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β-氨基异丁酸通过促进脂质分解代谢改善牛卵母细胞成熟及随后的胚胎发育。

Beta-aminoisobutyric acid improves bovine oocyte maturation and subsequent embryonic development by promoting lipid catabolism.

作者信息

Lu Canqiang, Li Zhengda, Xia Fan, Jia Ruru, Wang Yun, Bai Yuwei, Wei Chunye, Chen Yanyu, Lu Mingzhe, Shi Deshun, Lu Fenghua

机构信息

State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources, Guangxi Key Laboratory of Animal Breeding, Disease Control and Prevention, Guangxi University, Nanning, 530005, China.

Reproductive Medical and Genetic Center, The People's Hospital of Guangxi Zhuang Autonomous Region, Guangxi, Nanning, 530021, China.

出版信息

Theriogenology. 2025 Mar 1;234:153-163. doi: 10.1016/j.theriogenology.2024.12.016. Epub 2024 Dec 18.

Abstract

Energy metabolism homeostasis is essential for oocyte maturation and acquisition of developmental capacity. However, bovine oocyte in vitro maturation (IVM) is highly susceptible to metabolic stress and lipid accumulation. β-Aminoisobutyric acid (BAIBA), a metabolite produced in response to skeletal muscle exercise, has been reported to be involved in lipid and glucose metabolism, as well as inflammation and oxidative stress. This work aimed to evaluate the potential effects of BAIBA on bovine oocyte IVM and its mechanisms. Different concentrations of BAIBA (10, 20, 50, 100, and 200 μmol/L) were supplemented to bovine oocyte IVM medium. Results shown the BAIBA (50 μmol/L) had no effect on the extrusion rate of the first polar body of oocytes but significantly improved the subsequent blastocyst formation rate and embryo quality. Further revealed that supplementing BAIBA significantly up-regulated expression levels of genes to fatty acid β-oxidation metabolism (CPT1A, CPT1B and CPT2), promoted lipid metabolism, lowered lipid content, and improved mitochondrial membrane potential and active mitochondria content. Importantly, BAIBA stimulation significantly increased the phosphorylation of AMP-activated protein kinase (AMPK); and the inhibition of AMPK activity (Compound C, AMPK inhibitor) suppressed the ability of BAIBA to promote lipid metabolism in oocytes. Besides, inhibition of AMPK lowered the oocyte maturation rate and the subsequent zygote cleavage and blastocyst formation rate when compared to that of the BAIBA treatment. The results indicated that BAIBA was mainly involved in promoting lipid catabolism by activation of AMPK, consequently enhancing oocyte development potential.

摘要

能量代谢稳态对于卵母细胞成熟和发育能力的获得至关重要。然而,牛卵母细胞的体外成熟(IVM)极易受到代谢应激和脂质积累的影响。β-氨基异丁酸(BAIBA)是一种骨骼肌运动时产生的代谢物,据报道它参与脂质和葡萄糖代谢,以及炎症和氧化应激。本研究旨在评估BAIBA对牛卵母细胞IVM的潜在影响及其机制。在牛卵母细胞IVM培养基中添加不同浓度的BAIBA(10、20、50、100和200 μmol/L)。结果表明,50 μmol/L的BAIBA对卵母细胞第一极体的排出率没有影响,但显著提高了随后的囊胚形成率和胚胎质量。进一步研究表明,添加BAIBA显著上调了脂肪酸β-氧化代谢相关基因(CPT1A、CPT1B和CPT2)的表达水平,促进了脂质代谢,降低了脂质含量,并改善了线粒体膜电位和活性线粒体含量。重要的是,BAIBA刺激显著增加了AMP激活的蛋白激酶(AMPK)的磷酸化;抑制AMPK活性(化合物C,AMPK抑制剂)抑制了BAIBA促进卵母细胞脂质代谢的能力。此外,与BAIBA处理相比,抑制AMPK降低了卵母细胞成熟率以及随后的合子分裂和囊胚形成率。结果表明,BAIBA主要通过激活AMPK促进脂质分解代谢,从而增强卵母细胞的发育潜能。

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