Increased susceptibility to metabolic syndrome in adult offspring of angiotensin type 1 receptor autoantibody-positive rats.
OBJECTIVE
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.


METHODS
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.


CONCLUSIONS
AT1-Ab-positivity of mothers during pregnancy is a previously unrecognized "silent" risk factor for MetS development in their offspring.
Department of Physiology, Shanxi Medical University, Taiyuan, People's Republic of China.
Suli
S
Zhang
Xi
X
Zhang
Lihong
L
Yang
Zi
Z
Yan
Li
L
Yan
Jue
J
Tian
Xiaoyu
X
Li
Li
L
Song
Li
L
Wang
Xiaoli
X
Yang
Ronghua
R
Zheng
Wayne Bond
WB
Lau
Xinliang
X
Ma
Huirong
H
Liu
D000818:Animals; D000831:Animals, Newborn; D001323:Autoantibodies / Q000276:immunology*; D005260:Female; D007333:Insulin Resistance; D024821:Metabolic Syndrome / Q000473:pathology*; D011247:Pregnancy; D051381:Rats; D044140:Receptor, Angiotensin, Type 1 / Q000276:immunology*
D001323:Autoantibodies; D044140:Receptor, Angiotensin, Type 1