Comprehensive analysis of a dipeptide library to identify ghrelin release-modulating peptides

FEBS Letters

article

Junya Nakato¹  Hayato Aoki¹  Yuki Tokuyama¹  Yuta Yamamoto¹  Hiroshi Iwakura²  Shigenobu Matsumura¹  Kazuo Inoue¹  Kousaku Ohinata¹ 

[1] Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University;The First Department of Medicine, Wakayama Medical University

关键词: comprehensive analysis;    dipeptide library;    food intake;    ghrelin;    structure–activity relationship;   

DOI  :  10.1002/1873-3468.13522

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 Sercontaining 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.

【 授权许可】

Unknown