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Essential Amino Acid Intake Is Required for Sustaining Serum Insulin-like Growth Factor-I Levels but Is Not Necessarily Needed for Body Growth

Essential amino acids (EAAs) are those that cannot be synthesized enough to meet organismal demand; therefore, it is believed that they must be taken from the diet for optimal growth. The growth hormone (GH)/insulin-like growth factor-I (IGF-I) system is also considered significant for growth regula...

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Autores principales: Nishi, Hiroki, Uchida, Kaito, Saito, Maki, Yamanaka, Daisuke, Nagata, Haruka, Tomoshige, Hinako, Miyata, Ichiro, Ito, Koichi, Toyoshima, Yuka, Takahashi, Shin-Ichiro, Hakuno, Fumihiko, Takenaka, Asako
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9105520/
https://www.ncbi.nlm.nih.gov/pubmed/35563827
http://dx.doi.org/10.3390/cells11091523
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author Nishi, Hiroki
Uchida, Kaito
Saito, Maki
Yamanaka, Daisuke
Nagata, Haruka
Tomoshige, Hinako
Miyata, Ichiro
Ito, Koichi
Toyoshima, Yuka
Takahashi, Shin-Ichiro
Hakuno, Fumihiko
Takenaka, Asako
author_facet Nishi, Hiroki
Uchida, Kaito
Saito, Maki
Yamanaka, Daisuke
Nagata, Haruka
Tomoshige, Hinako
Miyata, Ichiro
Ito, Koichi
Toyoshima, Yuka
Takahashi, Shin-Ichiro
Hakuno, Fumihiko
Takenaka, Asako
author_sort Nishi, Hiroki
collection PubMed
description Essential amino acids (EAAs) are those that cannot be synthesized enough to meet organismal demand; therefore, it is believed that they must be taken from the diet for optimal growth. The growth hormone (GH)/insulin-like growth factor-I (IGF-I) system is also considered significant for growth regulation in mammals. This study aimed to evaluate the relative contributions of protein nutrition and the GH/IGF-I system to body growth regulation. Experiments using rodents and hepatocyte-derived cell lines subjected to EAA deficiency showed that a reduction in the serum EAA concentration hinders Igf1 transcription in the liver in a cell-autonomous manner, thereby decreasing serum IGF-I levels. Remarkably, when the serum IGF-I level of mice on a low-protein diet was restored by the recombinant IGF-I infusion, the body growth was mostly rescued, although the mice were still deficient in EAA intake. Meanwhile, the GH signal activation and subsequent Igf1 transcription were also dramatically diminished by EAA deprivation in the cell culture model. Altogether, we demonstrate that EAAs are not strictly necessary for animal growth as building blocks but are required as IGF-I-tropic cues. The results will bring a paradigm shift regarding the definition of “essential” amino acids.
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spelling pubmed-91055202022-05-14 Essential Amino Acid Intake Is Required for Sustaining Serum Insulin-like Growth Factor-I Levels but Is Not Necessarily Needed for Body Growth Nishi, Hiroki Uchida, Kaito Saito, Maki Yamanaka, Daisuke Nagata, Haruka Tomoshige, Hinako Miyata, Ichiro Ito, Koichi Toyoshima, Yuka Takahashi, Shin-Ichiro Hakuno, Fumihiko Takenaka, Asako Cells Article Essential amino acids (EAAs) are those that cannot be synthesized enough to meet organismal demand; therefore, it is believed that they must be taken from the diet for optimal growth. The growth hormone (GH)/insulin-like growth factor-I (IGF-I) system is also considered significant for growth regulation in mammals. This study aimed to evaluate the relative contributions of protein nutrition and the GH/IGF-I system to body growth regulation. Experiments using rodents and hepatocyte-derived cell lines subjected to EAA deficiency showed that a reduction in the serum EAA concentration hinders Igf1 transcription in the liver in a cell-autonomous manner, thereby decreasing serum IGF-I levels. Remarkably, when the serum IGF-I level of mice on a low-protein diet was restored by the recombinant IGF-I infusion, the body growth was mostly rescued, although the mice were still deficient in EAA intake. Meanwhile, the GH signal activation and subsequent Igf1 transcription were also dramatically diminished by EAA deprivation in the cell culture model. Altogether, we demonstrate that EAAs are not strictly necessary for animal growth as building blocks but are required as IGF-I-tropic cues. The results will bring a paradigm shift regarding the definition of “essential” amino acids. MDPI 2022-05-02 /pmc/articles/PMC9105520/ /pubmed/35563827 http://dx.doi.org/10.3390/cells11091523 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Nishi, Hiroki
Uchida, Kaito
Saito, Maki
Yamanaka, Daisuke
Nagata, Haruka
Tomoshige, Hinako
Miyata, Ichiro
Ito, Koichi
Toyoshima, Yuka
Takahashi, Shin-Ichiro
Hakuno, Fumihiko
Takenaka, Asako
Essential Amino Acid Intake Is Required for Sustaining Serum Insulin-like Growth Factor-I Levels but Is Not Necessarily Needed for Body Growth
title Essential Amino Acid Intake Is Required for Sustaining Serum Insulin-like Growth Factor-I Levels but Is Not Necessarily Needed for Body Growth
title_full Essential Amino Acid Intake Is Required for Sustaining Serum Insulin-like Growth Factor-I Levels but Is Not Necessarily Needed for Body Growth
title_fullStr Essential Amino Acid Intake Is Required for Sustaining Serum Insulin-like Growth Factor-I Levels but Is Not Necessarily Needed for Body Growth
title_full_unstemmed Essential Amino Acid Intake Is Required for Sustaining Serum Insulin-like Growth Factor-I Levels but Is Not Necessarily Needed for Body Growth
title_short Essential Amino Acid Intake Is Required for Sustaining Serum Insulin-like Growth Factor-I Levels but Is Not Necessarily Needed for Body Growth
title_sort essential amino acid intake is required for sustaining serum insulin-like growth factor-i levels but is not necessarily needed for body growth
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9105520/
https://www.ncbi.nlm.nih.gov/pubmed/35563827
http://dx.doi.org/10.3390/cells11091523
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