Wheat‐ghretropins: novel ghrelin‐releasing peptides derived from wheat protein

• Published in: FEBS open bio Vol. 11; no. 4; pp. 1144 - 1152
• Main Authors: Tanikawa, Kana, Kaneko, Kentaro, Abe, Shimon, Nakato, Jyunya, Tokuyama, Yuki, Odaka, Sayano, Iwakura, Hiroshi, Sato, Masaru, Kurabayashi, Atsushi, Suzuki, Hideyuki, Makita, Miki, Ikemoto, Hiroyuki, Matsumura, Shigenobu, Inoue, Kazuo, Ohinata, Kousaku
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.04.2021; John Wiley and Sons Inc; Wiley
• Subjects: Amino Acid Sequence; Animals; Anorexia; Appetite; Cell Line; cell lines; Chromatography; Chromatography, Liquid; Chymotrypsin - chemistry; comprehensive peptide analysis; Enzymes; Experiments; Food; Food intake; Gastric motility; gastrointestinal motility; Ghrelin; Ghrelin - chemistry; Ghrelin - metabolism; Gluten; Glutens - chemistry; Growth hormones; hormone secretion; Hydrolysis; Immunoassay; Liquid chromatography; Mass Spectrometry; Mass spectroscopy; Mice; Mice, Transgenic; Older people; Oral administration; Peptides; Plant Growth Regulators - chemistry; Plant Growth Regulators - metabolism; Proteins; Proteolysis; Quality of life; Scientific imaging; Secretion; Solvents; somatotropin; stomach; Structure-Activity Relationship; structure-activity relationships; Triticum - metabolism; wheat gluten; wheat peptide; wheat protein; United States > US; Japan; comprehensive peptide analysis; ghrelin; wheat peptide; structure-activity relationship; food intake
• ISSN: 2211-5463; 2211-5463
• DOI: 10.1002/2211-5463.13124

Ghrelin is an endogenous orexigenic hormone mainly produced by stomach cells and is reported to influence appetite, gastrointestinal motility and growth hormone secretion. We observed that enzymatic digest of wheat gluten stimulated ghrelin secretion from mouse ghrelinoma 3‐1, a ghrelin‐releasing cell line. Further on, we characterized the ghrelin‐releasing peptides present in the digest by comprehensive peptide analysis using liquid chromatography–mass spectrometry and structure–activity relationship. Among the candidate peptides, we found that SQQQQPVLPQQPSF, LSVTSPQQVSY and YPTSL stimulated ghrelin release. We then named them wheat‐ghretropin A, B and C, respectively. In addition, we observed that wheat‐ghretropin A increased plasma ghrelin concentration and food intake in mice after oral administration. Thus, we demonstrated that wheat‐ghretropin stimulates ghrelin release both in vitro and in vivo. To the best of our knowledge, this is the first report of a wheat‐derived exogenous bioactive peptide that stimulates ghrelin secretion. By using peptide comprehensive analysis of the gluten digest and by peptide homology comparison with already known ghrelin‐releasing peptides, we discovered three novel peptides that we name wheat‐ghretropins A, B and C. We observed that wheat‐ghretropin A increased food intake and serum ghrelin levels after oral administration in mice. To the best of our knowledge, this is the first report of a wheat‐derived exogenous bioactive peptide that stimulates ghrelin secretion.