Exploration of new methods to increase homocarnosine in skeletal muscle and their physiological functions

• Project/Area Number: 18K14407
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 38050:Food sciences-related
• Research Institution: Hiroshima University
• Principal Investigator: Kumrungsee Thanutchaporn 広島大学, 統合生命科学研究科(生), 准教授 (90781849)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: homocarnosine / GABA / skeletal muscle / muscle regeneration / satellite cell / sarcopenia / carnosine / Homocarnosine / Carnosine / Skeletal muscle / Muscle regeneration / Satellite cells

Outline of Final Research Achievements

This study showed that dietary GABA is a great strategy to induce endogenous homocarnosine synthesis in skeletal muscles. However, dietary GABA is highly fed into a degradation pathway rather than fed into the homocarnosine synthesis. Thus, high doses of GABA intake is required to increase muscular homocarnosine levels. To solve the problem, inhibitors of GABA degradation efficiently increased blood GABA levels and muscular homocarnosine levels. The findings suggest that dietary homocarnosine with GABA or GABA-degrading inhibitors may be a new method to enhance the efficiency of increasing imidazole peptides in the muscles. we found that homocarnosine and its analogs decrease satellite cell susceptibility to early cell death upon activation, suggesting positive effects of homocarnosine on muscle regeneration. This study provides a strong foundation for the research on new roles of homocarnosine and carnosine in muscle regeneration to build up healthy muscles and to prevent sarcopenia.

Academic Significance and Societal Importance of the Research Achievements

This study provides the new strategy to induce endogenous homocarnosine synthesis in the muscles and new mechanisms in regulating muscle regeneration. The findings will lead to the development of functional foods for building healthy muscles and preventing sarcopenia in both young and aging people.

