Vitamin A regulates mitochondrial biogenesis and function through p38 MAPK-PGC-1α signaling pathway and alters the muscle fiber composition of sheep

IF 7 1区 农林科学 Q1 Agricultural and Biological Sciences
Pengkang Song, Jiamin Zhao, Fanqinyu Li, Xiaoyi Zhao, Jinxin Feng, Yuan Su, Bo Wang, Junxing Zhao
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引用次数: 0

Abstract

Vitamin A (VA) and its metabolite, retinoic acid (RA), are of great interest for their wide range of physiological functions. However, the regulatory contribution of VA to mitochondrial and muscle fiber composition in sheep has not been reported. Lambs were injected with 0 (control) or 7,500 IU VA palmitate into the biceps femoris muscle on d 2 after birth. At the age of 3 and 32 weeks, longissimus dorsi (LD) muscle samples were obtained to explore the effect of VA on myofiber type composition. In vitro, we investigated the effects of RA on myofiber type composition and intrinsic mechanisms. The proportion of type I myofiber was greatly increased in VA-treated sheep in LD muscle at harvest. VA greatly promoted mitochondrial biogenesis and function in LD muscle of sheep. Further exploration revealed that VA elevated PGC-1α mRNA and protein contents, and enhanced the level of p38 MAPK phosphorylation in LD muscle of sheep. In addition, the number of type I myofibers with RA treatment was significantly increased, and type IIx myofibers was significantly decreased in primary myoblasts. Consistent with in vivo experiment, RA significantly improved mitochondrial biogenesis and function in primary myoblasts of sheep. We then used si-PGC-1α to inhibit PGC-1α expression and found that si-PGC-1α significantly abrogated RA-induced the formation of type I myofibers, mitochondrial biogenesis, MitoTracker staining intensity, UQCRC1 and ATP5A1 expression, SDH activity, and enhanced the level of type IIx muscle fibers. These data suggested that RA improved mitochondrial biogenesis and function by promoting PGC-1α expression, and increased type I myofibers. In order to prove that the effect of RA on the level of PGC-1α is caused by p38 MAPK signaling, we inhibited the p38 MAPK signaling using a p38 MAPK inhibitor, which significantly reduced RA-induced PGC-1α and MyHC I levels. VA promoted PGC-1α expression through the p38 MAPK signaling pathway, improved mitochondrial biogenesis, and altered the composition of muscle fiber type.
维生素 A 通过 p38 MAPK-PGC-1α 信号通路调节线粒体的生物生成和功能,并改变绵羊的肌肉纤维组成
维生素 A(VA)及其代谢产物视黄酸(RA)因其广泛的生理功能而备受关注。然而,VA 对绵羊线粒体和肌肉纤维组成的调节作用尚未见报道。在羔羊出生后第 2 天,向其股二头肌注射 0(对照组)或 7,500 IU VA 棕榈酸酯。在 3 周龄和 32 周龄时,采集背阔肌(LD)的肌肉样本,以探讨 VA 对肌纤维类型组成的影响。在体外,我们研究了RA对肌纤维类型组成和内在机制的影响。经 VA 处理的绵羊 LD 肌肉在收获时 I 型肌纤维的比例大大增加。VA极大地促进了绵羊LD肌肉线粒体的生物生成和功能。进一步研究发现,VA 提高了绵羊 LD 肌肉中 PGC-1α mRNA 和蛋白含量,并增强了 p38 MAPK 磷酸化水平。此外,在原代肌母细胞中,经 RA 处理的 I 型肌纤维数量明显增加,而 IIx 型肌纤维数量明显减少。与体内实验一致,RA 能明显改善绵羊原代肌母细胞的线粒体生物发生和功能。然后,我们用 si-PGC-1α 抑制 PGC-1α 的表达,发现 si-PGC-1α 能明显降低 RA 诱导的 I 型肌纤维形成、线粒体生物生成、MitoTracker 染色强度、UQCRC1 和 ATP5A1 表达、SDH 活性,并提高 IIx 型肌纤维的水平。这些数据表明,RA 通过促进 PGC-1α 的表达,改善了线粒体的生物生成和功能,并增加了 I 型肌纤维。为了证明RA对PGC-1α水平的影响是由p38 MAPK信号转导引起的,我们使用p38 MAPK抑制剂抑制了p38 MAPK信号转导,从而显著降低了RA诱导的PGC-1α和MyHC I水平。VA通过p38 MAPK信号通路促进了PGC-1α的表达,改善了线粒体的生物生成,并改变了肌肉纤维类型的组成。
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来源期刊
Journal of Animal Science and Biotechnology
Journal of Animal Science and Biotechnology AGRICULTURE, DAIRY & ANIMAL SCIENCE-
CiteScore
9.90
自引率
2.90%
发文量
822
审稿时长
17 weeks
期刊介绍: Journal of Animal Science and Biotechnology is an open access, peer-reviewed journal that encompasses all aspects of animal science and biotechnology. That includes domestic animal production, animal genetics and breeding, animal reproduction and physiology, animal nutrition and biochemistry, feed processing technology and bioevaluation, animal biotechnology, and meat science.
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