Maternal Obesity Is Associated With the Formation of Small Dense LDL and Hypoadiponectinemia in the Third Trimester
ABSTRACT Context:Maternal obesity is associated with high plasma triglyceride, poor vascular function, and an increased risk for pregnancy complications. In normal-weight pregnant women, higher triglyceride is associated with increased small, dense low-density lipoprotein (LDL).Hypothesis:In obese pregnancy, increased plasma triglyceride concentrations result in triglyceride enrichment of very low-density lipoprotein-1 particles and formation of small dense LDL via lipoprotein lipase.Design:Women (n = 55) of body mass index of 18-46 kg/m(2) were sampled longitudinally at 12, 26, and 35 weeks' gestation and 4 months postnatally.Setting:Women were recruited at hospital antenatal appointments, and study visits were in a clinical research suite.Outcome Measures:Plasma concentrations of lipids, triglyceride-rich lipoproteins, lipoprotein lipase mass, estradiol, steroid hormone binding globulin, insulin, glucose, leptin, and adiponectin were determined.Results:Obese women commenced pregnancy with higher plasma triglyceride, reached the same maximum, and then returned to higher postnatal levels than normal-weight women. Estradiol response to pregnancy (trimester 1-3 incremental area under the curve) was positively associated with plasma triglyceride response (r(2) adjusted 25%, P < .001). In the third trimester, the proportion of small, dense LDL was 2-fold higher in obese women than normal-weight women [mean (SD) 40.7 (18.8) vs 21.9 (10.9)%, P = .014], and 35% of obese, 14% of overweight, and none of the normal-weight women displayed an atherogenic LDL subfraction phenotype. The small, dense LDL mass response to pregnancy was inversely associated with adiponectin response (17%, P = .013).Conclusions:Maternal obesity is associated with an atherogenic LDL subfraction phenotype and may provide a mechanistic link to poor vascular function and adverse pregnancy outcome.
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ABSTRACT: Aims OBJECTIVES: Low density lipoprotein (LDL)-cholesterol level in cord blood is approximately 30%. The aim or our study was to specifically explore LDL apoB distribution across sizes in cord blood serum. We studied 83 healthy neonates and 17 paired healthy mothers. Plasma glucose and serum lipids, such as low-density lipoprotein (LDL) cholesterol (LDL-C), HDL cholesterol (HDL-C) and triglycerides (TG), were measured using enzymatic methods. Distribution of apoB-100 was performed by western blot and immunodetection on native 4-12% polyacrylamide gels. LDL subclasses were analyzed by Lipoprint-LDL. Neonates show the expected lower content of apoB LDL and small dense LDL is the predominant apoB containing particle: 67±7%. However, only 1.5% is sdLDL by Lipoprint. Maternal serum contains a large proportion of apoB in smaller LDL, 47±6% as compared to non-pregnant women, 6±1%, p <0.001. Neonates show the expected lower content of apoB-LDL but an inverse distribution; sdLDL being the predominant particle. This novel finding for apoB sdLDL is consistent with previous data on HPLC studies showing increased middle and small-sized LDL lipid content in neonates as compared to adults which amount to 84% of total. Comparison of the results with Lipoprint LDL (lipids) with gradient gel electrophoresis native western blot (apoB-100) suggests that neonates carry fractions of small LDL that are comparatively poor in lipids as compared with their mothers. Further studies are warranted on the issue of sdLDL in neonates.Clinical biochemistry 12/2013; 47(6). DOI:10.1016/j.clinbiochem.2013.12.009 · 2.28 Impact Factor
