富含亮氨酸的饮食对妊娠荷瘤大鼠胎盘蛋白质组学和代谢组学特征的影响

摘要(中文译文)

妊娠期癌症是一种脆弱的状况，母体在此过程中经历显著的分子变化，包括蛋白质组和代谢组水平的变化，并伴有胎盘和胎儿发育的损伤。蛋白质组学和代谢组学的交互分析可以阐明癌症与妊娠相关的复杂动态。亮氨酸参与蛋白质合成和代谢调节，可能减轻肿瘤诱导的损伤。我们研究了妊娠、癌症和亮氨酸补充之间复杂关系中的胎盘蛋白质组学和代谢组学特征。对四组妊娠小鼠的胎盘组织进行了探索性、非靶向的蛋白质组学（质谱）和代谢组学（核磁共振波谱）分析：对照组（PC）、Walker-256荷瘤组（PW）、亮氨酸组（PL）以及荷瘤并喂食富含亮氨酸饮食组（PWL）。对每组内的技术重复数据进行了统计比较。肿瘤影响了母体体重，但亮氨酸减轻了胎盘重量下降和胎儿吸收。亮氨酸补充恢复了参与核结构、细胞骨架和免疫反应的胎盘蛋白。肿瘤进展损害了与蛋白质折叠和染色体定位相关的通路，而亮氨酸调节了干扰素-γ和过氧化氢反应。PW组胎盘表现为腺苷、葡萄糖、谷氨酸和琥珀酸水平降低，乳酸、肌酸和组胺水平升高，而亮氨酸补充恢复了腺苷和吡哆醇水平并降低了乳酸水平。受影响的丙氨酸/天冬氨酸/谷氨酸代谢、嘌呤代谢、β-丙氨酸代谢和柠檬酸循环在亮氨酸治疗组（PWL）中趋于正常，该组主要调节嘌呤和丙氨酸/天冬氨酸/谷氨酸通路以及丙酮酸代谢。富含亮氨酸的饮食部分恢复了胎盘蛋白和代谢物水平，使受影响的通路向氨基酸生物合成和丙酮酸代谢方向转变，并最大限度地减少了对胎儿发育的影响。

Abstract

Cancer during pregnancy is a fragile scenario where the maternal body undergoes significant molecular changes, including at proteomic and metabolomic levels, with damage to placenta and fetal development. Proteomic and metabolomic interaction analyses can clarify the complex dynamics in cancer associated with pregnancy. Leucine is involved in protein synthesis and metabolic regulation and may attenuate tumor-induced damage. We investigated placental proteomic and metabolomic profiles in the complex relationships among pregnancy, cancer, and leucine supplementation. Exploratory, non-targeted proteomic (mass spectrometry) and metabolomic (NMR spectrometry) analyses were performed on the placenta tissue of four pregnant groups: control (PC), Walker-256 tumor-bearing (PW), leucine (PL), and tumor-bearing fed a leucine-rich diet (PWL). Statistical comparisons were performed on technical replicate data within each group. Tumor affected maternal weight, but leucine attenuated the decrease in placental weight and fetal resorption. Leucine supplementation restored the placental proteins involved in the nuclear structure, cytoskeleton, and immune response. Tumor evolution impaired pathways related to protein folding and chromosome localization, whereas leucine modulated interferon-gamma and hydrogen peroxide responses. PW placentas exhibited decreased adenosine, glucose, glutamate, and succinate, with enhanced lactate, creatine, and histamine levels, whereas leucine supplementation restored adenosine and pyridoxine and reduced lactate levels. The affected alanine/aspartate/glutamate and purine metabolism, beta-alanine metabolism, and the citrate cycle were minimized in leucine treatment (PWL), which mainly modulates purine and alanine/aspartate/glutamate pathways and pyruvate metabolism. A leucine-rich diet partially restored placental protein and metabolite levels, leading affected pathways to shift towards amino acid biosynthesis and pyruvate metabolism and minimizing effects on fetal development.

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