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Impact of maternal undernutrition around the time of conception on factors regulating hepatic lipid metabolism and microRNAs in singleton and twin fetuses.

ABSTRACT: We have investigated the effects of embryo number and maternal undernutrition imposed either around the time of conception or before implantation on hepatic lipid metabolism in the sheep fetus. We have demonstrated that periconceptional undernutrition and preimplantation undernutrition each resulted in decreased hepatic fatty acid ?-oxidation regulators, PGC-1? (P < 0.05), PDK2 (P < 0.01), and PDK4 (P < 0.01) mRNA expression in singleton and twin fetuses at 135-138 days gestation. In singletons, there was also lower hepatic PDK4 (P < 0.01), CPT-1 (P < 0.01), and PKC? (P < 0.01) protein abundance in the PCUN and PIUN groups and a lower protein abundance of PDPK-1 (P < 0.05) in the PCUN group. Interestingly, in twins, the hepatic protein abundance of p-AMPK (Ser(485)) (P < 0.01), p-PDPK-1 (Ser(41)) (P < 0.05), and PKC? (P < 0.05) was higher in the PCUN and PIUN groups, and hepatic PDK4 (P < 0.001) and CPT-1 (P < 0.05) protein abundance was also higher in the PIUN twin fetus. We also found that the expression of a number of microRNAs was altered in response to PCUN or PIUN and that there is evidence that these changes may underlie the changes in the protein abundance of key regulators of hepatic fatty acid ?-oxidation in the PCUN and PIUN groups. Therefore, embryo number and the timing of maternal undernutrition in early pregnancy have a differential impact on hepatic microRNA expression and on the factors that regulate hepatic fatty acid oxidation and lipid synthesis.

SUBMITTER: Lie S

PROVIDER: S-EPMC4719029 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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Impact of maternal undernutrition around the time of conception on factors regulating hepatic lipid metabolism and microRNAs in singleton and twin fetuses.

Lie Shervi S Morrison Janna L JL Williams-Wyss Olivia O Suter Catherine M CM Humphreys David T DT Ozanne Susan E SE Zhang Song S MacLaughlin Severence M SM Kleemann David O DO Walker Simon K SK Roberts Claire T CT McMillen I Caroline IC

American journal of physiology. Endocrinology and metabolism 20151020 2

We have investigated the effects of embryo number and maternal undernutrition imposed either around the time of conception or before implantation on hepatic lipid metabolism in the sheep fetus. We have demonstrated that periconceptional undernutrition and preimplantation undernutrition each resulted in decreased hepatic fatty acid β-oxidation regulators, PGC-1α (P < 0.05), PDK2 (P < 0.01), and PDK4 (P < 0.01) mRNA expression in singleton and twin fetuses at 135-138 days gestation. In singletons, ...[more]

PMID: 26487010

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Project description:To compare the rates of fetal growth restriction (FGR) in singleton and twin pregnancies using singleton and twin-specific birthweight standards. The study included liveborn twin and singleton pregnancies between January 2000 and January 2019. Hypertensive disorders of pregnancy (HDP) included gestational hypertension and pre-eclampsia. The study outcomes were FGR or small-for-gestational-age (SGA) at birth as assessed using singleton and twin reference charts. The analysis included 1473 twin and 62,432 singleton pregnancies. In singleton pregnancies the risk of PTB <34 weeks without HDP (OR 2.82, p < 0.001), delivery ≥34 weeks with HDP (OR 2.38, p < 0.001), and PTB <34 weeks with HDP (OR 13.65, p < 0.001) were significantly higher in the pregnancies complicated by FGR compared to those without. When selective fetal growth restriction (sFGR) was assessed using the singleton standard, the risk of PTB <34 weeks without HDP (OR 1.03, p = 0.872), delivery ≥34 weeks with HDP (OR 1.36, p = 0.160) were similar in the pregnancies complicated by sFGR compared to those without, while the risk of PTB <34 weeks with HDP (OR 2.41, p = 0.025) was significantly higher in the pregnancies complicated by sFGR compared to those without. When sFGR was assessed using the twin-specific chart, the risk of PTB <34 weeks without HDP (OR 3.55, p < 0.001), delivery ≥34 weeks with HDP (OR 3.17, p = 0.004), and PTB <34 weeks with HDP (OR 5.69, p < 0.001) were significantly higher in the pregnancies complicated by sFGR compared to those without. The stronger and more consistent association persisted in the subgroup analyses according to chorionicity. The strength of association in dichorionic twin pregnancies resembles that of the singletons more closely and consistently when the FGR was diagnosed using the twin-specific charts. FGR in twin pregnancies has a stronger and more consistent association with HDP and PTB when using twin-specific rather than singleton charts. This study provides further evidence supporting the use of twin-specific charts when assessing fetal growth in twin pregnancies.

Project description:IntroductionPrevention of cardiovascular disease and diabetes is a priority in low- and middle-income countries, especially in South Asia where these are leading causes of morbidity and mortality. The metabolic syndrome is a tool to identify cardiometabolic risk, but the validity of the metabolic syndrome as a clinical construct is debated. This study tested the existence of the metabolic syndrome, explored alternative cardiometabolic risk characterisations, and examined genetic and environmental factors in a South Asian population sample.MethodsData came from the Colombo Twin and Singleton follow-up Study, which recruited twins and singletons in Colombo, Sri Lanka, in 2012-2015 (n = 3476). Latent class analysis tested the clustering of metabolic syndrome indicators (waist circumference, high-density lipoprotein cholesterol, triglycerides, blood pressure, fasting plasma glucose, medications, and diabetes). Regression analyses tested cross-sectional associations between the identified latent cardiometabolic classes and sociodemographic covariates and health behaviours. Structural equation modelling estimated genetic and environmental contributions to cardiometabolic risk profiles. All analyses were stratified by sex (n = 1509 men, n = 1967 women).ResultsThree classes were identified in men: 1) "Healthy" (52.3%), 2) "Central obesity, high triglycerides, high fasting plasma glucose" (40.2%), and 3) "Central obesity, high triglycerides, diabetes" (7.6%). Four classes were identified in women: 1) "Healthy" (53.2%), 2) "Very high central obesity, low high-density lipoprotein cholesterol, raised fasting plasma glucose" (32.8%), 3) "Very high central obesity, diabetes" (7.2%) and 4) "Central obesity, hypertension, raised fasting plasma glucose" (6.8%). Older age in men and women, and high socioeconomic status in men, was associated with cardiometabolic risk classes, compared to the "Healthy" classes. In men, individual differences in cardiometabolic class membership were due to environmental effects. In women, genetic differences predicted class membership.ConclusionThe findings did not support the metabolic syndrome construct. Instead, distinct clinical profiles were identified for men and women, suggesting different aetiological pathways.

Dataset Information

Impact of maternal undernutrition around the time of conception on factors regulating hepatic lipid metabolism and microRNAs in singleton and twin fetuses.

Publications

Impact of maternal undernutrition around the time of conception on factors regulating hepatic lipid metabolism and microRNAs in singleton and twin fetuses.

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