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.

中文翻译：

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维生素A通过p38 MAPK-PGC-1α信号通路调节线粒体生物发生和功能并改变绵羊的肌纤维组成

维生素 A (VA) 及其代谢物视黄酸 (RA) 因其广泛的生理功能而备受关注。然而，VA 对绵羊线粒体和肌纤维组成的调节作用尚未见报道。出生后第 2 天，将羔羊股二头肌注射 0（对照）或 7,500 IU VA 棕榈酸酯。在3周龄和32周龄时，获取背最长肌（LD）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。 VA处理的绵羊收获时LD肌肉中I型肌纤维的比例大大增加。 VA极大地促进了绵羊LD肌肉中线粒体的生物发生和功能。进一步探索发现，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，RA治疗后原代成肌细胞中I型肌纤维的数量显着增加，IIx型肌纤维的数量显着减少。与体内实验一致，RA显着改善了绵羊原代成肌细胞的线粒体生物合成和功能。然后，我们使用 si-PGC-1α 抑制 PGC-1α 表达，发现 si-PGC-1α 显着消除 RA 诱导的 I 型肌纤维的形成、线粒体生物发生、MitoTracker 染色强度、UQCRC1 和 ATP5A1 表达、SDH 活性和增强 IIx 型肌纤维的水平。这些数据表明，RA 通过促进 PGC-1α 表达和增加 I 型肌纤维来改善线粒体生物发生和功能。为了证明RA对PGC-1α水平的影响是由p38 MAPK信号引起的，我们使用p38 MAPK抑制剂抑制p38 MAPK信号，显着降低了RA诱导的PGC-1α和MyHC I水平。 VA通过p38 MAPK信号通路促进PGC-1α表达，改善线粒体生物合成，并改变肌纤维类型的组成。