JP6158565B2 - 筋タンパク質合成シグナル増強剤 - Google Patents
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Description
(1)乳脂肪球皮膜とアミノ酸を組み合わせてなる筋タンパク質合成シグナル増強剤。
(2)乳脂肪球皮膜とアミノ酸を組み合わせてなる筋量増加剤。
(3)乳脂肪球皮膜とアミノ酸を組み合わせてなる筋萎縮抑制剤。
牛乳由来の乳脂肪球皮膜は、食経験が豊富であり、高純度かつ安価なものも市販されており、それらを用いるのが特に好ましい。例えば、メグレジャパン(株)「BSCP」、雪印乳業(株)「ミルクセラミドMC−5」、(株)ニュージーランドミルクプロダクツ「Phospholipid Concentrate」等が挙げられる。
また、乳脂肪球皮膜及びアミノ酸の組み合わせは、筋タンパク質合成シグナル増強剤、筋量増加剤又は筋萎縮抑制剤を製造するために使用することができる。
本発明において、「筋量増加」とは、筋肉量を増加させること意味し、筋量低下の抑制も含まれる。また、「筋萎縮」とは、筋蛋白質の分解速度が合成速度を上回ることにより、筋蛋白質が減少する、もしくは筋細胞が減少し、結果的に筋量が低下することをいい、長期間の安静臥床や骨折等によるギプス固定、或いは微小重力暴露によるもの(廃用性筋萎縮という)と筋萎縮性側策硬化症(ALS)等の疾病による進行性筋萎縮に大別される。さらに、加齢に伴っても筋萎縮と同様の症状が起きることがあり、これは加齢性筋減弱症(サルコペニア)と呼ばれている。したがって「筋萎縮の抑制」とは、不活動や加齢、疾病等による筋量の低下を抑制することをいう。
経口投与用製剤中のアミノ酸の含有量は、一般的に製剤全質量の0.05質量%以上、好ましくは0.2質量%以上であり、且つ30質量%以下、好ましくは10質量%以下である。また0.05〜30質量%、好ましくは0.2〜10質量%である。
当該食品飼料中のアミノ酸の含有量は、一般的に製剤全質量の0.05質量%以上、好ましくは0.2質量%以上であり、且つ30質量%以下、好ましくは10質量%以下である。また0.05〜30質量%、好ましくは0.2〜10質量%である。
投与又は摂取対象としては、それを必要としているヒト等であるが、例えば筋肉減弱症の患者や加齢性筋肉減弱症のヒト、それらの予備軍などが好適に挙げられる。
<1>乳脂肪球皮膜及びアミノ酸を組み合わせてなる筋タンパク質合成シグナル増強剤。
<2>乳脂肪球皮膜及びアミノ酸を組み合わせてなる筋量増加剤。
<3>乳脂肪球皮膜とアミノ酸を組み合わせてなる筋萎縮抑制剤。
<4>筋タンパク質合成シグナル増強剤を製造するための乳脂肪球皮膜及びアミノ酸の組み合わせの使用。
<5>筋量増加剤を製造するための乳脂肪球皮膜及びアミノ酸の組み合わせの使用。
<6>筋萎縮抑制剤を製造するための乳脂肪球皮膜及びアミノ酸の組み合わせの使用。
<7>筋タンパク質合成シグナル増強に使用するための乳脂肪球皮膜及びアミノ酸の組み合わせ。
<8>筋量増加に使用するための乳脂肪球皮膜及びアミノ酸の組み合わせ。
<9>筋萎縮抑制に使用するための乳脂肪球皮膜及びアミノ酸の組み合わせ。
<10>乳脂肪球皮膜及びアミノ酸の有効量を組み合わせて投与又は摂取することによる筋タンパク質合成シグナル増強方法。
<11>乳脂肪球皮膜及びアミノ酸の有効量を組み合わせて投与又は摂取することによる筋量増加方法。
<12>乳脂肪球皮膜及びアミノ酸の有効量を組み合わせて投与又は摂取することによる筋萎縮抑制方法。
<13>上記<1>〜<12>において、アミノ酸は必須アミノ酸である。
<14>上記<1>〜<12>において、アミノ酸は疎水性アミノ酸である。
<15>上記<1>〜<12>において、アミノ酸は分岐アミノ酸である。
<16>上記<1>〜<12>において、アミノ酸はロイシン、イソロイシン及びバリンから選ばれる分岐アミノ酸である。
