2018 Fiscal Year Research-status Report
ホモカルノシンを骨格筋において増加させる新規手法およびその生理機能の探索
| Project/Area Number |
18K14407
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| Research Institution | Hiroshima University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Keywords | Homocarnosine / GABA / Skeletal muscle / Carnosine |
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| Outline of Annual Research Achievements |
We finished the first step of finding food factors enhancing endogenous homocarnosine synthesis in skeletal muscle. We found that dietary γ-aminobutyric acid (GABA) significantly increased homocarnosine levels (50-folds) in skeletal muscle. We hypothesized that GABA-degradating enzyme (GABA transaminase (GABA-T)) regulates intracellular GABA levels and affects the synthesis of homocarnosine in skeletal muscle. Thus, the enzyme inhibitor vig (Vig) was injected into mice. We found that Vig significantly inhibited GABA-T activity in liver and increased GABA and homocarnosine levels in skeletal muscle. Interestingly, Vig injection significantly increased GABA and homocarnosine levels in brain. For in vitro homocarnosine synthesis, the chemical synthesis protocol is already established.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
Currently, the research has progressed smoothly as planed. We could early establish the LC-MS method for detecting trace concentration of homocarnosine, which made the research progress smoothly. For producing large amount of homocarnosine for animal experiment in FY 2020, we struggled with over-expressing carnosine synthase in E.Coli. Thus, we changed to use the Fmoc solid-phase synthesis of homocarnosine instead and successfully established the protocol.
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| Strategy for Future Research Activity |
In FY 2019, synthesizing homocarnosine will be continued. Physiological effects of dietary GABA on skeletal muscle will be tested. GABA diet will be given to mice, then tibialis anterior (TA) muscle will be injured by injection of cardiotoxin. The effects of dietary GABA on muscle regeneration will be examined by histochemical and immunofluorescence analyses. Satellite cells or muscle stem cells will also be examined. This muscle regeneration experiment will be started from June, 2019.
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| Causes of Carryover |
Since we could find the potent food factor (GABA) inducing homocarnosine synthesis in skeletal muscle earlier than we thought, we could reduce a number of experiments. Thus, the usage of the budget was lower than planned. Instead of reducing a number of experiments in FY 2018, I have made up an additional experiment plan in FY 2019. In FY 2019, I will establish the mouse model for muscle regeneration to see if dietary GABA can help muscle to regenerate faster after damage. The establishment of this model is expected to cause much money on animals and cardiotoxin (an expensive chemical). Thus, the left amount of money (405,632 yen) will be used for the model establishment in this FY 2019.
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[Journal Article] GDE5 inhibition accumulates intracellular glycerophosphocholine and suppresses adipogenesis at a mitotic Clonal expansion stage2019
Author(s)
Okazaki Y, Nakamura K, Takeda S, Yoshizawa I, Yoshida F, Ohshima N, Izumi T, Klein JD, Kumrungsee T, Sands JM, Yanaka N.
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Journal Title
American Journal of Physiology-Cell Physiology
Volume: 316
Pages: C162-C174
DOI
Peer Reviewed
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[Journal Article] The effects of tempe fermented with Rhizopus microsporus, Rhizopus oryzae, or Rhizopus stolonifer on the colonic luminal environment in rats2018
Author(s)
Yang Y, Kameda T, Aoki H, Nirmagustina DE, Iwamoto A, Kato N, Yanaka N, Okazaki Y, and *Kumrungsee T
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Journal Title
Journal of Functional Foods
Volume: 49
Pages: 162-167
DOI
Peer Reviewed
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