Portal de Periódicos da CAPES

Increased Susceptibility to Metabolic Syndrome in Adult Offspring of Angiotensin Type 1 Receptor Autoantibody-Positive Rats

2012; Mary Ann Liebert, Inc.; Volume: 17; Issue: 5 Linguagem: Inglês

10.1089/ars.2011.4365

1557-7716

Suli Zhang, Xi Zhang, Lihong Yang, Zi Yan, Li Yan, Jue Tian, Xiaoyu Li, Li Song, Li Wang, Xiaoli Yang, Ronghua Zheng, Wayne Bond Lau, Xinliang Ma, Huirong Liu,

Pregnancy and preeclampsia studies

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.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.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.AT1-Ab-positivity of mothers during pregnancy is a previously unrecognized "silent" risk factor for MetS development in their offspring.