Obesity downregulates lipid metabolism genes in first trimester placenta.
Obesity downregulates lipid metabolism genes in first trimester placenta.
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DOI：
10.1038/s41598-022-24040-9
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发表时间：
2022-11-12
影响因子：
4.6
通讯作者：
中科院分区：
文献类型：
--
作者：
肥胖妇女胎盘的线粒体β-氧化脂肪酸(FA)水平较低，并在妊娠晚期积聚脂质。这会造成脂肪毒性的环境，损害胎盘的效率。我们假设妊娠早期肥胖的妇女胎盘FA代谢受损。我们评估了瘦身和肥胖妇女早期妊娠胎盘中FA代谢关键调节因子的表达。在手术时收集母体空腹甘油三酯和胰岛素水平。肥胖胎盘中与FA氧化相关的基因(FAO；ACOX1、CPT2、AMPKα)、FA摄取相关基因(LPL、LIPG、MFSD2A)、FA合成相关基因(ACACA)和储存相关基因(PLIN2)的表达均显著低于瘦弱女性。这种影响在男性胎儿的胎盘中加剧。肥胖妇女胎盘ACOX1蛋白水平较高，且与母体循环甘油三酯相关。PPARα途径丰富了受肥胖影响的胎盘基因，PPARα拮抗剂显著减少了妊娠早期胎盘组织中~3H-棕榈酸的氧化。这些结果表明，肥胖和高脂血症早在妊娠7周就会影响胎盘FA代谢。
Placentas of obese women have low mitochondrial β-oxidation of fatty acids (FA) and accumulate lipids in late pregnancy. This creates a lipotoxic environment, impairing placental efficiency. We hypothesized that placental FA metabolism is impaired in women with obesity from early pregnancy. We assessed expression of key regulators of FA metabolism in first trimester placentas of lean and obese women. Maternal fasting triglyceride and insulin levels were measured in plasma collected at the time of procedure. Expression of genes associated with FA oxidation (FAO; ACOX1, CPT2, AMPKα), FA uptake (LPL, LIPG, MFSD2A), FA synthesis (ACACA) and storage (PLIN2) were significantly reduced in placentas of obese compared to lean women. This effect was exacerbated in placentas of male fetuses. Placental ACOX1 protein was higher in women with obesity and correlated with maternal circulating triglycerides. The PPARα pathway was enriched for placental genes impacted by obesity, and PPARα antagonism significantly reduced 3H-palmitate oxidation in 1st trimester placental explants. These results demonstrate that obesity and hyperlipidemia impact placental FA metabolism as early as 7 weeks of pregnancy.
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影响因子：
3.8
作者：
Brass, E.;Hanson, E.;O'Tierney-Ginn, P. F.
通讯作者：
O'Tierney-Ginn, P. F.
影响因子：
2.7
作者：
Benjamini, Yoav;Krieger, Abba M.;Yekutieli, Daniel
通讯作者：
Yekutieli, Daniel
影响因子：
3.8
作者：
Hoch, Denise;Novakovic, Boris;Majali-Martinez, Alejandro
通讯作者：
Majali-Martinez, Alejandro
DOI：
10.1007/978-3-319-43589-3_4
发表时间：
2016-01-01
期刊：
AMP-ACTIVATED PROTEIN KINASE
影响因子：
--
作者：
Kaufman, Melissa R.;Brown, Thomas L.
通讯作者：
Brown, Thomas L.
影响因子：
4.9
作者：
Khaire, Amrita A.;Thakar, Shivani R.;Joshi, Sadhana R.
通讯作者：
Joshi, Sadhana R.