Docohexaenoic acid improves the reduced umbilical vein relaxation observed in the offspring of pregnancies with maternal obesity

Abstract
Background and objectives: Maternal obesity (MO) is associated with increased risk of long term metabolic risk in the offspring (REF), probably involving mechanisms such as early programming of insulin resistance in fetal and neonatal tissues. On the other hand, exposure to the polyunsaturated acid Docohexaenoic acid (DHA) has been related with increased insulin response in multiple cell types. The aims of our study were to evaluate the in vitro effect of DHA on vascular response of umbilical vein to insulin, and the role of the intracellular inhibitory phosphorylation of the insulin receptor substrate-1. Methods: Umbilical cords from normal and MO pregnant woman attending to obstetrics service at the Clinical Hospital of Pontificia Universidad Catolica de Chile were obtained after informed consent. Isolated rings of umbilical vein were used to evaluate vasodilatation capacity by wire-myography, in absence or presence of insulin (10-10 to 10-6 uM, 0-20 min) and DHA (100 uM, 12 h). Primary cultures of human umbilical vein endothelial cells (HUVEC) were used to evaluated phosphorylated and total protein levels of IRS-1 in cells exposed or not to insulin (1 nM, 30 min), in absence or presence of DHA (100 uM, 12 h). 308 Ann Nutr Metab 2017;71(suppl 2):1–1433 Oral Abstracts Results: Insulin produces a significant vasodilation (20%) in umbilical vein rings from normal pregnancies, an effect that was absent in MO-derived umbilical rings. This vasodilator effect of insulin was recovered in umbilical vein rings from MO pregnancies pre-incubated with DHA. In addition, HUVEC from MO pregnancies showed increased levels of IRS-1 phosphorylated in serine307, compared with normal cells, a difference that was reduced by DHA, even in presence of insulin. Conclusions: In vitro addition of DHA recovers the reduced vascular response to insulin in umbilical vein from MO pregnancies, involving a reduction of the inhibitory phosphorylation of IRS in serine307.
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Keywords
Early programming, Insulin resistance, Maternal obesity, Docohexaenoic acid, Human umbilical vein
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