Performance information

• Apolipoprotein b transcription is driven by ornithine in hepatoma cell lines.　　　　　　　　　　　　　　　
  Hiroki Nishi; Sena Nakanishi; Daisuke Yamanaka; Shin-Ichiro Takahashi; Fumihiko Hakuno
  Biochemical and biophysical research communications, Volume：775, First page：152076, Last page：152076, May 2025, [Reviewed], [Lead, Corresponding], ［International magazine］
  The liver is a central metabolic organ, and nutritional status, such as protein/amino acid malnutrition, significantly affects metabolic homeostasis. When animals are fed an amino acid-restricted diet, triglyceride-rich very low-density lipoprotein (VLDL) secretion is lowered, leading to fatty liver development. Therefore, we have explored the effects of amino acids on the expression of Apolipoprotein b (Apob), the main VLDL component, using a hepatoma cell culture model. When H4IIE rat hepatoma cells were cultured in an amino acid-depleted medium, Apob mRNA levels were significantly lower than those in control cells. In addition, when cells were cultured in media deprived of a single amino acid, aspartic or glutamic acid deprivation decreased Apob mRNA levels, whereas depletion of lysine, histidine, threonine, leucine, or isoleucine increased it. To understand the interrelationship between these extracellular amino acids and Apob transcription, metabolome analysis of these cells was performed. The intracellular methionine, adenine, and ornithine levels were positively correlated with Apob mRNA levels. Among them, only ornithine significantly enhanced Apob transcription, when added to the amino acid-depleted medium. In summary, these results suggest that ornithine plays a key role in Apob transcriptional regulation, corresponding to changes in extracellular amino acid concentrations.
  English, Scientific journal
  DOI：https://doi.org/10.1016/j.bbrc.2025.152076
  DOI ID：10.1016/j.bbrc.2025.152076, PubMed ID：40466366
• Insulin Receptor Substrate-2 Regulates the Secretion of Growth Factors in Response to Amino Acid Deprivation.　　　　　　　　　　　　　　　
  Ayaka Takahashi; Haruka Furuta; Hiroki Nishi; Hiroyasu Kamei; Shin-Ichiro Takahashi; Fumihiko Hakuno
  International journal of molecular sciences, Volume：26, Number：2, Jan. 2025, [Reviewed], ［International magazine］
  Insulin receptor substrates (IRSs) are well-known mediators of the insulin and insulin-like growth factor (IGF)-I signaling pathways. We previously reported that the protein levels of IRS-2, a molecular species of IRS, were upregulated in the livers of rats fed a protein-restricted diet. This study aimed to elucidate the physiological role of IRS-2, whose level increases in response to protein restriction in cultured hepatocyte models. Hepatocyte-derived cell lines subjected to amino acid deprivation showed increased IRS2 mRNA and IRS-2 protein levels due to increased IRS2 transcription and translation, respectively. Amino acid deprivation markedly increased vascular endothelial growth factor-D (VEGF-D) secretion. Remarkably, the amino acid deprivation-induced VEGF-D secretion was suppressed by IRS-2 knockdown and enhanced by IRS-2 overexpression. These results suggest that IRS-2 is an intercellular signaling molecule that extracellularly transmits information on amino acid deprivation stress by regulating the secretion of growth factors such as VEGF-D. Moreover, this function of IRS-2 is distinct from its currently accepted function as a mediator of the insulin/IGF-I signaling pathways. This study demonstrates that IRS-2 can modulate protein secretion in an insulin-independent manner and greatly expands our understanding of the role of IRS-2, which is upregulated in response to amino acid deprivation.
  English, Scientific journal
  DOI：https://doi.org/10.3390/ijms26020841
  DOI ID：10.3390/ijms26020841, PubMed ID：39859555, PubMed Central ID：PMC11766276
• Metabolic Effects of Short-Term High-Fat Intake Vary Depending on Dietary Amino Acid Composition.　　　　　　　　　　　　　　　
