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Maternal obesity is associated with the formation of small dense LDL and hypoadiponectinemia in the third trimester.

ABSTRACT: 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).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.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.Women were recruited at hospital antenatal appointments, and study visits were in a clinical research suite.Plasma concentrations of lipids, triglyceride-rich lipoproteins, lipoprotein lipase mass, estradiol, steroid hormone binding globulin, insulin, glucose, leptin, and adiponectin were determined.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).Maternal obesity is associated with an atherogenic LDL subfraction phenotype and may provide a mechanistic link to poor vascular function and adverse pregnancy outcome.

SUBMITTER: Meyer BJ

PROVIDER: S-EPMC3736085 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

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Maternal obesity is associated with the formation of small dense LDL and hypoadiponectinemia in the third trimester.

Meyer Barbara J BJ Stewart Frances M FM Brown Elizabeth A EA Cooney Josephine J Nilsson Solveig S Olivecrona Gunilla G Ramsay Jane E JE Griffin Bruce A BA Caslake Muriel J MJ Freeman Dilys J DJ

The Journal of clinical endocrinology and metabolism 20130121 2

<h4>Context</h4>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).<h4>Hypothesis</h4>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.<h4> ...[more]

PMID: 23337718

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Project description:BACKGROUND:It is well established that obesity is associated with dysregulation of the ratio between the two major adipokines leptin and adiponectin. Furthermore, it was recently reported that maternal obesity has a significant impact on placental development. Leptin and adiponectin are present at the fetal-maternal interface and are involved in the development of a functional placenta. However, less is known about leptin and adiponectin's involvement in the placental alterations described in obese women. Hence, the objective of the present study was to characterize the placental expression and DNA methylation of these two adipokine systems (ligands and receptors) in obese women. RESULTS:Biopsies were collected from the fetal and maternal sides of third-trimester placenta in obese and non-obese (control) women. In both groups, leptin levels were higher on the fetal side than the maternal side, suggesting that this cytokine has a pivotal role in fetal growth. Secondly, maternal obesity (in the absence of gestational diabetes) was associated with (i) elevated DNA methylation of the leptin promoter on fetal side only, (ii) hypomethylation of the adiponectin promoter on the maternal side only, (iii) significantly low levels of leptin receptor protein (albeit in the absence of differences in mRNA levels and promoter DNA methylation), (iv) significantly low levels of adiponectin receptor 1 mRNA expression on the maternal side only, and (v) elevated DNA methylation of the adiponectin receptor 2 promoter on the maternal side only. CONCLUSION:Our present results showed that maternal obesity is associated with the downregulation of both leptin/adiponectin systems in term placenta, and thus a loss of the beneficial effects of these two adipokines on placental development. Maternal obesity was also associated with epigenetic changes in leptin and adiponectin systems; this highlighted the molecular mechanisms involved in the placenta's adaptation to a harmful maternal environment.

Project description:IntroductionSome types of antenatal maternal psychological distress may be associated with reduced fetal growth and birthweight. A stress-mediated reduction in placental blood flow has been suggested as a mechanism. Previous studies have examined this using ultrasound-derived arterial resistance measures in the uterine (UtA) and umbilical (UA) arteries, with mixed conclusions. However, a reduction in placental volume blood flow may occur before changes in arterial resistance measures are seen. Fetoplacental volume blood flow can be quantified non-invasively in the umbilical vein (UV). Our objective was to study whether specific types of maternal psychological distress affect the placental circulation, using volume blood flow quantification in addition to arterial resistance measures.MethodsThis was a prospective observational study of 104 non-smoking pregnant women (gestational age 30 weeks) with uncomplicated obstetric histories. Psychological distress was measured by General Health Questionnaire-28 (subscales anxiety and depression) and Impact of Event Scale-22 (subscales intrusion, avoidance and arousal). UtA and UA resistance measures and UV volume blood flow normalized for fetal abdominal circumference, were obtained by Doppler ultrasound.ResultsIES intrusion scores above the mean were associated with a reduction in normalized UV volume blood flow (corresponding to -0.61 SD; P?=?0.003). Adjusting for UA resistance increased the strength of this association (difference -0.66 SD; P<0.001). Other distress types were not associated with UV volume blood flow. Maternal distress was not associated with arterial resistance measures, despite adjustment for confounders.ConclusionsIntrusive thoughts and emotional distress regarding the fetus were associated with reduced fetoplacental volume blood flow in third trimester. Uterine and umbilical artery resistance measures were not associated with maternal distress. Our findings support a decrease in fetoplacental blood flow as a possible pathway between maternal distress and reduced fetal growth.

