Maternal obesity and neonatal insulin resistance in the origin of metabolic syndrome in childhood

Abstract
Obesity during pregnancy has been recognized as an independent risk factor for maternal and fetal complications, including congenital anomalies, gestational diabetes mellitus, gestational hypertension and preeclampsia, caesarean delivery, macrosomia (birth weight > 4000 g), increased neonatal adiposity and hyperinsulinemia. In addition to perinatal complications associated to maternal obesity, rising epidemiological evidence has suggested the intrauterine programming of whole body insulin resistance (IR) in the offspring of obese pregnant woman, evaluated both at early neonatal stage and at young adulthood. Our cohort data showed association among elevated neonatal anthropometry measurements (birth weight and height) and increased levels of waist circumpherence and blood pressure in childohood, two components of the metabolic syndrome (MetS). In the other hand, the homeostasis model assesment index of insulin resistance (HOMA-IR) was correlated to the number of MetS components in this population. In order to describe potential mechanisms of relationship between maternal obesity and future development of MetS, we have evaluated modulators of neonatal insulin signaling pathway in human and animal models of maternal obesity. We have found increased levels of neonatal insulin secretion (serum C-peptide) and sub-clinical markers of cellular insulin resistance and endoplasmic reticulum stress (ER-stress) in offsprings of women with maternal weight excess. The ER stress response has been related to IR and diabetes mellitus development in multiple models of obesity. Thus, a mechanistic link could be proposed between maternal obesity, ER stress and IR in fetal tissues as part of the physiopathology route that connects abnormal intrauterine nutrition with elevated risk of MetS in childhood.
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Keywords
Maternal obesity, Insulin resistance, Er stress, Metabolic syndrome
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