  Hiroki Nishi; Yuki Goda; Ryosuke Okino; Ruri Iwai; Reona Maezawa; Koichi Ito; Shin-Ichiro Takahashi; Daisuke Yamanaka; Fumihiko Hakuno
  Current developments in nutrition, Volume：8, Number：6, First page：103768, Last page：103768, Jun. 2024, [Reviewed], ［International magazine］
  BACKGROUND: It is generally accepted that excessive fat intake has undesirable effects on the energy metabolism of our body. Dietary amino acid composition is also critical to the regulation of lipid metabolism. OBJECTIVES: This study aimed to investigate whether high-fat diets (HFDs) with different amino acid deficiencies lead to different metabolic outcomes. METHODS: Six-wk-old male Wistar rats were fed either a control diet (CN; 3.7 kcal/g, 12% calories from fat) or HFDs (5.1 kcal/g, 60% calories from fat) with 7 different amino acid compositions [control or methionine, arginine, histidine, lysine, threonine, or branched-chain amino acids (BCAAs) deficient], for 7 d. Tissue weights and lipid accumulation in the liver, skeletal muscle, and adipose tissue were measured, and serum biochemical parameters were analyzed. RESULTS: Although the food intake of the HFD groups was a little less than that of the CN group, the total calorie intakes were comparable among the groups, except for histidine-deficient and BCAA-deficient groups. In rats fed am HFD with a control amino acid composition (HFCN), dramatic increase in triglyceride (TG) accumulation in the liver and serum LDL cholesterol concentration were observed compared with the CN group. However, when the arginine content in the diet was reduced, liver TG accumulation was completely inhibited, with no apparent effects on serum lipoprotein-cholesterol concentrations. Meanwhile, deficiency of the other amino acids, such as threonine, reversed HFD-induced upregulation of serum LDL cholesterol. CONCLUSIONS: It is observed that although the rats ingested an excessive amount of fat, neither ectopic fat accumulation nor dyslipidemia were always induced at least in the short term; hence, the consequent metabolic change was dependent on the dietary amino acid composition. These findings introduce an important perspective regarding HFD regimens in both scientific and clinical contexts.
  English, Scientific journal
  DOI：https://doi.org/10.1016/j.cdnut.2024.103768
  DOI ID：10.1016/j.cdnut.2024.103768, PubMed ID：38939648, PubMed Central ID：PMC11208941
• Growth hormone resistance induced by amino acid deprivation in fao cells is independent of FGF21.　　　　　　　　　　　　　　　
  Maki Saito; Hiroki Nishi; Shin-Ichiro Takahashi; Fumihiko Hakuno; Ichiro Miyata
  Biochemical and biophysical research communications, Volume：709, First page：149811, Last page：149811, May 2024, [Reviewed], ［International magazine］
  Adequate dietary intake of amino acids is imperative for normal animal growth. Our previous work using rat hepatocarcinoma Fao cells demonstrated that growth hormone (GH) resistance, coupled with a concurrent reduction in insulin-like growth factor 1 (Igf1) mRNA levels, may underlie the growth retardation associated with a low-protein diet (LPD). In this study, we investigated whether FGF21 contributes to liver GH resistance in Fao rat hepatoma cells under amino acid deprivation conditions. Mice subjected to an LPD exhibited growth retardation, compromised GH signaling in the liver, and decreased blood IGF-1 levels compared with those on a control diet. To assess the potential involvement of fibroblast growth factor (FGF) 21, produced in response to amino acid deficiency, in the development of GH resistance, we examined GH signaling and Igf1 mRNA levels in Fao cells cultured in amino acid-deprived medium. Despite the inhibition of Fgf21 expression by the integrated stress response inhibitor, an inhibitor of the eukaryotic initiation factor 2-activating transcription factor 4 pathway, GH resistance persisted in response to amino acid deprivation. Additionally, the introduction of FGF21 into the control medium did not impair either GH signaling or GH-induced Igf1 transcription. These data suggest that, in Fao cells, amino acid deprivation induces GH resistance independently of FGF21 activity. By shedding light on the mechanisms behind growth retardation-associated GH resistance linked to amino acid deficiencies, our findings provide valuable insights for clinicians in formulating effective treatment strategies for individuals facing these challenges.
  English, Scientific journal
  DOI：https://doi.org/10.1016/j.bbrc.2024.149811
  DOI ID：10.1016/j.bbrc.2024.149811, PubMed ID：38569244
• Moderate protein intake percentage in mice for maintaining metabolic health during approach to old age.　　　　　　　　　　　　　　　