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ABSTRACT: Maternal obesity and gestational diabetes mellitus (GDM) may independently influence offspring fat mass and metabolic disease susceptibility. In this pilot study, body composition and fat distribution in offspring from obese women with and without GDM and lean women were assessed within the 1st year of life, and maternal and newborn plasma factors were related to offspring adipose tissue distribution. Serum and plasma samples from pregnant obese women with (n = 16) or without (n = 13) GDM and normoglycemic lean women (n = 15) at 3rd trimester and offspring cord plasma were used for analyzing lipid profiles, insulin and adipokine levels. At week-1 and 6, month-4 and year-1, offspring anthropometrics and skinfold thickness (SFT) were measured and abdominal subcutaneous (SCA) and preperitoneal adipose tissue (PPA) were determined by ultrasonography. Cord insulin was significantly increased in the GDM group, whereas levels of cord leptin, total and high molecular weight (HMW) adiponectin were similar between the groups. Neonates of the GDM group showed significantly higher SFT and fat mass until week-6 and significantly increased SCA at week-1 compared to the lean group that persisted as strong trend at week-6. Interestingly, PPA in neonates of the GDM group was significantly elevated at week-1 compared to both the lean and obese group. At month-4 and year-1, significant differences in adipose tissue growth between the groups were not observed. Multiple linear regression analyses revealed that cord insulin levels are independently related to neonatal PPA that showed significant relation to PPA development at year-1. Maternal fasted C-peptide and HMW adiponectin levels at 3rd trimester emerged to be determinants for PPA at week-1. Maternal pregravid obesity combined with GDM leads to newborn hyperinsulinemia and increased offspring fat mass until week-6, whereas pregravid obesity without GDM does not. This strongly suggests the pivotal role of GDM in the adverse offspring outcome. Maternal C-peptide and HMW adiponectin levels in pregnancy emerge to be predictive for elevated PPA in newborns and might be indicative for the obesity risk at later life. Altogether, the findings from our pilot study warrant evaluation in long-term studies.Trial registration: German Clinical Trials Register DRKS00004370.BMC Pregnancy and Childbirth 04/2014; 14(1):138. DOI:10.1186/1471-2393-14-138 · 2.15 Impact Factor
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ABSTRACT: Context: Adiponectin (adpN) production is down-regulated in several situations associated with insulin resistance. The hypoadiponectinemia which develops in late pregnancy suggests a role of adpN in pregnancy-induced insulin resistance. Hypothesis: In obese pregnancy there is a decrease systemic adpN which result from downregulation of gene expression in adipose tissue. Design: One hundred and thirty-three women with uncomplicated pregnancies and a wide range in pre-gravid BMI (18-62 kg/m(2)) were recruited at term for a scheduled cesarean delivery. Maternal blood, placenta and subcutaneous abdominal adipose tissue were obtained in the fasting state. Outcome measures: DNA methylation was analyzed by MBD-based genome-wide methylation sequencing and methyl specific PCR of placenta and maternal adipose tissue. mRNA and protein expression were characterized by real time RT-PCR and immunodetection. Plasma adpN, leptin and insulin were assayed by ELISA. Results: Maternal adipose tissue was the prominent site of adpN gene expression with no detectable mRNA or protein in placenta. In obese women, adipose tissue adpN mRNA was significantly decreased (p< 0.01) whereas DNA methylation was significantly increased (p< 0.001) compared to lean women. The decreased adipose tissue expression resulted in normal weight women having significantly greater plasma adpN as compared with the severely obese (12.8±4.3 ng/ml vs. to 8.6 ±3.1, p<0.001). Plasma adpN was negatively correlated with maternal BMI (r=-0.28, p<0.001) and HOMA indices of insulin sensitivity (r=-0.32, p<0.001) but not with gestational weight gain. Conclusion: Maternal adipose tissue is the primary source of circulating adpN during pregnancy. Further, based on our results the placenta does not synthesize adiponectin at term. Obesity in pregnancy is associated with negative regulation of adpN adipose expression with increase in adpN DNA methylation associated to lower mRNA concentrations and hypoadiponectinemia. Maternal hypoadiponectinemia may have functional consequences in down-regulating biological signals transmitted by adpN receptors in various tissues, including the placenta.The Journal of Clinical Endocrinology and Metabolism 05/2014; 99(9):jc20134074. DOI:10.1210/jc.2013-4074 · 6.31 Impact Factor