生殖医学杂志2025，Vol.34Issue(6)：797-807,11.DOI:10.3969/j.issn.1004-3845.2025.06.011
妊娠期代谢综合征期间PPARγ通过调节ANGPTL4表达调控胎盘脂代谢
The effect of PPARγ in regulating placental lipid metabolism by modulating ANGPTL 4 expression during metabolic syndrome in pregnancy
摘要
Abstract
Objective:To investigate the effects of gestational metabolic syndrome(GMS)on placental lipid metabolism in the offspring,focusing on the analysis of fatty acid accumulation and its potential regulatory mechanisms in placental function. Methods:A GMS model was established in Wistar rats using a high-calorie diet combined with fructose water intake.Changes in metabolites and fatty acid contents in placental tissues were analyzed.Untargeted metabolomics,quantitative fatty acid metabolomics,and cellular experiments were employed to explore the effects of fatty acid accumulation on the lipid metabolism of trophoblast cells(HTR8-SVneo,JEG-3).The regulatory mechanisms of lipid metabolism were further investigated using peroxisome proliferator-activated receptor(PPARα/β/γ)inhibitors. Results:In the GMS model,untargeted metabolomics analysis revealed sex-specific differences in placental lipid metabolic profiles.In female offspring,the levels of 113 metabolites were significantly elevated(P＜0.05),while those of 73 were significantly reduced(P＜0.05).In male offspring,the levels of 90 metabolites were significantly elevated(P＜0.05),and those of 77 were significantly reduced(P＜0.05).The principal component analysis(PCA)analysis of 48 free fatty acids indicated group differences between GMS and control offspring without significant sex-specific trends.Cellular experiments showed that co-treatment with oleic acid(OA)and palmitic acid(PA)resulted in the accumulation of lipid droplets in HTR8-SVneo and JEG-3 cells,along with a significant increase in intracellular angiopoietin-like 4(ANGPTL4)protein expression level(P＜0.001).Inhibition of peroxisome proliferator-activated receptor(PPAR)γ significantly reduced intracellular ANGPTL4 protein expression level in trophoblast cells(P＜0.01),and significantly reduced lipid droplet accumulation in trophoblast cells induced by free fatty acids(P＜0.05). Conclusions:Placental lipid metabolism exhibited sex-specific differences during gestational metabolic syndrome,and PPARγ-mediated ANGPTL4 expression played a role in regulating fatty acid metabolism in both female and male offspring placenta.关键词
妊娠期代谢综合征/代谢组学/脂肪酸/过氧化物酶体增殖物激活受体(PPARγ)/血管生成素样蛋白4(ANGPTL4)Key words
Gestational metabolic syndrome/Metabolomics/Fatty acids/Peroxisome proliferator-activated receptor γ/Angiopoietin-like protein 4分类
临床医学引用本文复制引用
吕志远,姚灿灿,郝嘉伟,吴晓银,王建霖,徐祥波,陈西华,贺斌..妊娠期代谢综合征期间PPARγ通过调节ANGPTL4表达调控胎盘脂代谢[J].生殖医学杂志,2025,34(6):797-807,11.基金项目
中央院所基本科研业务费(2023GJZD0105) （2023GJZD0105）
