Prenatal Choline Supplement in a Maternal Obesity Model Modulates Offspring Hepatic Lipidomes.
Prenatal Choline Supplement in a Maternal Obesity Model Modulates Offspring Hepatic Lipidomes.
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母亲妊娠期肥胖对子代健康造成不利影响，使其易患以胰岛素抵抗、常量营养素代谢失调和脂质过载为特征的慢性代谢性疾病，如代谢相关脂肪肝(MAFLD)。胆碱是一种参与脂肪和一碳代谢的半必需营养素，在MAFLD进展过程中受到损害。在这里，我们研究了在高脂(HF)肥胖喂养下，母体胆碱补充(CS)对小鼠后代肝脏脂类的影响。我们的结果表明，在胚胎17.5天和出生后6周，母体HF+CS增加了子代肝脏中一种称为血浆原的磷脂亚类的相对丰度。与血浆原作为牺牲性抗氧化剂的作用一致，HF+CS胚胎可能受到较低的氧化应激保护。出生后喂食HF的母体HF+CS雄性后代的鞘磷脂D42：2及其侧链神经酸(FA 24：1)的相对丰度也较高。神经酸只在过氧化酶体中代谢，并与血浆原合成有关。总之，本研究表明，在肥胖饮食的影响下，母体CS调节胎儿和雄性后代出生后的肝脏脂类，有利于血浆原的合成，这是一种抗氧化反应，可能保护小鼠肝脏免受HF喂养的损害。
Maternal obesity during pregnancy adversely impacts offspring health, predisposing them to chronic metabolic diseases characterized by insulin resistance, dysregulated macronutrient metabolism, and lipid overload, such as metabolic-associated fatty liver disease (MAFLD). Choline is a semi-essential nutrient involved in lipid and one-carbon metabolism that is compromised during MAFLD progression. Here, we investigated under high-fat (HF) obesogenic feeding how maternal choline supplementation (CS) influenced the hepatic lipidome of mouse offspring. Our results demonstrate that maternal HF+CS increased relative abundance of a subclass of phospholipids called plasmalogens in the offspring liver at both embryonic day 17.5 and after 6 weeks of postnatal HF feeding. Consistent with the role of plasmalogens as sacrificial antioxidants, HF+CS embryos were presumably protected with lower oxidative stress. After postnatal HF feeding, the maternal HF+CS male offspring also had higher relative abundance of both sphingomyelin d42:2 and its side chain, nervonic acid (FA 24:1). Nervonic acid is exclusively metabolized in the peroxisome and is tied to plasmalogen synthesis. Altogether, this study demonstrates that under the influence of obesogenic diet, maternal CS modulates the fetal and postnatal hepatic lipidome of male offspring, favoring plasmalogen synthesis, an antioxidative response that may protect the mouse liver from damages due to HF feeding.