<17>上記<1>〜<12>において、アミノ酸はロイシンである。
<18>上記<1>〜<12>において、乳脂肪球皮膜とアミノ酸の質量比が、1:0.05〜1:30である。
<19>上記<7>〜<9>において、使用は非治療的使用である。
<20>上記<10>〜<12>において、方法は非治療的方法である。
<21>上記<10>〜<12>において、投与又は摂取の対象は、それぞれ筋量増加を必要とする若しくは希望する動物又はヒト、筋萎縮抑制を必要とする若しくは希望する動物又はヒトである。
<22>上記<1>、<4>、<7>、<10>において、筋タンパク質合成シグナル増強は、好適にはp70S6キナーゼのリン酸化である。
1週間の予備飼育後、6週齢の雄性SDラットを6群{1)対照群、2)MGM(0.68 g/kg体重:L)投与群、3)MGM(1.35 g/kg体重:H)投与群、4)ロイシン(0.68 g/kg体重:L)投与群、5)ロイシン(1.35 g/kg体重:H)投与群、6)MGM(0.68 g/kg体重:L)+ロイシン(0.68 g/kg体重:L)投与群}に分け(各群n=6)、各群18時間の絶食を行った。絶食後、水(対照群)、水に溶解したMGM、或いはロイシン(上記量)を胃ゾンデにて経口投与し、自由飲水・絶食下で1時間飼育を継続した。1時間後、ヒフク筋を摘出し、ウェスタンブロットサンプルに供した。
Protease inhibitor cocktail set III(CALBIOCHEM)を添加したCelLytic(TM) MT Cell Lysis Reagent,For mammalian tissues(SIGMA)内で、凍結保存していたヒフク筋組織をホモジナイズし、遠心分離(12000rpm、4℃、10分)後、上清を回収した。各タンパク質濃度をBCA protein assay kit(PIERCE)にて測定し、全ての濃度を統一した。各サンプル20μgをSDS−PAGE(レディーゲル5−15% BioRad)にて分離後、Immun−Blot PVDF membrane For Protein Blotting(Bio−Rad)に転写した。作製したメンブレンを1%のBSA(Wako)にてブロッキングし、その後、表1に示す1次抗体と90分間反応させた。メンブレンを洗浄後、Anti−rabbit IgG,HRP−linked Antibody(Cell Signaling Technology)と60分間反応させ、再びメンブレンを洗浄後、ECL Prime Western Blotting Detection Reagent(GE Healthcare)にてS6Kタンパク質の検出を行った。活性化のシグナルは、p70S6キナーゼ(S6K)の活性化(リン酸化)を指標とし、S6Kの総タンパクおよびリン酸化型を認識する抗体を用い検出したバンドより、[リン酸化型量/総タンパク量]という値を求めて表現した。対照群との有意差検定は、student's t−testにより行った。
低濃度のMGMおよびロイシンの併用投与群で、相乗的なS6Kのリン酸化亢進が認められ、筋タンパク質合成促進が示唆された(図1)。
Claims (6)
- 乳脂肪球皮膜とロイシンを組み合わせてなる筋タンパク質合成シグナル増強剤。
- 乳脂肪球皮膜とロイシンを組み合わせてなる筋量増加剤。
- 乳脂肪球皮膜とロイシンを組み合わせてなる筋萎縮抑制剤。
- 乳脂肪球皮膜とロイシンを組み合わせてなる筋タンパク質合成シグナル増強用食品又は食品組成物。
- 乳脂肪球皮膜とロイシンを組み合わせてなる筋量増加用食品又は食品組成物。
- 乳脂肪球皮膜とロイシンを組み合わせてなる筋萎縮抑制用食品又は食品組成物。
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