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亮氨酸通过蛋白激酶 B(Akt)/叉头框蛋白 1 信号通路和 microRNA-27a 促进猪肌纤维从快肌向慢肌转化。

Leucine promotes porcine myofibre type transformation from fast-twitch to slow-twitch through the protein kinase B (Akt)/forkhead box 1 signalling pathway and microRNA-27a.

机构信息

1Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education,Institute of Animal Nutrition,Sichuan Agricultural University,Chengdu,Sichuan 611130,People's Republic of China.

2College of Food Science,Sichuan Agricultural University,Yaan,Sichuan 625014,People's Republic of China.

出版信息

Br J Nutr. 2019 Jan;121(1):1-8. doi: 10.1017/S000711451800301X. Epub 2018 Nov 19.

DOI:10.1017/S000711451800301X
PMID:30449288
Abstract

Muscle fibre types can transform from slow-twitch (slow myosin heavy chain (MyHC)) to fast-twitch (fast MyHC) or vice versa. Leucine plays a vital effect in the development of skeletal muscle. However, the role of leucine in porcine myofibre type transformation and its mechanism are still unclear. In this study, effects of leucine and microRNA-27a (miR-27a) on the transformation of porcine myofibre type were investigated in vitro. We found that leucine increased slow MyHC protein level and decreased fast MyHC protein level, increased the levels of phospho-protein kinase B (Akt)/Akt and phospho-forkhead box 1 (FoxO1)/FoxO1 and decreased the FoxO1 protein level. However, blocking the Akt/FoxO1 signalling pathway by wortmannin attenuated the role of leucine in porcine myofibre type transformation. Over-expression of miR-27a decreased slow MyHC protein level and increased fast MyHC protein level, whereas inhibition of miR-27a had an opposite effect. We also found that expression of miR-27a was down-regulated following leucine treatment. Moreover, over-expression of miR-27a repressed transformation from fast MyHC to slow MyHC caused by leucine, suggesting that miR-27a is interdicted by leucine and then contributes to porcine muscle fibre type transformation. Our finding provided the first evidence that leucine promotes porcine myofibre type transformation from fast MyHC to slow MyHC via the Akt/FoxO1 signalling pathway and miR-27a.

摘要

肌纤维类型可以从慢肌(慢肌球蛋白重链(MyHC))转变为快肌(快 MyHC)或反之亦然。亮氨酸在骨骼肌的发育中起着至关重要的作用。然而,亮氨酸在猪肌纤维类型转化中的作用及其机制尚不清楚。在这项研究中,我们研究了亮氨酸和 microRNA-27a(miR-27a)对猪肌纤维类型转化的体外影响。我们发现亮氨酸增加了慢肌 MyHC 蛋白水平,降低了快肌 MyHC 蛋白水平,增加了磷酸化蛋白激酶 B(Akt)/Akt 和磷酸化叉头框蛋白 1(FoxO1)/FoxO1 的水平,并降低了 FoxO1 蛋白水平。然而,wortmannin 阻断 Akt/FoxO1 信号通路减弱了亮氨酸在猪肌纤维类型转化中的作用。miR-27a 的过表达降低了慢肌 MyHC 蛋白水平,增加了快肌 MyHC 蛋白水平,而 miR-27a 的抑制则产生相反的效果。我们还发现亮氨酸处理后 miR-27a 的表达下调。此外,miR-27a 的过表达抑制了亮氨酸引起的快肌 MyHC 向慢肌 MyHC 的转化,表明 miR-27a 被亮氨酸抑制,从而促进猪肌纤维类型转化。我们的研究结果首次证明,亮氨酸通过 Akt/FoxO1 信号通路和 miR-27a 促进猪肌纤维类型从快肌 MyHC 向慢肌 MyHC 的转化。

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