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.

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We performed a comprehensive analysis of ghrelin release‐modulating activity of a dipeptide library using MGN3‐1, a ghrelin‐producing cell line. We found that most dipeptides suppress ghrelin secretion, whereas the N‐terminal Ser‐containing dipeptides and a few others stimulate it. N‐terminal amino acid residues, but not C‐terminal residues, play a dominant role in the effects of dipeptides. Among dipeptides, Leu‐Ile (LI) and Ser‐Val (SV) most strongly suppress and stimulate ghrelin secretion, respectively. LI activates Gi signaling and SV acts via the MAPK pathway. Orally administered LI and SV reduce and increase plasma ghrelin levels and food intake in mice, respectively. In conclusion, LI and SV, found based on the comprehensive screening of a dipeptide library, modulate ghrelin secretion in vitro and in vivo.

In this study, we demonstrated that novel rice-derived bioactive peptides promote the secretion of ghrelin, an endogenous orexigenic hormone secreted from the stomach. The enzymatic digest of rice endosperm protein with subtilisin, a microorganism-derived enzyme, stimulated acylated ghrelin secretion in the ghrelin-releasing cell line MGN3-1 and increased food intake after oral administration in mice. By performing a comprehensive analysis based on structure–activity relationships, we selected candidate peptides from over 30,000 peptides in the rice digest. Among them, we found that QAFEPIRSV and TNPWHSPRQGSF, corresponding to the amino acid sequence of the rice endoplasmic proteins glutelin A1 or A2(52-60) and B1 or B2(31-42), respectively, stimulated acylated ghrelin release in MGN3-1 cells. We named them rice-ghretropins A and B. Pyroglutamate formation of rice-ghretropin A, [pyr1]-rice-ghretropin A, also promoted ghrelin secretion. Furthermore, oral administration of rice-ghretropins increased food intake, plasma ghrelin concentration, and small intestinal transit in mice. In addition, the subtilisin digest of the rice protein significantly increased food intake for 4 h in 9 month-old (control: 0.61 ± 0.049 g; digest: 0.83 ± 0.059 g) and 24 month-old mice (control: 0.52 ± 0.067 g; digest: 1.01 ± 0.064 g). In summary, we found that novel bioactive peptides, namely, rice-ghretropins, from the enzymatic digest of rice endosperm stimulated acylated ghrelin secretion and increased food intake. This is the first report of rice-derived exogenous bioactive peptides that increase acylated ghrelin secretion.

Background Salmonella species are a leading cause of diarrheal diseases worldwide. Recent epidemiological studies have shown that Salmonella schwarzengrund (S. schwarzengrund) is highly prevalent in various regions. Herein, we report that S. schwarzengrund caused sacroiliac joint (SIJ) infection with septic shock in a young woman, although she was immunocompetent. Case presentation A 20-year-old woman presented with left hip pain, accompanied by vasopressor-requiring hypotension. Her imaging examinations showed fluid collection in her SIJ and a small abscess in the left iliac muscle. Later, the blood and aspiration fluid culture and genetic analysis revealed the presence of S. schwarzengrund. We diagnosed sacroiliac joint (SIJ) infection with septic shock caused by S. schwarzengrund. Her condition improved after performing several interventional radiology (IVR) procedures for SIJ abscesses and providing appropriate antibiotic treatment. Finally, she was discharged without any sequelae. Screening tests and genetic analysis about her immunodeficiency did not indicate a congenital disorder. Conclusion These clinical courses indicate that S. schwarzengrund could cause the fatal SIJ infection irrespective of the host immunocompetence. Considering the recent increase in the diagnostic rate of S. schwarzengrund, this case emphasized the need to be more cautious about Salmonella species infection.