u03b2\u2010conglycinin (\u03b2\u2010CG), which enhanced ghrelin sensitivity, candidate peptides were narrowed down. Among the chemosynthesized peptides, we discovered that an undecapeptide, SLVNNDDRDSY, corresponding to \u03b2\u2010CG\u03b1(267\u2010277), stimulated ghrelin sensitivity\n                    <jats:italic>in vitro<\/jats:italic>\n                    . This peptide enhanced the orexigenic activity of ghrelin in C57BL\/6 mice and stimulated food intake. Thus, we demonstrated that SLVNNDDRDSY stimulated ghrelin sensitivity\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    and named it \u201csoy\u2010\n                    <jats:italic>f<\/jats:italic>\n                    ortelin\u201d. Moreover, orally administered soy\u2010\n                    <jats:italic>f<\/jats:italic>\n                    ortelin had a similar but smaller effect in the young C57BL\/6 mice, whereas it strongly stimulated food intake in 2\u2010year\u2010old aged mice that exhibited high blood ghrelin levels and low ghrelin sensitivity. In conclusion, we discovered soy\u2010\n                    <jats:italic>f<\/jats:italic>\n                    ortelin as a novel peptide that enhances ghrelin sensitivity\n                    <jats:italic>in vivo<\/jats:italic>\n                    and\n                    <jats:italic>in vitro<\/jats:italic>\n                    and increases food intake in young and aged ghrelin\u2010resistant mice. Soy\u2010\n                    <jats:italic>f<\/jats:italic>\n                    ortelin is the first food\u2010derived peptide reported to enhance ghrelin sensitivity.\n                  <\/jats:p>","DOI":"10.1096\/fj.202201482r","type":"journal-article","created":{"date-parts":[[2023,3,1]],"date-time":"2023-03-01T10:51:00Z","timestamp":1677667860000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Soy\u2010\n                    <i>f<\/i>\n                    ortelin: A ghrelin sensitivity\u2010enhancing peptide that stimulates food intake in aged mice"],"prefix":"10.1096","volume":"37","author":[{"given":"Ken","family":"Shimizu","sequence":"first","affiliation":[{"name":"Division of Food Science and Biotechnology, Graduate School of Agriculture Kyoto University  Kyoto 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