Importance of Serum Amino Acid Profile for Induction of Hepatic Steatosis under Protein Malnutrition

Nishi, Hisao; Yamanaka, Daisuke; Kamei, Hiroyasu; Goda, Yuki; Kumano, Mikako; Toyoshima, Yuka; Takenaka, Asako; Masuda, Masato; Nakabayashi, Yasushi; Shioya, Ryuji; Kataoka, Naoyuki; Hakuno, Fumihiko; Takahashi, Shin

doi:10.1038/s41598-018-23640-8

Cited by 35 publications

(51 citation statements)

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“…The values are the means ± standard errors. Asterisks indicate significant differences assessed by one-way ANOVA with Bonferroni and Tukey-Kramer post-hoc tests (*p < 0.05) methionine and histidine, were significantly increased by a low Arg diet [10]. Therefore we do not consider arginine alone a signal molecule.…”

Section: Discussionmentioning

confidence: 99%

“…We previously investigated the impacts of various amino acids on fat accumulation in the liver using amino acid-deficient diets, and the results showed that the liver triglyceride (TG) content could be increased only by a deficiency of arginine out of the 20 major amino acids tested [10]. Therefore, we hypothesized that lipid accumulation in the liver induced by dietary amino acid deficiency could be attributed to increased insulin sensitivity, which may be caused specifically by dietary arginine deficiency.…”

Section: Introductionmentioning

confidence: 99%

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Low-arginine and low-protein diets induce hepatic lipid accumulation through different mechanisms in growing rats

et al. 2020

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Background: Dietary protein deficiency and amino acid imbalance cause hepatic fat accumulation. We previously demonstrated that only arginine deficiency or total amino acid deficiency in a diet caused significant hepatic triglyceride (TG) accumulation in young Wistar rats. In this study, we explored the mechanisms of fatty liver formation in these models. Methods: We fed 6-week-old male Wistar rats a control diet (containing an amino acid mixture equivalent to 15% protein), a low-total-amino acid diet (equivalent to 5% protein; 5PAA), and a low-arginine diet (only the arginine content is as low as that of the 5PAA diet) for 2 weeks. Results: Much greater hepatic TG accumulation was observed in the low-arginine group than in the low-totalamino acid group. The lipid consumption rate and fatty acid uptake in the liver did not significantly differ between the groups. In contrast, the low-total-amino acid diet potentiated insulin sensitivity and related signaling in the liver and enhanced de novo lipogenesis. The low-arginine diet also inhibited hepatic very-low-density lipoprotein secretion without affecting hepatic insulin signaling and lipogenesis. Conclusions: Although the arginine content of the low-arginine diet was as low as that of the low-total-amino acid diet, the two diets caused fatty liver via completely different mechanisms. Enhanced lipogenesis was the primary cause of a low-protein diet-induced fatty liver, whereas lower very-low-density lipoprotein secretion caused low-arginine diet-induced fatty liver.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Low-arginine and low-protein diets induce hepatic lipid accumulation through different mechanisms in growing rats

et al. 2020

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“…The activation of this pathway is known to upregulate FFA synthesis [9,[29][30][31], and, indeed, increased de novo lipogenesis was observed in 5PAA dietfed rats. In contrast, we recently reported that when hepatocytes were cultured in an amino acid-su cient or -de cient medium, the intracellular TG level was increased by amino acid de ciency without the addition of any lipids or hormones, and was accompanied by enhanced lipid synthesis [10]. These results indicate that hepatocytes themselves monitor extracellular amino acid concentrations to induce lipid accumulation in a cell-autonomous manner.…”

Section: Discussionmentioning

confidence: 76%

Low-arginine and low-protein diets induce hepatic lipid accumulation through different mechanisms in growing rats

