Increased susceptibility to metabolic syndrome in adult offspring of angiotensin type 1 receptor autoantibody-positive rats.
Publication/Presentation Date
9-1-2012
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.
Volume
17
Issue
5
First Page
733
Last Page
743
ISSN
1557-7716
Published In/Presented At
Zhang, S., Zhang, X., Yang, L., Yan, Z., Yan, L., Tian, J., Li, X., Song, L., Wang, L., Yang, X., Zheng, R., Lau, W. B., Ma, X., & Liu, H. (2012). Increased susceptibility to metabolic syndrome in adult offspring of angiotensin type 1 receptor autoantibody-positive rats. Antioxidants & redox signaling, 17(5), 733–743. https://doi.org/10.1089/ars.2011.4365
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
22304458
Department(s)
Administration and Leadership
Document Type
Article