Maternal obesity programs mitochondrial and lipid metabolism gene expression in infant umbilical vein endothelial cells.

Maternal obesity programs mitochondrial and lipid metabolism gene expression in infant umbilical vein endothelial cells.
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DOI:
10.1038/ijo.2016.142
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发表时间:
2016-11
影响因子:
4.9
通讯作者:
Patti, M-E
Patti, M-E
中科院分区:
医学2区
文献类型:
--
作者:
Costa, S. M. R.;Isganaitis, E.;Matthews, T. J.;Hughes, K.;Daher, G.;Dreyfuss, J. M.;da Silva, G. A. P.;Patti, M-E

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母亲肥胖会增加儿童肥胖的风险,但分子机制尚不清楚。我们假设,超重和肥胖母亲的婴儿的原代脐静脉内皮细胞(HUVEC)会有反映后代肥胖风险的转录模式。在这项观察性队列研究中,我们招募了13名瘦(孕前体重指数为25.0 kg/m2)和24名超重肥胖(体重指数≥为25.0 kg/m2)女性。我们分离了原代HUVEC,并分析了基因表达(PrimeView、Affymetrix)和脐带血中激素和脂肪因子的水平。在超重肥胖母亲的婴儿中,142个转录本在HUVEC中差异表达(假发现率,FDR<0.05)。通径分析显示,参与线粒体和脂肪代谢的基因与母亲体重指数呈负相关(FDR<0.05)。为了测试这些转录模式是否与母亲肥胖背景下不同的营养暴露有关,我们分析了脐带血脂体,注意到总游离脂肪酸(瘦:95.5±37.1ug/ml,肥胖:124.1±46.0ug/ml,P=0.049)、棕榈酸(瘦:34.5±12.7ug/ml,肥胖:46.3±18.4ug/ml,P=0.03)和硬脂酸(瘦:20.8±8.2ug/ml,超重肥胖母亲的婴儿:29.7±17.2 ug/ml,P=0.04)。产前暴露于母体肥胖会改变HUVEC线粒体和脂类代谢相关基因的表达,潜在地反映了氧化和脂类代谢在发育过程中的差异。
Maternal obesity increases risk for childhood obesity, but molecular mechanisms are not well understood. We hypothesized that primary umbilical vein endothelial cells (HUVEC) from infants of overweight and obese mothers would harbor transcriptional patterns reflecting offspring obesity risk. In this observational cohort study, we recruited 13 lean (pre-pregnancy BMI <25.0 kg/m2) and 24 overweight-obese (‘ov-ob’, BMI ≥25.0 kg/m2) women. We isolated primary HUVEC, and analyzed both gene expression (Primeview, Affymetrix) and cord blood levels of hormones and adipokines. 142 transcripts were differentially expressed in HUVEC from infants of overweight-obese mothers (false discovery rate, FDR <0.05). Pathway analysis revealed that genes involved in mitochondrial and lipid metabolism were negatively correlated with maternal BMI (FDR <0.05). To test whether these transcriptomic patterns were associated with distinct nutrient exposures in the setting of maternal obesity, we analyzed the cord blood lipidome and noted significant increases in levels of total free fatty acids (lean: 95.5 ± 37.1 ug/ml, ov-ob: 124.1 ± 46.0 ug/ml, P=0.049), palmitate (lean: 34.5 ± 12.7 ug/ml, ov-ob: 46.3 ± 18.4 ug/ml, P=0.03) and stearate (lean: 20.8 ± 8.2 ug/ml, ov-ob: 29.7 ± 17.2 ug/ml, P=0.04), in infants of overweight-obese mothers. Prenatal exposure to maternal obesity alters HUVEC expression of genes involved in mitochondrial and lipid metabolism, potentially reflecting developmentally-programmed differences in oxidative and lipid metabolism.
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