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This article is peer reviewed. The original version is published in Antioxidants and Redox Signaling, 2012 Sep 1;17(5):733-43. © Mary Ann Liebert, Inc.


Abstract Aims: Abnormal fetal and early postnatal growth is closely associated with adult-onset metabolic syndrome (MetS). However, the underlying etiological factors remain complex. The presence of the autoantibody against the angiotensin II type 1 receptor (AT1-Ab), a known risk factor for pre-eclampsia, may create a suboptimal intrauterine fetal environment. The current study investigated whether middle-aged offspring of AT1-Ab-positive mothers were prone to metabolic disorder development. Results: The AT1-Abs was detected in placental trophoblastic cells, capillary endothelium, and milk of pregnant rats actively immunized with the second extracellular loop of the AT1 receptor. AT1-Abs in newborn rats induced vasoconstriction, increased intracellular-free Ca(2+) in vitro, and was undetectable 7 weeks later. Immunized group offspring exhibited increased weight variability and insulin resistance at 40 weeks of age under a normal diet, evidenced by elevated fasting serum insulin and homeostasis model assessment score compared with the vehicle control. To further observe metabolic alterations, the offspring were given a high-sugar diet (containing 20% sucrose) 40-48 weeks postnatally. The fasting plasma glucose in immunized group offspring was markedly increased. Concomitantly, these offspring manifested increased visceral adipose tissue, increased fatty liver, increased triglycerides, decreased high-density lipoprotein cholesterol, and decreased adiponectin levels, indicative of MetS. Innovation: AT1-Abs could be transferred from mother to offspring via the placenta and milk. Moreover, offspring of an AT1-Ab-positive mother were more vulnerable to MetS development in middle age. Conclusion: AT1-Ab-positivity of mothers during pregnancy is a previously unrecognized "silent" risk factor for MetS development in their offspring. Antioxid. Redox Signal. 17, 733-743.

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