{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T20:32:55Z","timestamp":1793046775443,"version":"4.5.0"},"reference-count":31,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T00:00:00Z","timestamp":1775606400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ausnutria Food and Nutrition Science Research Fund","award":["AU-YJY-B-LX-20-022"],"award-info":[{"award-number":["AU-YJY-B-LX-20-022"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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 PPAR\u03b1, Acox1, Acox3 and CPT1 in the liver tissues was analyzed using Quantitative reverse transcription-polymerase chain reaction (RT-qPCR) and Western Blot (WB).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>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 PPAR\u03b1, 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec005\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0346676","type":"journal-article","created":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T17:32:27Z","timestamp":1775669547000},"page":"e0346676","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Folic acid supplementation ameliorates long-term lipid metabolism following 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