Project description:BackgroundElevated triglyceride-rich lipoprotein (TRL) and small-dense low-density lipoprotein (sdLDL) particles are hallmarks of atherogenic dyslipidemia, and their cholesterol content is hypothesized to drive atherosclerotic risk. Prospective epidemiological data pertaining to cholesterol content of TRLs and sdLDL in primary prevention populations are mostly limited to coronary heart disease.ObjectivesThe purpose of this study was to prospectively evaluate whether triglyceride-rich lipoprotein cholesterol (TRL-C) and small-dense low-density lipoprotein cholesterol (sdLDL-C) concentrations associate with composite and individual incident cardiovascular disease (CVD) outcomes including myocardial infarction (MI), ischemic stroke (IS), and peripheral artery disease (PAD).MethodsIn a prospective case-cohort study within the Women's Health Study, TRL-C and sdLDL-C (mg/dl) were directly measured in baseline blood specimens of case subjects (n = 480) and the reference subcohort (n = 496). Risk associations were evaluated for total CVD (MI, IS, PAD, and CVD death), coronary and cerebrovascular disease (MI, IS, CVD death), and individual outcomes (MI, IS, and PAD). Models were adjusted for traditional risk factors, low-density lipoprotein cholesterol, and high-sensitivity C-reactive protein.ResultsThe risk of both composite outcomes significantly increased across quartiles of TRL-C and sdLDL-C. TRL-C was significantly associated with MI and PAD (MI hazard ratio [HR]Q4: 3.05 [95% confidence interval (CI): 1.46 to 6.39]; ptrend = 0.002; PAD HRQ4: 2.58 [95% CI: 1.18 to 5.63]; ptrend = 0.019), whereas sdLDL-C was significantly associated with MI alone (HRQ4: 3.71 [95% CI: 1.59 to 8.63]; ptrend < 0.001). Both markers weakly associated with IS. Association patterns were similar for continuous exposures and, for TRL-C, among subjects with low atherogenic particle concentrations (apolipoprotein B <100 mg/dl).ConclusionsTRL-C strongly associates with future MI and PAD events, whereas sdLDL-C strongly associates with MI alone. These findings signal that the cholesterol content of TRLs and sdLDL influence atherogenesis independently of low-density lipoprotein cholesterol, and high sensitivity C-reactive protein, with potentially different potency across vascular beds. (Women's Health Study; NCT00000479).

Project description:The obesity epidemic is a global challenge, and the velocity of propagation is high in the population at reproductive age. Overweight and obesity during pregnancy have been associated with high birth weight and an increased risk of childhood obesity, reinforcing the risk of other non-communicable diseases. Obesity involves chronic low-grade systemic inflammation. New biomarkers for early detection of obesity risk are urgently required. The aim of this study was to identify the connection between pregestational BMI (pre-BMI) status and inflammatory biomarkers during the third trimester of pregnancy and their association with intestinal microbiota composition. Fifty-four pregnant women were classified according to pre-pregnancy BMI as normoweight, overweight, or obese. Weight gain, inflammatory biomarkers (hs_CRP, haptoglobin, and suPAR), and microbiota composition were assessed during the third trimester. A significant lower weight gain for obese mothers and a positive correlation between pre-BMI and inflammatory biomarkers were detected (Spearman's correlation). Haptoglobin levels were significantly higher in overweight and obese mothers. Higher Firmicutes levels and a higher ratio Firmicutes/Bacteroidetes were observed in the overweight and obese subjects. High hs_CRP and haptoglobin levels were also correlated with decreased microbiota diversity (Shannon index), whereas haptoglobin and hs_CRP values were correlated with several microbiota components, such as Ruminococcus gnavus and Faecalibacterium, and with specific phyla in the normoweight and overweight mothers; no significant associations with microbiota were found for suPAR. In conclusion, haptoglobin and hs_CRP reflected pregestational BMI status and related microbiota components, but haptoglobin was a better biomarker for microbiota associated with overweight. suPAR was associated with low grade inflammation dependent on pre-pregnancy BMI, but it was not related to deviated microbiota profiles.

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Maternal obesity is associated with the formation of small dense LDL and hypoadiponectinemia in the third trimester.

Publications

Maternal obesity is associated with the formation of small dense LDL and hypoadiponectinemia in the third trimester.

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