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Overnutrition and maternal obesity in sheep pregnancy alter the JNK-IRS-1 signaling cascades and cardiac function in the fetal heart.

ABSTRACT: Maternal obesity in pregnancy predisposes offspring to insulin resistance and associated cardiovascular disease. Here, we used a well-established sheep model to investigate the effects of maternal obesity on cardiac functions. Multiparous ewes were assigned to a control (CON) diet [100% of National Research Council (NRC) recommendations] or an obesogenic (OB) diet (150% of NRC recommendations) from 60 d before conception to necropsy on d 135 of pregnancy. Fetal blood glucose and insulin were increased (P<0.01, n=8) in OB (35.09+/-2.03 mg/dl and 3.40+/-1.43 microU/ml, respectively) vs. CON ewes (23.80+/-1.38 mg/dl and 0.769+/-0.256 microU/ml). Phosphorylation of AMP-activated protein kinase (AMPK), a cardioprotective signaling pathway, was reduced (P<0.05), while the stress signaling pathway, p38 MAPK, was up-regulated (P<0.05) in OB maternal and fetal hearts. Phosphorylation of c-Jun N-terminal kinase (JNK) and insulin receptor substrate-1 (IRS-1) at Ser-307 were increased (P<0.05) in OB fetal heart associated with lower downstream PI3K-Akt activity (P<0.05), indicating impaired cardiac insulin signaling. Although OB fetal hearts exhibited a normal contractile function vs. CON fetal hearts during basal perfusion, they developed an impaired heart-rate-left-ventricular-developed pressure product in response to high workload stress. Taken together, fetuses of OB mothers demonstrate alterations in cardiac PI3K-Akt, AMPK, and JNK-IRS-1 signaling pathways that would predispose them to insulin resistance and cardiac dysfunction.

SUBMITTER: Wang J

PROVIDER: S-EPMC2874473 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature

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Overnutrition and maternal obesity in sheep pregnancy alter the JNK-IRS-1 signaling cascades and cardiac function in the fetal heart.

Wang Jingying J Ma Heng H Tong Chao C Zhang Hanying H Lawlis Gavin B GB Li Yuanda Y Zang Mengwei M Ren Jun J Nijland Mark J MJ Ford Stephen P SP Nathanielsz Peter W PW Li Ji J

FASEB journal : official publication of the Federation of American Societies for Experimental Biology 20100128 6

Maternal obesity in pregnancy predisposes offspring to insulin resistance and associated cardiovascular disease. Here, we used a well-established sheep model to investigate the effects of maternal obesity on cardiac functions. Multiparous ewes were assigned to a control (CON) diet [100% of National Research Council (NRC) recommendations] or an obesogenic (OB) diet (150% of NRC recommendations) from 60 d before conception to necropsy on d 135 of pregnancy. Fetal blood glucose and insulin were inc ...[more]

PMID: 20110268

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Project description:PurposeTo evaluate the effects of the association between first trimester vitamin D (VitD) concentrations and increased prepregnancy body mass index (BMI) on early fetal growth restriction (FGR).MethodsThis retrospective cohort study included 15,651 women with singleton pregnancy who delivered at the International Peace Maternity and Child Health Hospital between January 2015 and November 2016. Women were classified in two groups based on their serum 25(OH)D vitamin levels status: VitD sufficient (SUFF) group and VitD insufficient or deficient (INSUFF/DEF). The cut-off point for VitD concentration was 50.00 nmol/L. Comparisons were made between women with normal prepregnancy body weight (BMI 18.5-23.9 kg/m2) and overweight and obese (OWO) women (BMI > 24.0 kg/m2). Early FGR was defined as first-trimester gestational age-adjusted crown-rump length (CRL) in the lowest 20th centile of the population. Multivariate logistic regression was used to evaluate the association between maternal serum 25(OH)D levels and prepregnancy BMI with first trimester CRL and early FGR.ResultsIn VitD INSUFF/DEF group, the first trimester CRL was decreased (P = 0.005), and the risk of early FGR was increased by 13% (95% CI 1.04-1.24, P = 0.004) compared to the VitD SUFF group. In OWO group, the first trimester CRL was also significantly decreased (P < 0.0001), and the risk of early FGR was significantly increased by 58% (95% CI 1.40-1.78, P < 0.001) compared with normal weight group. Furthermore, there was a significant combined effect of maternal VitD concentrations and OWO on CRL (P for interaction = 0.02) and the risk of early FGR (P for interaction = 0.07).ConclusionSufficient first trimester serum 25(OH)D concentration was a protective factor for early fetal growth, especially among OWO mothers. Chinese Clinical Trial Registry (Registration number: ChiCTR1900027447 with date of registration on November 13, 2019-retrospectively registered).

Dataset Information

Overnutrition and maternal obesity in sheep pregnancy alter the JNK-IRS-1 signaling cascades and cardiac function in the fetal heart.

Publications

Overnutrition and maternal obesity in sheep pregnancy alter the JNK-IRS-1 signaling cascades and cardiac function in the fetal heart.

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