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

ABSTRACT: 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 body mass index (BMI) <25.0?kg?m-2) and 24 overweight-obese ('ov-ob', BMI?25.0?kg?m-2) women. We isolated primary HUVEC, and analyzed both gene expression (Primeview, Affymetrix) and cord blood levels of hormones and adipokines.A total of 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 the levels of total free fatty acids (lean: 95.5±37.1??g?ml-1, ov-ob: 124.1±46.0??g?ml-1, P=0.049), palmitate (lean: 34.5±12.7??g?ml-1, ov-ob: 46.3±18.4??g?ml-1, P=0.03) and stearate (lean: 20.8±8.2??g?ml-1, ov-ob: 29.7±17.2??g?ml-1, 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.

SUBMITTER: Costa SM

PROVIDER: S-EPMC5101152 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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

Costa S M R SM Isganaitis E E Matthews T J TJ Hughes K K Daher G G Dreyfuss J M JM da Silva G A P GA Patti M-E ME

International journal of obesity (2005) 20160817 11

<h4>Background/objectives</h4>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.<h4>Subjects/methods</h4>In this observational cohort study, we recruited 13 lean (pre-pregnancy body mass index (BMI) <25.0 kg m<sup>-2</sup>) and 24 overweight-obese ('ov-ob', ...[more]

PMID: 27531045

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Project description:BackgroundExposure to diabetes in utero influences future metabolic health of the offspring. MicroRNAs (miRNA) are small noncoding RNAs that may contribute mechanistically to the effects on offspring imparted by diabetes mellitus (DM) during pregnancy. We hypothesized that exposure to DM during pregnancy influences select miRNAs in fetal circulation, in human umbilical vein endothelial cells (HUVEC), and placenta.MethodsmiRNA abundance was quantified using real-time PCR from RNA isolated from umbilical cord serum exosomes, HUVEC, and placenta exposed to diabetes or normoglycemia during pregnancy. The abundance of each of these miRNAs was determined by comparison to a known standard and the relative expression assessed using the 2-ΔΔCt method. Multivariable regression models examined the associations between exposure to diabetes during pregnancy and miRNA expression.ResultsmiR-126-3p was highly abundant in fetal circulation, HUVEC, and placenta. Diabetes exposure during pregnancy resulted in lower expression of miR-148a-3p and miR-29a-3p in the HUVEC. In the placenta, for miR-126-3p, there was a differential effect of DM by birth weight between DM versus control group, expression being lower at the lower birth weight, however not different at the higher birth weight.ConclusionExposure to DM during pregnancy alters miRNA expression in the offspring in a tissue-specific manner.ImpactmiRNAs are differentially expressed in fetal tissues from offspring exposed to in utero diabetes mellitus compared to those who were not exposed. miRNA expression differs among tissue types (human umbilical vein endothelial cells, placenta and circulation exosomes) and response to diabetes exposure varies according to tissue of origin. miRNA expression is also affected by maternal and infant characteristics such as infant birth weight, infant sex, maternal age, and maternal BMI. miRNAs might be one of the potential mechanisms by which offspring's future metabolic status may be influenced by maternal diabetes mellitus.

Project description:Background/aimsOxidative stress-induced damage in endothelial cells is a crucial initiator of atherosclerosis (AS), which is highly related to excessive reactive oxygen species (ROS) and mitochondrial dynamics. Resveratrol (RSV) exerts beneficial effects against endothelial oxidative injury, while the underlying mechanisms have not been fully elucidated. Thus, we aimed to explore the role of mitochondria dynamics during the anti-oxidative activities of RSV in palmitic acid (PA)-stimulated human umbilical vein endothelial cells (HUVECs) and to verify whether tyrosyl transfer- RNA synthetase (TyrRS) and poly (ADP-ribose) polymerase 1 (PARP1) are targeted during this process.MethodsHUVECs were exposed to 200 μM of PA for 16 h before treated with 10 μM of RSV for 8 h. Cell viability was detected using Cell counting kit-8 (CCK-8) assay. The intracellular ROS level and mitochondria membrane potential (MMP) were measured using microplate reader and flow cytometry. The malondialdehyde and superoxide dismutase were measured using the microplate reader. The mitochondrial morphology and fusion process was observed under transmission electron microscopy and confocal microscopy. TyrRS and PARP1 were knocked down with the specific small interference RNAs (siRNA), and the protein expressions of TyrRS, PARP1, and mitochondrial fusion proteins (MFN1, MFN2, and OPA1) were measured by western blot.ResultsRSV treatment suppressed the PA-induced injuries in HUVECs, including the damage to cell viability, oxidative stress, and loss of MMP. Additionally, RSV improved the protein levels of MFN1, MFN2, and OPA1 as well as inhibited the PA-induced fragmentation of mitochondria. However, the effects of RSV on oxidative stress and mitochondrial fusion were abolished by the pretreatment of siRNAs of TyrRS and PARP1, indicating that these effects of RSV were dependent on the TyrRS-PARP1 pathway.ConclusionsRSV attenuated endothelial oxidative injury by regulating mitochondrial fusion via TyrRS-PARP1 signaling pathway.

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

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

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