  Yoshitaka Kondo; Hitoshi Aoki; Masato Masuda; Hiroki Nishi; Yoshihiro Noda; Fumihiko Hakuno; Shin-Ichiro Takahashi; Takuya Chiba; Akihito Ishigami
  GeroScience, Volume：45, Number：4, First page：2707, Last page：2726, Aug. 2023, [Reviewed], ［International magazine］
  Nutritional requirements for maintaining metabolic health may vary with each life stage, such as young, middle, and old age. To investigate the appropriate ratio of nutrients, particularly proteins, for maintaining metabolic health while approaching old age, young (6-month-old) and middle-aged (16-month-old) mice were fed isocaloric diets with varying protein percentages (5%, 15%, 25%, 35%, and 45% by calorie ratio) for two months. The low-protein diet developed mild fatty liver, with middle-aged mice showing more lipids than young mice, whereas the moderate-protein diet suppressed lipid contents and lowered the levels of blood glucose and lipids. Self-organizing map (SOM) analysis revealed that plasma amino acid profiles differed depending on age and difference in protein diet and were associated with hepatic triglyceride and cholesterol levels. Results indicate that the moderate protein intake percentages (25% and 35%) are required for maintaining metabolic health in middle-aged mice, which is similar to that in young mice.
  English, Scientific journal
  DOI：https://doi.org/10.1007/s11357-023-00797-3
  DOI ID：10.1007/s11357-023-00797-3, PubMed ID：37118349, PubMed Central ID：PMC10651611
• Macroglossia and less advanced dystrophic change in the tongue muscle of the Duchenne muscular dystrophy rat.　　　　　　　　　　　　　　　
  Keitaro Yamanouchi; Yukie Tanaka; Masanari Ikeda; Shizuka Kato; Ryosuke Okino; Hiroki Nishi; Fumihiko Hakuno; Shin-Ichiro Takahashi; James Chambers; Takashi Matsuwaki; Kazuyuki Uchida
  Skeletal muscle, Volume：12, Number：1, First page：24, Last page：24, Oct. 2022, [Reviewed], ［International magazine］
  BACKGROUND: Duchenne muscular dystrophy (DMD) is an X-linked muscle disease caused by a complete lack of dystrophin, which stabilizes the plasma membrane of myofibers. The orofacial function is affected in an advanced stage of DMD and this often leads to an eating disorder such as dysphagia. Dysphagia is caused by multiple etiologies including decreased mastication and swallowing. Therefore, preventing the functional declines of mastication and swallowing in DMD is important to improve the patient's quality of life. In the present study, using a rat model of DMD we generated previously, we performed analyses on the masseter and tongue muscles, both are required for proper eating function. METHODS: Age-related changes of the masseter and tongue muscle of DMD rats were analyzed morphometrically, histologically, and immunohistochemically. Also, transcription of cellular senescent markers, and utrophin (Utrn), a functional analog of dystrophin, was examined. RESULTS: The masseter muscle of DMD rats showed progressive dystrophic changes as observed in their hindlimb muscle, accompanied by increased transcription of p16 and p19. On the other hand, the tongue of DMD rats showed macroglossia due to hypertrophy of myofibers with less dystrophic changes. Proliferative activity was preserved in the satellite cells from the tongue muscle but was perturbed severely in those from the masseter muscle. While Utrn transcription was increased in the masseter muscle of DMD rats compared to WT rats, probably due to a compensatory mechanism, its level in the tongue muscle was comparable between WT and DMD rats and was similar to that in the masseter muscle of DMD rats. CONCLUSIONS: Muscular dystrophy is less advanced in the tongue muscle compared to the masseter muscle in the DMD rat.
  English, Scientific journal
  DOI：https://doi.org/10.1186/s13395-022-00307-7
  DOI ID：10.1186/s13395-022-00307-7, PubMed ID：36258243, PubMed Central ID：PMC9580129
• Essential Amino Acid Intake Is Required for Sustaining Serum Insulin-like Growth Factor-I Levels but Is Not Necessarily Needed for Body Growth.　　　　　　　　　　　　　　　
