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...

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Autores principales:	Yuna Lee, Akihiro Nakano, Saya Nakamura, Kenta Sakai, Mitsuru Tanaka, Keisuke Sanematsu, Noriatsu Shigemura, Toshiro Matsui
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Nutrition. Foods and food supply TX341-641 Food processing and manufacture TP368-456
Acceso en línea:	https://doaj.org/article/d6a6f6a590ac47a8ae6ba0208904792b
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spelling	oai:doaj.org-article:d6a6f6a590ac47a8ae6ba0208904792b2021-11-14T12:38:49ZIn vitro and in silico characterization of adiponectin-receptor agonist dipeptides10.1038/s41538-021-00114-22396-8370https://doaj.org/article/d6a6f6a590ac47a8ae6ba0208904792b2021-11-01T00:00:00Zhttps://doi.org/10.1038/s41538-021-00114-2https://doaj.org/toc/2396-8370Abstract 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.Yuna LeeAkihiro NakanoSaya NakamuraKenta SakaiMitsuru TanakaKeisuke SanematsuNoriatsu ShigemuraToshiro MatsuiNature PortfolioarticleNutrition. Foods and food supplyTX341-641Food processing and manufactureTP368-456ENnpj Science of Food, Vol 5, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Nutrition. Foods and food supply TX341-641 Food processing and manufacture TP368-456
spellingShingle	Nutrition. Foods and food supply TX341-641 Food processing and manufacture TP368-456 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
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.
format	article
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
title	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_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_sort	in vitro and in silico characterization of adiponectin-receptor agonist dipeptides
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/d6a6f6a590ac47a8ae6ba0208904792b
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In vitro and in silico characterization of adiponectin-receptor agonist dipeptides

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