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Background This study emphasizes the potential of folic acid (FA) supplementation in controlling intrauterine growth retardation (IUGR)-induced metabolic problems and improving the long-term health consequences of afflicted individuals. Objectives This study investigates the effect of IUGR on long-term lipid metabolism in the liver, and the role of early-life FA supplementation on IUGR-induced metabolic dysfunctions. We aim to provide novel insights for early interventions to prevent the development of lipid metabolism abnormalities in adulthood. Methods The IUGR model was induced by feeding pregnant rats a 10% low protein diet. After birth, lactating mothers were provided with a 21% normal protein diet. Offspring were initially breastfed and assigned to either an FA-supplemented diet or a standard diet without FA. Serum levels of total free fatty acids and triglycerides were measured by ELISA. Liver tissues were harvested for Hematoxylin and eosin (HE) to observe the liver structure. The expression of PPARα, Acox1, Acox3 and CPT1 in the liver tissues was analyzed using Quantitative reverse transcription-polymerase chain reaction (RT-qPCR) and Western Blot (WB). Results Levels of serum triglycerides (TG) and free fatty acids (FFA) were significantly higher in IUGR rats compared to control rats from the early stages and remained elevated through to 90 days of age. The HE results displayed an irregular arrangement of hepatocytes at birth in IUGR rats, and hepatocellular vacuoles by 90 days of age in the IUGR rats. The level of lipid-related genes was significantly low in the IUGR group, including PPARα, Acox1, Acox3 and CPT1. Early postnatal folic acid supplementation significantly decreased serum levels of TG and FFA, ameliorated the pathological changes in the livers and reversed the expression of lipid-related genes. Conclusions IUGR individuals are predisposed to lipid metabolism abnormalities in adulthood, which can be ameliorated by postnatal supplementation of FA, potentially serving as a therapeutic method.研究背景 本研究阐明了叶酸（folic acid, FA）补充在控制宫内生长受限（intrauterine growth retardation, IUGR）诱导的代谢异常，以及改善受累个体远期健康结局方面的潜力。 研究目的 本研究探讨宫内生长受限对肝脏长期脂质代谢的影响，以及早期叶酸补充对宫内生长受限诱导的代谢功能紊乱的调控作用，旨在为早期干预以预防成年期脂质代谢异常提供新的理论依据。 研究方法 本研究通过给妊娠大鼠饲喂10%低蛋白日粮构建宫内生长受限模型。仔鼠出生后，为泌乳母鼠提供21%正常蛋白日粮。子代仔鼠最初以母乳喂养，随后被随机分为叶酸补充日粮组与不含叶酸的标准日粮组。采用酶联免疫吸附测定（enzyme-linked immunosorbent assay, ELISA）检测血清总游离脂肪酸与甘油三酯（triglycerides, TG）水平；采集肝组织进行苏木精-伊红（hematoxylin and eosin, HE）染色，以观察肝脏组织结构；采用实时荧光定量反转录聚合酶链反应（quantitative reverse transcription-polymerase chain reaction, RT-qPCR）与蛋白质免疫印迹（western blot, WB）分析肝组织中过氧化物酶体增殖物激活受体α（PPARα）、酰基辅酶A氧化酶1（Acox1）、酰基辅酶A氧化酶3（Acox3）及肉碱棕榈酰转移酶1（CPT1）的表达水平。 研究结果 与对照组大鼠相比，宫内生长受限模型大鼠的血清甘油三酯（TG）与游离脂肪酸（FFA）水平从早期即显著升高，并持续至90日龄。苏木精-伊红染色结果显示，宫内生长受限模型大鼠出生时肝细胞排列紊乱，至90日龄时出现肝细胞空泡变性；宫内生长受限模型组大鼠的脂质相关基因（包括PPARα、Acox1、Acox3及CPT1）表达水平显著降低。出生后早期叶酸补充可显著降低血清TG与FFA水平，改善肝脏病理损伤，并逆转脂质相关基因的表达异常。 研究结论 宫内生长受限个体成年后易发生脂质代谢异常，而出生后叶酸补充可改善该状况，有望成为一种治疗手段。