  Hiroki Nishi; Kaito Uchida; Maki Saito; Daisuke Yamanaka; Haruka Nagata; Hinako Tomoshige; Ichiro Miyata; Koichi Ito; Yuka Toyoshima; Shin-Ichiro Takahashi; Fumihiko Hakuno; Asako Takenaka
  Cells, Volume：11, Number：9, May 2022, [Reviewed], ［International magazine］
  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.
  English, Scientific journal
  DOI：https://doi.org/10.3390/cells11091523
  DOI ID：10.3390/cells11091523, PubMed ID：35563827, PubMed Central ID：PMC9105520
• Dietary lysine restriction induces lipid accumulation in skeletal muscle through an increase in serum threonine levels in rats.　　　　　　　　　　　　　　　
  Yuki Goda; Daisuke Yamanaka; Hiroki Nishi; Masato Masuda; Hiroyasu Kamei; Mikako Kumano; Koichi Ito; Masaya Katsumata; Keitaro Yamanouchi; Naoyuki Kataoka; Fumihiko Hakuno; Shin-Ichiro Takahashi
  The Journal of biological chemistry, Volume：297, Number：4, First page：101179, Last page：101179, Oct. 2021, [Reviewed], ［International magazine］
  We previously reported that dietary amino acid restriction induces the accumulation of triglycerides (TAG) in the liver of growing rats. However, differences in TAG accumulation in individual cell types or other tissues were not examined. In this study, we show that TAG also accumulates in the muscle and adipose tissues of rats fed a low amino acid (low-AA) diet. In addition, dietary lysine restriction (low-Lys) induces lipid accumulation in muscle and adipose tissues. In adjusting the nitrogen content to that of the control diet, we found that glutamic acid supplementation to the low-AA diet blocked lipid accumulation, but supplementation with the low-Lys diet did not, suggesting that a shortage of nitrogen caused lipids to accumulate in the skeletal muscle in the rats fed a low-AA diet. Serum amino acid measurement revealed that, in rats fed a low-Lys diet, serum lysine levels were decreased, while serum threonine levels were significantly increased compared with the control rats. When the threonine content was restricted in the low-Lys diet, TAG accumulation induced by the low-Lys diet was completely abolished in skeletal muscle. Moreover, in L6 myotubes cultured in medium containing high threonine and low lysine, fatty acid uptake was enhanced compared with that in cells cultured in control medium. These findings suggest that the increased serum threonine in rats fed a low-Lys diet resulted in lipid incorporation into skeletal muscle, leading to the formation of fatty muscle tissue. Collectively, we propose conceptual hypothesis that "amino-acid signal" based on lysine and threonine regulates lipid metabolism.
  English, Scientific journal
  DOI：https://doi.org/10.1016/j.jbc.2021.101179
  DOI ID：10.1016/j.jbc.2021.101179, PubMed ID：34508782, PubMed Central ID：PMC8488598
• A novel amino acid signaling process governs glucose-6-phosphatase transcription.　　　　　　　　　　　　　　　
  Sara Fukushima; Hiroki Nishi; Mikako Kumano; Daisuke Yamanaka; Naoyuki Kataoka; Fumihiko Hakuno; Shin-Ichiro Takahashi
  iScience, Volume：24, Number：7, First page：102778, Last page：102778, Jul. 2021, [Reviewed], ［International magazine］
  Emerging evidence has shown that amino acids act as metabolic regulatory signals. Here, we showed that glucose-6-phosphatase (G6Pase) mRNA levels in cultured hepatocyte models were downregulated in an amino-acid-depleted medium. Inversely, stimulation with amino acids increased G6Pase mRNA levels, demonstrating that G6Pase mRNA level is directly controlled by amino acids in a reversible manner. Promoter assay revealed that these amino-acid-mediated changes in G6Pase mRNA levels were attributable to transcriptional regulation, independent of canonical hormone signaling pathways. Metabolomic analysis revealed that amino acid starvation induces a defect in the urea cycle, decreasing ornithine, a major intermediate, and supplementation of ornithine in an amino-acid-depleted medium fully rescued G6Pase mRNA transcription, similar to the effects of amino acid stimulation. This pathway was also independent of established mammalian target of rapamycin complex 1 pathway. Collectively, we present a hypothetical concept of "metabolic regulatory amino acid signal," possibly mediated by ornithine.
