Alteration of serum amino acid profiles by dietary adenine supplementation inhibits fatty liver development in rats

Abstract Studies on animal models have demonstrated that feeding a low-arginine diet inhibits triacylglycerol (TAG) secretion from the liver, resulting in marked fatty liver development in rats. Here, we first showed that culturing hepatocytes in the medium mimicking the serum amino acid profile of...

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Autores principales:	Hiroki Nishi, Daisuke Yamanaka, Masato Masuda, Yuki Goda, Koichi Ito, Fumihiko Hakuno, Shin-Ichiro Takahashi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/da3c335dee9348e3be7270e3b497e1fa
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spelling	oai:doaj.org-article:da3c335dee9348e3be7270e3b497e1fa2021-12-02T13:58:16ZAlteration of serum amino acid profiles by dietary adenine supplementation inhibits fatty liver development in rats10.1038/s41598-020-79234-w2045-2322https://doaj.org/article/da3c335dee9348e3be7270e3b497e1fa2020-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-79234-whttps://doaj.org/toc/2045-2322Abstract Studies on animal models have demonstrated that feeding a low-arginine diet inhibits triacylglycerol (TAG) secretion from the liver, resulting in marked fatty liver development in rats. Here, we first showed that culturing hepatocytes in the medium mimicking the serum amino acid profile of low-arginine diet-fed rats induced TAG accumulation in the cells, indicating that the specific amino acid profile caused TAG accumulation in hepatocytes. Dietary adenine supplementation completely recovered hepatic TAG secretion and abolished hepatic TAG accumulation in rats. A comprehensive non-linear analysis revealed that inhibition of hepatic TAG accumulation by dietary adenine supplementation could be predicted using only serum amino acid concentration data. Comparison of serum amino acid concentrations indicated that histidine, methionine, and branched-chain amino acid (BCAA) concentrations were altered by adenine supplementation. Furthermore, when the serum amino acid profiles of low-arginine diet-fed rats were altered by modifying methionine or BCAA concentrations in their diets, their hepatic TAG accumulation was abolished. Altogether, these results suggest that an increase in methionine and BCAA levels in the serum in response to dietary arginine deficiency is a key causative factor for hepatic TAG accumulation, and dietary adenine supplementation could disrupt this phenomenon by altering serum amino acid profiles.Hiroki NishiDaisuke YamanakaMasato MasudaYuki GodaKoichi ItoFumihiko HakunoShin-Ichiro TakahashiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-10 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hiroki Nishi Daisuke Yamanaka Masato Masuda Yuki Goda Koichi Ito Fumihiko Hakuno Shin-Ichiro Takahashi Alteration of serum amino acid profiles by dietary adenine supplementation inhibits fatty liver development in rats
description	Abstract Studies on animal models have demonstrated that feeding a low-arginine diet inhibits triacylglycerol (TAG) secretion from the liver, resulting in marked fatty liver development in rats. Here, we first showed that culturing hepatocytes in the medium mimicking the serum amino acid profile of low-arginine diet-fed rats induced TAG accumulation in the cells, indicating that the specific amino acid profile caused TAG accumulation in hepatocytes. Dietary adenine supplementation completely recovered hepatic TAG secretion and abolished hepatic TAG accumulation in rats. A comprehensive non-linear analysis revealed that inhibition of hepatic TAG accumulation by dietary adenine supplementation could be predicted using only serum amino acid concentration data. Comparison of serum amino acid concentrations indicated that histidine, methionine, and branched-chain amino acid (BCAA) concentrations were altered by adenine supplementation. Furthermore, when the serum amino acid profiles of low-arginine diet-fed rats were altered by modifying methionine or BCAA concentrations in their diets, their hepatic TAG accumulation was abolished. Altogether, these results suggest that an increase in methionine and BCAA levels in the serum in response to dietary arginine deficiency is a key causative factor for hepatic TAG accumulation, and dietary adenine supplementation could disrupt this phenomenon by altering serum amino acid profiles.
format	article
author	Hiroki Nishi Daisuke Yamanaka Masato Masuda Yuki Goda Koichi Ito Fumihiko Hakuno Shin-Ichiro Takahashi
author_facet	Hiroki Nishi Daisuke Yamanaka Masato Masuda Yuki Goda Koichi Ito Fumihiko Hakuno Shin-Ichiro Takahashi
author_sort	Hiroki Nishi
title	Alteration of serum amino acid profiles by dietary adenine supplementation inhibits fatty liver development in rats
title_short	Alteration of serum amino acid profiles by dietary adenine supplementation inhibits fatty liver development in rats
title_full	Alteration of serum amino acid profiles by dietary adenine supplementation inhibits fatty liver development in rats
title_fullStr	Alteration of serum amino acid profiles by dietary adenine supplementation inhibits fatty liver development in rats
title_full_unstemmed	Alteration of serum amino acid profiles by dietary adenine supplementation inhibits fatty liver development in rats
title_sort	alteration of serum amino acid profiles by dietary adenine supplementation inhibits fatty liver development in rats
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/da3c335dee9348e3be7270e3b497e1fa
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Alteration of serum amino acid profiles by dietary adenine supplementation inhibits fatty liver development in rats

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