In vitro and in silico characterization of adiponectin-receptor agonist dipeptides
Abstract The aim of this study is to develop a dipeptide showing an adiponectin receptor 1 (AdipoR1) agonistic effect in skeletal muscle L6 myotubes. Based on the structure of the AdipoR1 agonist, AdipoRon, 15 synthetic dipeptides were targeted to promote glucose uptake in L6 myotubes. Tyr-Pro showe...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2021-11-01
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| Series: | npj Science of Food |
| Online Access: | https://doi.org/10.1038/s41538-021-00114-2 |
| _version_ | 1818932845891026944 |
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| author | Yuna Lee Akihiro Nakano Saya Nakamura Kenta Sakai Mitsuru Tanaka Keisuke Sanematsu Noriatsu Shigemura Toshiro Matsui |
| author_facet | Yuna Lee Akihiro Nakano Saya Nakamura Kenta Sakai Mitsuru Tanaka Keisuke Sanematsu Noriatsu Shigemura Toshiro Matsui |
| author_sort | Yuna Lee |
| collection | DOAJ |
| description | Abstract The aim of this study is to develop a dipeptide showing an adiponectin receptor 1 (AdipoR1) agonistic effect in skeletal muscle L6 myotubes. Based on the structure of the AdipoR1 agonist, AdipoRon, 15 synthetic dipeptides were targeted to promote glucose uptake in L6 myotubes. Tyr-Pro showed a significant increase in glucose uptake among the dipeptides, while other dipeptides, including Pro-Tyr, failed to exert this effect. Tyr-Pro induces glucose transporter 4 (Glut4) expression in the plasma membrane, along with adenosine monophosphate-activated protein kinase (AMPK) activation. In AdipoR1-knocked down cells, the promotion by Tyr-Pro was ameliorated, indicating that Tyr-Pro may directly interact with AdipoR1 as an agonist, followed by the activation of AMPK/Glut4 translocation in L6 myotubes. Molecular dynamics simulations revealed that a Tyr-Pro molecule was stably positioned in the two potential binding pockets (sites 1 and 2) of the seven-transmembrane receptor, AdipoR1, anchored in a virtual 1-palmitoyl-2-oleoyl-phosphatidylcholine membrane. In conclusion, we demonstrated the antidiabetic function of the Tyr-Pro dipeptide as a possible AdipoR1 agonist. |
| first_indexed | 2024-12-20T04:38:58Z |
| format | Article |
| id | doaj.art-d6a6f6a590ac47a8ae6ba0208904792b |
| institution | Directory Open Access Journal |
| issn | 2396-8370 |
| language | English |
| last_indexed | 2024-12-20T04:38:58Z |
| publishDate | 2021-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Science of Food |
| spelling | doaj.art-d6a6f6a590ac47a8ae6ba0208904792b2022-12-21T19:53:11ZengNature Portfolionpj Science of Food2396-83702021-11-015111010.1038/s41538-021-00114-2In vitro and in silico characterization of adiponectin-receptor agonist dipeptidesYuna Lee0Akihiro Nakano1Saya Nakamura2Kenta Sakai3Mitsuru Tanaka4Keisuke Sanematsu5Noriatsu Shigemura6Toshiro Matsui7Department of Bioresources and Biosciences, Faculty of Agriculture, Graduate School of Kyushu UniversityDepartment of Bioresources and Biosciences, Faculty of Agriculture, Graduate School of Kyushu UniversityDepartment of Bioresources and Biosciences, Faculty of Agriculture, Graduate School of Kyushu UniversityResearch and Development Center for Five-Sense Devices, Kyushu UniversityResearch and Development Center for Five-Sense Devices, Kyushu UniversityResearch and Development Center for Five-Sense Devices, Kyushu UniversityResearch and Development Center for Five-Sense Devices, Kyushu UniversityDepartment of Bioresources and Biosciences, Faculty of Agriculture, Graduate School of Kyushu UniversityAbstract The aim of this study is to develop a dipeptide showing an adiponectin receptor 1 (AdipoR1) agonistic effect in skeletal muscle L6 myotubes. Based on the structure of the AdipoR1 agonist, AdipoRon, 15 synthetic dipeptides were targeted to promote glucose uptake in L6 myotubes. Tyr-Pro showed a significant increase in glucose uptake among the dipeptides, while other dipeptides, including Pro-Tyr, failed to exert this effect. Tyr-Pro induces glucose transporter 4 (Glut4) expression in the plasma membrane, along with adenosine monophosphate-activated protein kinase (AMPK) activation. In AdipoR1-knocked down cells, the promotion by Tyr-Pro was ameliorated, indicating that Tyr-Pro may directly interact with AdipoR1 as an agonist, followed by the activation of AMPK/Glut4 translocation in L6 myotubes. Molecular dynamics simulations revealed that a Tyr-Pro molecule was stably positioned in the two potential binding pockets (sites 1 and 2) of the seven-transmembrane receptor, AdipoR1, anchored in a virtual 1-palmitoyl-2-oleoyl-phosphatidylcholine membrane. In conclusion, we demonstrated the antidiabetic function of the Tyr-Pro dipeptide as a possible AdipoR1 agonist.https://doi.org/10.1038/s41538-021-00114-2 |
| spellingShingle | Yuna Lee Akihiro Nakano Saya Nakamura Kenta Sakai Mitsuru Tanaka Keisuke Sanematsu Noriatsu Shigemura Toshiro Matsui In vitro and in silico characterization of adiponectin-receptor agonist dipeptides npj Science of Food |
| title | In vitro and in silico characterization of adiponectin-receptor agonist dipeptides |
| title_full | In vitro and in silico characterization of adiponectin-receptor agonist dipeptides |
| title_fullStr | In vitro and in silico characterization of adiponectin-receptor agonist dipeptides |
| title_full_unstemmed | In vitro and in silico characterization of adiponectin-receptor agonist dipeptides |
| title_short | In vitro and in silico characterization of adiponectin-receptor agonist dipeptides |
| title_sort | in vitro and in silico characterization of adiponectin receptor agonist dipeptides |
| url | https://doi.org/10.1038/s41538-021-00114-2 |
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