  English, Scientific journal
  DOI：https://doi.org/10.1016/j.isci.2021.102778
  DOI ID：10.1016/j.isci.2021.102778, PubMed ID：34278273, PubMed Central ID：PMC8267547
• Alteration of serum amino acid profiles by dietary adenine supplementation inhibits fatty liver development in rats.　　　　　　　　　　　　　　　
  Hiroki Nishi; Daisuke Yamanaka; Masato Masuda; Yuki Goda; Koichi Ito; Fumihiko Hakuno; Shin-Ichiro Takahashi
  Scientific reports, Volume：10, Number：1, First page：22110, Last page：22110, Dec. 2020, [Reviewed], ［International magazine］
  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.
  English, Scientific journal
  DOI：https://doi.org/10.1038/s41598-020-79234-w
  DOI ID：10.1038/s41598-020-79234-w, PubMed ID：33335253, PubMed Central ID：PMC7747621
• Low-arginine and low-protein diets induce hepatic lipid accumulation through different mechanisms in growing rats.　　　　　　　　　　　　　　　
  Lila Otani; Hiroki Nishi; Ayaka Koyama; Yuta Akasaka; Yusuke Taguchi; Yuka Toyoshima; Daisuke Yamanaka; Fumihiko Hakuno; Huijuan Jia; Shin-Ichiro Takahashi; Hisanori Kato
  Nutrition & metabolism, Volume：17, First page：60, Last page：60, 2020, [Reviewed], ［International magazine］
  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.
  English, Scientific journal
  DOI：https://doi.org/10.1186/s12986-020-00477-5
  DOI ID：10.1186/s12986-020-00477-5, PubMed ID：32774438, PubMed Central ID：PMC7398226
• Importance of Serum Amino Acid Profile for Induction of Hepatic Steatosis under Protein Malnutrition.　　　　　　　　　　　　　　　
  Hiroki Nishi; Daisuke Yamanaka; Hiroyasu Kamei; Yuki Goda; Mikako Kumano; Yuka Toyoshima; Asako Takenaka; Masato Masuda; Yasushi Nakabayashi; Ryuji Shioya; Naoyuki Kataoka; Fumihiko Hakuno; Shin-Ichiro Takahashi
  Scientific reports, Volume：8, Number：1, First page：5461, Last page：5461, Apr. 2018, [Reviewed], ［International magazine］
  We previously reported that a low-protein diet caused animals to develop fatty liver containing a high level of triglycerides (TG), similar to the human nutritional disorder "kwashiorkor". To investigate the underlying mechanisms, we cultured hepatocytes in amino acid-sufficient or deficient medium. Surprisingly, the intracellular TG level was increased by amino acid deficiency without addition of any lipids or hormones, accompanied by enhanced lipid synthesis, indicating that hepatocytes themselves monitored the extracellular amino acid concentrations to induce lipid accumulation in a cell-autonomous manner. We then confirmed that a low-amino acid diet also resulted in the development of fatty liver, and supplementation of the low-amino acid diet with glutamic acid to compensate the loss of nitrogen source did not completely suppress the hepatic TG accumulation. Only a dietary arginine or threonine deficiency was sufficient to induce hepatic TG accumulation. However, supplementation of a low-amino acid diet with arginine or threonine failed to reverse it. In silico analysis succeeded in predicting liver TG level from the serum amino acid profile. Based on these results, we conclude that dietary amino acid composition dynamically affects the serum amino acid profile, which is sensed by hepatocytes and lipid synthesis was activated cell-autonomously, leading to hepatic steatosis.
