Decreased Concentrations of the Lipoprotein Lipase Inhibitor Angiopoietin-Like Protein 4 and Increased Serum Triacylglycerol Are Associated With Increased Neonatal Fat Mass in Pregnant Women With Gestational Diabetes Mellitus

Ortega-Senovilla, Henar; Schaefer-Graf, Ute M.; Meitzner, Katrin; Abou-Dakn, Michael; Herrera, Emilio

doi:10.1210/jc.2013-1614

Cited by 35 publications

(24 citation statements)

References 34 publications

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“…In these circumstances an additional stimulus may be required to induce the expression of ANGPTL4. This hypothesis is supported by our previous observation that neonates born by spontaneous delivery from pregnant women with gestational diabetes mellitus, with significantly higher concentrations in cord blood of cortisol (unpublished results), NEFAs and estimated insulin resistance (HOMA-IR) [47] than those found in neonates from control pregnant women, also showed a significantly higher concentration of ANGPTL4 in cord serum.…”

Section: Discussionsupporting

confidence: 77%

Lack of Relationship between Cord Serum Angiopoietin-Like Protein 4 (ANGPTL4) and Lipolytic Activity in Human Neonates Born by Spontaneous Delivery

et al. 2013

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BackgroundLigands of peroxisome-proliferator activated receptors (PPARs), such as non-esterified fatty acids (NEFAs), induce expression of angiopoietin-like protein 4 (ANGPTL4). Recently ANGPTL4 has been reported to be a mediator of intracellular adipose lipolysis induced by glucocorticoids.ObjectiveTo determine the concentrations of ANGPTL4 in cord serum of neonates born by spontaneous vaginal delivery (SVD) and by pre-labor cesarean section (CS) from healthy women, and to relate them to parameters of neonatal lipolytic activity at birth.MeasurementsIn 54 neonates born by SVD and in 56 neonates born by CS, arterial cord blood was drawn to determine insulin, cortisol, triacylglycerols (TAGs), glycerol, non-esterified fatty acids (NEFAs), individual fatty acids, ANGPTL4, adiponectin, retinol binding protein 4 (RBP4) and leptin.ResultsBirth weight and neonatal fat mass in SVD and CS showed no difference, but the concentrations of glycerol, adiponectin, RBP4, NEFAs and most individual fatty acids were higher in cord serum of neonates born by SVD compared to CS, indicating a higher adipose tissue breakdown in the SVD group. The concentrations of TAG and cortisol were also higher and that of insulin was lower in cord serum of SVD compared to the CS group. However, the concentration in cord serum of ANGPTL4 did not differ between the two groups and no positive correlation with either NEFA or glycerol concentrations were detected.ConclusionANGPTL4 is known to stimulate lipolysis in adults, but does not appear to mediate the increased activity in SVD, indicating the presence of different regulatory inputs.

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Section: Discussionsupporting

confidence: 77%

Lack of Relationship between Cord Serum Angiopoietin-Like Protein 4 (ANGPTL4) and Lipolytic Activity in Human Neonates Born by Spontaneous Delivery

et al. 2013

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“…Additionally, maternal obesity was associated with decreased angiopoietin-like protein 4 ( ANGPTL4 ), a potent inhibitor of LPL activity [22], suggesting that lower placental ANGPTL4 may promote lipid uptake via increased LPL activity. Furthermore, a recent study found ANGPL4 to be negatively associated with elevated circulating maternal lipids and increased neonatal adiposity [23], suggesting that it may influence the fetal environment. Although we did not observe a significant difference in birth weights of offspring born to lean and obese women, it remains possible that maternal obesity-associated changes to the placental environment resulted in programming of offspring metabolism, as previously observed in a rat model of maternal obesity-induced metabolic programming [24, 25].…”

Section: Discussionmentioning

confidence: 99%

Maternal obesity is associated with a lipotoxic placental environment

et al. 2014

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Maternal obesity is associated with placental lipotoxicity, oxidative stress, and inflammation, where MAPK activity may play a central role. Accordingly, we have previously shown that placenta from obese women have increased activation of MAPK-JNK. Here, we performed RNA-sequencing on term placenta from twenty-two subjects who were dichotomized based on pre-pregnancy BMI into lean (BMI 19–24 kg/m2; n = 12) and obese groups (BMI, 32–43 kg/m2; n = 12). RNA-seq revealed 288 genes to be significantly different in placenta from obese women by ≥1.4-fold. GO analysis identified genes related to lipid metabolism, angiogenesis, hormone activity, and cytokine activity to be altered in placenta from obese women. Indicative of a lipotoxic environment, increased placental lipid and CIDEA protein were associated with decreased AMPK and increased activation of NF-κB(p65) in placenta from obese women. Furthermore, we observed a 25% decrease in total antioxidant capacity and increased nuclear FOXO4 localization in placenta from obese women that was significantly associated with JNK activation, suggesting that maternal obesity may also be associated with increased oxidative stress in placenta. Maternal obesity was also associated with decreased HIF-1α protein expression, suggesting a potential link between increased inflammation/oxidative stress and decreased angiogenic factors. Together, these findings indicate that maternal obesity leads to a lipotoxic placental environment that is associated with decreased regulators of angiogenesis and increased markers of inflammation and oxidative stress.

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“…4 Although macrosomia has been associated with maternal blood glucose, 5,6 the results of previous studies are inconsistent. 7,8 Despite appropriate glycemic control in many pregnant women with GDM, macrosomia is still prevalent and is often linked to unrecognized maternal hyperglycemia. However, the risk of macrosomia is higher in well controlled GDM confirmed by continuous glucose monitoring (CGM) than the general population.…”

Section: Introductionmentioning

confidence: 99%

Level of maternal triglycerides is a predictor of fetal macrosomia in non-obese pregnant women with gestational diabetes mellitus

Hashemipour

Seidjavadi

Maleki

et al. 2018

Pediatrics & Neonatology

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Decreased Concentrations of the Lipoprotein Lipase Inhibitor Angiopoietin-Like Protein 4 and Increased Serum Triacylglycerol Are Associated With Increased Neonatal Fat Mass in Pregnant Women With Gestational Diabetes Mellitus

Cited by 35 publications

References 34 publications

Lack of Relationship between Cord Serum Angiopoietin-Like Protein 4 (ANGPTL4) and Lipolytic Activity in Human Neonates Born by Spontaneous Delivery

Lack of Relationship between Cord Serum Angiopoietin-Like Protein 4 (ANGPTL4) and Lipolytic Activity in Human Neonates Born by Spontaneous Delivery

Maternal obesity is associated with a lipotoxic placental environment

Level of maternal triglycerides is a predictor of fetal macrosomia in non-obese pregnant women with gestational diabetes mellitus

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