第三章 筋特異的 BCAA 分解亢進マウスの運動適応性に対する BCAA 投与の影響
3.4. 考察
BDK-mKOマウスでは、BCAA代謝亢進により体内でのBCAA濃度が減少したことで、
トレーニングによる運動持久力の上昇を抑制することを第二章で述べた。この持久力上 昇の抑制は、BCAA不足か、またはBCAA代謝亢進に伴うエネルギー代謝の乱れのどち らに起因するかを解明するために、BCAAを摂取させて血漿BCAA濃度がほぼ回復した 条件で走運動持久力を測定した。その結果、2週間のトレーニング後では、Controlマウ
スよりもBDK-mKOマウスの持久力が上回った。すなわち、BDK-mKOマウスは十分な
BCAAが供給されれば、トレーニングに十分に適応する能力を有しており、むしろ筋特 異的BCAA分解亢進は走運動力をControlマウスよりも上昇することが判明した。第二 章において、BDK-mKOマウスでは骨格筋のグリコーゲン量およびacetyl-CoAレベルを 低下させたので、本研究のBCAA水を摂取させたマウスのそれらを測定したところ、
BCAAを摂取させることによりBDK-mKOマウスのそれらのレベルはコントロールマウ スのレベルに回復していた。以上の結果より、BCAA分解亢進は走持久力の阻害要因で はなく、十分なBCAAが供給されればむしろ走パフォーマンスを上昇することが明らか となった。
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Table 3.1. BCAA composition of the BCAA water
Table 3.2. Body and tissue weights of the control and BDK-mKO mice with BCAA supplementation.
Item Control BDK-mKO
(g)
Body weight 25.4 ± 0.5 26.2 ± 0.3 Tissue (g/100 g body weight) Skeletal muscle 0.57 ± 0.02 0.57 ± 0.01
Heart 0.48 ± 0.01 0.50 ± 0.01 Liver 4.12 ± 0.11 4.38 ± 0.11 Epididymal adipose
tissue 1.19 ± 0.11 1.35 ± 0.07
Values are means ± SEM (n = 7). Skeletal muscle is a mixture of soleus, gastrocnemius, and plantaris muscles of the left hind-limb. Epididymal adipose tissues from both sides of the body were collected from the mice and combined.
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Table 3.3. Plasma amino acid concentrations of the control and BDK-mKO mice with BCAA supplementation.
Amino acid Control BDK-mKO
(µM)
Alanine 355 ± 23 476 ± 33*
Arginine 67 ± 4 96 ± 9*
Asparagine 64 ± 5 86 ± 4*
Asparate 24 ± 2 33 ± 3*
Glutamine 636 ± 14 611 ± 19
Glutamate 31 ± 2 43 ± 4*
Methionine 40 ± 2 51 ± 2
Phenylalanine 67 ± 3 67 ± 2
Serine 119 ± 6 131 ± 5
Threonine 117 ± 8 150 ± 8*
Tryptophan 32 ± 2 49 ± 7*
Tyrosine 66 ± 2 82 ± 4*
*Significant difference vs. control mice (P<0.05).
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Figure 3.1. Intake of water and BCAA in control and BDK-mKO mice with BCAA supplementation
# Significant difference between control and BDK-mKO mice.
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Figure 3.2. Endurance capacity of control and BDK-mKO mice with BCAA supplementation
The distance ran to exhaustion before and after 2 weeks’ training with BCAA supplementation.
*Significant difference vs. control mice after training (P<0.05).
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Figure 3.3. Plasma BCAA concentrations of control and BDK-mKO mice with BCAA supplementation.
# Significant difference between control and BDK-mKO mice.
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Figure 3.4. Glycogen contents in skeletal muscle of control and BDK-mKO mice
with BCAA supplementation
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Figure 3.5. Acetyl-CoA concentration in skeletal muscle of control and BDK-mKO
mice with BCAA supplementation
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Figure 3.6. Citrate synthase (A) and cytochrome c oxidase (B) activities in skeletal
muscle of control and BDK-mKO mice with BCAA supplementation
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結論
以前の報告によって、運動中また運動後のBCAA補給は筋タンパク質合成の促進 と分解の抑制に繋がることが示唆されているので、BCAAは筋タンパク質を維持する ために重要と考えられる。本研究では、運動時における骨格筋のエネルギー代謝変動 に対するBCAA不足の影響について、以下のことを解明した。
BCKDCはBCAA分解の律速階段としてBDKにより制御されている。運動時には、
骨格筋でのBCKDCの脱リン酸化を活性化し、BCAAの酸化分解を高めて、BCAAが運 動時のエネルギーの一部を供給する。したがって、BCAAは運動持久力を向上する機能 があると考えられる。しかし、今回の実験で用いたBDK-mKOマウスでは、筋特異的に BDKがノックアウトされているので安静状態でもBCAA分解が亢進され、トレーニング による運動持久力の上昇を抑制したと推察された。この現象のメカニズムとしては、
BDK-mKOマウスにおいて、BCAA代謝の主な産物がacetyl-CoAではなくacyl-CARであ ったことと、BCAA不足に伴って一つのエネルギー源である筋グリコーゲンの蓄積量も 低下したことが考えられる。一方、BCAAサプリメント投与によりBCAA不足を解消す る研究では、acetyl-CoAと筋グリコーゲンの量も正常レベルまで回復されたと同時に、
BDK-mKOマウスの持久力がControlマウスのそれを上回った。これらの結果より、十
分なBCAA供給が運動トレーニングに対する適応に重要であることが示唆された。
本研究における運動と関係したBCAAの機能の所見は、筋肉におけるBCAA代謝 の調節機構の重要性を明らかにしたのみならず、運動による筋肥大、老化による筋萎 縮などにおけるBCAAの生理作用にも繋がる可能性があり、これらのBCAAの機能 を解明するためには更なる研究が必要である。
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