Research Products

• [Journal Article] Dietary GABA and its combination with vigabatrin mimic calorie restriction and induce antiobesity-like effects in lean mice (2021)
  • Author(s): Sato K, Komaru T, Arima T, Jardson C, Yanaka N, Kumrungsee T
  • Journal Title: Journal of Functional Foods Volume: 78 Pages: 104367-104367
  • DOI: 10.1016/j.jff.2021.104367
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Liver choline metabolism and gene expression in choline-deficient mice offspring differ with gender (2021)
  • Author(s): Miyachi Y, Akiyama K, Tsukuda Y, Kumrungsee T, Yanaka N
  • Journal Title: Bioscience, Biotechnology, and Biochemistry Volume: 85 Issue: 2 Pages: 447-451
  • DOI: 10.1093/bbb/zbaa047
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Low-Dose Ethanol Has Impacts on Plasma Levels of Metabolites Relating to Chronic Disease Risk in SAMP8 mice (2020)
  • Author(s): Fu, C, Yang, Y, Kumrungsee, T, Kimoto, A, Izu, H, Kato, N
  • Journal Title: Journal of Nutritional Science and Vitaminology Volume: 66 Issue: 6 Pages: 553-560
  • DOI: 10.3177/jnsv.66.553
  • NAID: 130007964461
  • ISSN: 0301-4800, 1881-7742
  • Year and Date: 2020-12-31
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Potential Role of Vitamin B6 in Ameliorating the Severity of COVID-19 and Its Complications (2020)
  • Author(s): Kumrungsee T, Zhang P, Chartkul M, Yanaka N, Kato N.
  • Journal Title: Frontiers in nutrition Volume: 7
  • DOI: 10.3389/fnut.2020.562051
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Mungbean seed coat water extract inhibits inflammation in LPS-induced acute liver injury mice and LPS-stimulated RAW 246.7 macrophages via the inhibition of TAK1/IκBα/NF-κB (2020)
  • Author(s): Sae-Tan S, Kumrungsee T, Yanaka N.
  • Journal Title: Journal of food science and technology Volume: 57 Issue: 7 Pages: 2659-2668
  • DOI: 10.1007/s13197-020-04302-y
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Dietary GABA induces endogenous synthesis of a novel imidazole peptide homocarnosine in mouse skeletal muscles (2020)
  • Author(s): Kumrungsee Thanutchaporn、Arima Takeshi、Sato Kanako、Komaru Takumi、Sato Mikako、Oishi Yasuyuki、Egusa Ai、Yanaka Noriyuki
  • Journal Title: Amino Acids Volume: 52 Issue: 5 Pages: 743-753
  • DOI: 10.1007/s00726-020-02848-x
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Novel preventive mechanisms of vitamin B6 against inflammation, inflammasome, and chronic diseases (2020)
  • Author(s): Zhang P, Suda T, Kumrungsee T, Yanaka N, and Kato N
  • Journal Title: Molecular Nutrition of Vitamins Volume: - Pages: 283-299
  • DOI: 10.1016/b978-0-12-811907-5.00032-4
  • ISBN: 9780128119075
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] The serum amyloid A3 promoter-driven luciferase reporter mice is a valuable tool to image early renal fibrosis development and shows the therapeutic effect of glucosyl-hesperidin treatment (2019)
  • Author(s): Kumrungsee T, Kariya T, Hashimoto K, Koyano T, Yazawa N, Hashimoto T, Sanada Y, Matsuyama M, Sotomaru Y, Sakurai H, Van de Loo F.A.J, Yanaka N
  • Journal Title: Scientific Reports Volume: 9 Issue: 1 Pages: 14101-14101
  • DOI: 10.1038/s41598-019-50685-0
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Feeding Aspergillus protease preparation combined with adequate protein diet to rats increases levels of cecum gut-protective amino acids, partially linked to Bifidobacterium and Lactobacillus (2019)
  • Author(s): Yang Y, *Kumrungsee T, Kuroda M, Yamaguchi S, Kato N
  • Journal Title: Bioscience, Biotechnology, and Biochemistry Volume: 83 Issue: 10 Pages: 1901-11
  • DOI: 10.1080/09168451.2019.1627183
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Novel metabolic disturbances in marginal vitamin B 6 -deficient rat heart (2019)
  • Author(s): Kumrungsee T, Nirmagustina DE, Arima T, Onishi K, Sato K, Kato N, Yanaka N.
  • Journal Title: Journal of Nutritional Biochemistry Volume: 65 Pages: 26-34
  • DOI: 10.1016/j.jnutbio.2018.11.004
  • Peer Reviewed
• [Journal Article] GDE5 inhibition accumulates intracellular glycerophosphocholine and suppresses adipogenesis at a mitotic Clonal expansion stage (2019)
  • Author(s): Okazaki Y, Nakamura K, Takeda S, Yoshizawa I, Yoshida F, Ohshima N, Izumi T, Klein JD, Kumrungsee T, Sands JM, Yanaka N.
  • Journal Title: American Journal of Physiology-Cell Physiology Volume: 316 Issue: 2 Pages: C162-C174
  • DOI: 10.1152/ajpcell.00305.2018
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] High-dose D-glucosamine Consumption Increases Serum and Cecum Levels of Ammonia and Ethanol and Causes Bacterial Overgrowth in Rats (2019)
  • Author(s): Nirmagustina DE, Khedara A, Benouchenne D, Boubekri K, Yang Y, Suidasari S, *Kumrungsee T, and Kato N
  • Journal Title: Food Science and Technology Research Volume: 25 Issue: 1 Pages: 107-113
  • DOI: 10.3136/fstr.25.107
  • NAID: 130007606374
  • ISSN: 1344-6606, 1881-3984
  • Peer Reviewed
• [Journal Article] Gender Difference and Dietary Supplemental Vitamin B₆: Impact on Colon Luminal Environment (2018)
  • Author(s): Nirmagustina DE, Yang Y, Kumrungsee T, Yanaka N, Kato N.
  • Journal Title: Journal of Nutritional Science and Vitaminology Volume: 64 Issue: 2 Pages: 116-128
  • DOI: 10.3177/jnsv.64.116
  • NAID: 130006728835
  • ISSN: 0301-4800, 1881-7742
  • Peer Reviewed
• [Journal Article] The effects of tempe fermented with Rhizopus microsporus, Rhizopus oryzae, or Rhizopus stolonifer on the colonic luminal environment in rats (2018)
  • Author(s): Yang YS, Kameda T, Aoki H, Nirmagustina DE, Iwamoto A, Kato N, Yanaka N, Okazaki Y, Kumrungsee T.
  • Journal Title: J Funct Foods Volume: 49 Pages: 162-167
  • DOI: 10.1016/j.jff.2018.08.017
  • Peer Reviewed
• [Presentation] Vitamin B6 Regulates Muscle Satellite Cell Function: A Novel Possible Role of Vitamin B6 in Muscle Regeneration. (2020)
  • Author(s): Kumrungsee T, Onishi K, Komaru T, Yanaka N, Kato N.
  • Organizer: Nutrition 2020 (American Society of Nutrition)
  • Int'l Joint Research
• [Presentation] The potential roles of vitamin B6 in satellite cell functions (2020)
  • Author(s): Thanutchaporn Kumrungsee, Kai Onishi, Takumi Komaru, Noriyuki Yanaka
  • Organizer: 日本農芸化学会2020年度大会[福岡]
• [Presentation] Vitamin B6 deficiency impairs imidazole homeostasis and energy metabolism in rat heart (2018)
  • Author(s): Thanutchaporn Kumrungsee, Dwi Eva Nirmagustina, Noriyuki Yanaka, Norihisa Kato
  • Organizer: Nutrition 2018
  • Int'l Joint Research