Otani¹,

Nishi

Koyama

et al. 2020

Preprint

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Background Dietary protein deficiency and amino acid imbalance cause hepatic fat accumulation. We previously demonstrated that only arginine deficiency or total amino acid deficiency in a diet caused significant hepatic triglyceride (TG) accumulation in young Wistar rats. In this study, we explored the mechanisms of fatty liver formation in these models.Dietary protein deficiency and amino acid imbalance cause hepatic fat accumulation. We previously demonstrated that only arginine deficiency or total amino acid deficiency in a diet caused significant hepatic triglyceride (TG) accumulation in young Wistar rats. In this study, we explored the mechanisms of fatty liver formation in these models. Methods We fed 6-week-old male Wistar rats a control diet (containing an amino acid mixture equivalent to 15% protein), a low-total-amino acid diet (equivalent to 5% protein; 5PAA), and a low-arginine diet (only the arginine content is as low as that of the 5PAA diet) for 2 weeks. Results Much greater hepatic TG accumulation was observed in the low-arginine group than in the low-total-amino acid group. The lipid consumption rate and fatty acid uptake in the liver did not significantly differ between the groups. In contrast, the low-total-amino acid diet potentiated insulin sensitivity and related signaling in the liver and enhanced de novo lipogenesis. The low-arginine diet also inhibited hepatic very-low-density lipoprotein secretion without affecting hepatic insulin signaling and lipogenesis. Conclusions : Although the arginine content of the low-arginine diet was as low as that of the low-total-amino acid diet, the two diets caused fatty liver via completely different mechanisms. Enhanced lipogenesis was the primary cause of a low-protein diet-induced fatty liver, whereas lower very-low-density lipoprotein secretion caused low-arginine diet-induced fatty liver.

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“…The activation of this pathway is known to upregulate FFA synthesis [9,[29][30][31], and, indeed, increased de novo lipogenesis was observed in 5PAA diet-fed rats. In contrast, we recently reported that when hepatocytes were cultured in an amino acidsu cient or -de cient medium, the intracellular TG level was increased by amino acid de ciency without the addition of any lipids or hormones, and was accompanied by enhanced lipid synthesis [10]. These results indicate that hepatocytes themselves monitor extracellular amino acid concentrations to induce lipid accumulation in a cell-autonomous manner.…”

Section: Discussionmentioning

confidence: 76%

“…We previously investigated the impacts of various amino acids on fat accumulation in the liver using amino acid-de cient diets, and the results showed that the liver triglyceride (TG) content could be increased only by a de ciency of arginine out of the 20 major amino acids tested [10]. Therefore, we hypothesized that lipid accumulation in the liver induced by dietary amino acid de ciency could be attributed to increased insulin sensitivity, which may be caused speci cally by dietary arginine de ciency.…”

Section: Introductionmentioning

confidence: 99%

Low-arginine and low-protein diets induce hepatic lipid accumulation through different mechanisms in growing rats

Otani

Nishi

Koyama

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

Background: Dietary protein deficiency and amino acid imbalance cause hepatic fat accumulation. We previously demonstrated that only arginine deficiency or total amino acid deficiency in a diet caused significant hepatic triglyceride (TG) accumulation in young Wistar rats. In this study, we explored the mechanisms of fatty liver formation in these models.Methods: We fed 6-week-old male Wistar rats a control diet (containing an amino acid mixture equivalent to 15% protein), a low-total-amino acid diet (equivalent to 5% protein; 5PAA), and a low-arginine diet (only the arginine content is as low as that of the 5PAA diet) for 2 weeks.Results: Much greater hepatic TG accumulation was observed in the low-arginine group than in the low-total-amino acid group. The lipid consumption rate and fatty acid uptake in the liver did not significantly differ between the groups. In contrast, the low-total-amino acid diet potentiated insulin sensitivity and related signaling in the liver and enhanced de novo lipogenesis. The low-arginine diet also inhibited hepatic very-low-density lipoprotein secretion without affecting hepatic insulin signaling and lipogenesis.Conclusions: Although the arginine content of the low-arginine diet was as low as that of the low-total-amino acid diet, the two diets caused fatty liver via completely different mechanisms. Enhanced lipogenesis was the primary cause of a low-protein diet-induced fatty liver, whereas lower very-low-density lipoprotein secretion caused low-arginine diet-induced fatty liver.

show abstract

Importance of Serum Amino Acid Profile for Induction of Hepatic Steatosis under Protein Malnutrition

Cited by 35 publications

References 35 publications

Low-arginine and low-protein diets induce hepatic lipid accumulation through different mechanisms in growing rats

Low-arginine and low-protein diets induce hepatic lipid accumulation through different mechanisms in growing rats

Low-arginine and low-protein diets induce hepatic lipid accumulation through different mechanisms in growing rats

Low-arginine and low-protein diets induce hepatic lipid accumulation through different mechanisms in growing rats

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