  English, Scientific journal
  DOI：https://doi.org/10.1038/s41598-018-23640-8
  DOI ID：10.1038/s41598-018-23640-8, PubMed ID：29615653, PubMed Central ID：PMC5882898

• オルニチンが肝細胞の糖代謝遺伝子発現を制御する　　　　　　　　　　　　　　　
  西 宏起; 高橋 伸一郎; 伯野 史彦
  Volume：80, Number：2, First page：134, Last page：135, Mar. 2022
  Japanese
  ISSN：0914-8981, 医中誌Web ID：2022201092
• アミノ酸の新機能 血中プロファイルに応じた脂質代謝の変動　　　　　　　　　　　　　　　
  西 宏起; 伯野 史彦; 高橋 伸一郎
  Volume：76, Number：6, First page：467, Last page：471, Nov. 2018
  Japanese
  ISSN：0914-8981, 医中誌Web ID：2019066144

• 実験医学増刊 個人差の理解へ向かう肥満症研究 : GWAS、エピゲノム、腸内細菌、栄養学的知見から多様な病態を解明し、Precision Medicineをめざす
  梶村, 真吾; 小川, 佳宏; 矢作, 直也, [Contributor]
  Mar. 2021
  Japanese, Total pages：228p
  CiNii Books：http://ci.nii.ac.jp/ncid/BC06057803
  ISBN：9784758103930, CiNii Books ID：BC06057803
• 脂質・脂肪酸関連物質の使いこなし方 : 素材開発・機能創生・応用技術　　　　　　　　　　　　　　　
  石井, 淑夫, [Contributor]
  Sep. 2020
  Japanese, Total pages：3, 15, 592p
  CiNii Books：http://ci.nii.ac.jp/ncid/BC02781003
  ISBN：9784924728868, CiNii Books ID：BC02781003

• Apr. 2016 - Present
• Apr. 2016 - Present

• 低アルギニン食による脂肪肝誘導過程におけるオルニチンシグナルの寄与の解明　　　　　　　　　　　　　　　
  01 Apr. 2023 - 31 Mar. 2025
  Grant amount(Total)：4680000, Direct funding：3600000, Indirect funding：1080000
  Grant number：23K13923
• 生体の糖脂質代謝スイッチを誘導するオルニチン情報伝達経路の同定とその制御　　　　　　　　　　　　　　　
  01 Apr. 2022 - 31 Mar. 2025
  Grant amount(Total)：17420000, Direct funding：13400000, Indirect funding：4020000
  Grant number：23K23793
• Development of the system for diagnosis of unwellness and presentation of diet for improvement using a self-organizing map　　　　　　　　　　　　　　　
  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), 01 Apr. 2021 - 31 Mar. 2024
  Masuda Masato
  Grant amount(Total)：4030000, Direct funding：3100000, Indirect funding：930000
  In this study, we developed a system to diagnose unwellness from blood amino acid profiles using self-organizing maps, which is one of the artificial intelligence technologies. This system projects the input individual into a space that maps diseases and other factors when the blood amino acid profile is input, and can visualize the disease status and disease risk.Blood analysis can be performed annually for health checkups, etc., so that the individual's condition can be tracked over time, which can be used for disease protection and early detection.
  For the diet for improvement, the system uses machine learning to suggest the amino acid balance of the diet to improve the abnormal blood amino acid profile to the normal blood amino acid profile.
  Grant number：21K05485
• Identification of novel amino acid signaling pathways mediated by ornithine　　　　　　　　　　　　　　　
  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Early-Career Scientists, 01 Apr. 2021 - 31 Mar. 2023
  NISHI Hiroki, The University of Tokyo
  Grant amount(Total)：4550000, Direct funding：3500000, Indirect funding：1050000
  I have succeeded in generating the sufficient amount of ornithine-conjugated beads. Then, mixing them with the lysate of H4IIE rat hepatoma cells and analyzing the pulled-down proteins by LC-MS, I have succeeded in obtaining several proteins which specifically bind to ornithine. Experiments to define the physiological function of the obtained proteins in the amino acid signal transduction are currently in progress using H4IIE cells.
  Regarding the analyses on neutral lipid accumulation in Drosophila melanogaster that is fed a low-protein diet, the experimental reproducibility has suddenly become lower for unknown reason. Thus, I have been trying to overcome the problem and simultaneously to re-design the assay method.
  Grant number：21K14826
• アミノ酸欠乏をシグナルとした組織特異的な脂質代謝制御の新機構の解明とその利用　　　　　　　　　　　　　　　
  22 Apr. 2016 - 31 Mar. 2019
  Grant amount(Total)：1900000, Direct funding：1900000
  Grant number：16J08326