Prenatal ethanol exposure enhances the susceptibility to metabolic syndrome in offspring rats by HPA axis-associated neuroendocrine metabolic programming

• Ethanol induced a high risk to metabolic diseases in male offspring rats.
• Ethanol induced HPA axis dysfunction in IUGR male offspring rats fed by high-fat diet.
• Ethanol induced neuroendocrine metabolic programming alteration in male offspring rats.
• Ethanol induced metabolic injury of multiple organs in male offspring rats.

ObjectiveThe present study was designed to demonstrate that prenatal ethanol exposure (PEE) could enhance the susceptibility of high-fat diet-induced metabolic syndrome (MS) in adult male offspring via a hypothalamic–pituitary–adrenal (HPA) axis-associated neuroendocrine metabolic programmed mechanism.MethodsPregnant Wistar rats were intragastricly administrated ethanol 4 g/kg·d from gestational day 11 until term delivery. All male offspring were fed with high-fat diet after weaning, exposed to an unpredictable chronic stress at postnatal week (PW) 17 and sacrificed at PW20.ResultsIn PEE group, body weight presented a “catch-up growth” pattern, and the HPA axis exhibited a lower basal activity but an enhanced sensitivity to chronic stress, leading to increased levels of serum glucose, insulin, insulin resistant index, total cholesterol and low-density lipoprotein-cholesterol, and decreased levels of high-density lipoprotein-cholesterol. Furthermore, many lipid droplets and vacuolar degeneration were observed in the hypothalamus, pituitary gland and liver.ConclusionsPEE induces enhanced susceptibility to MS in adult offspring fed with high-fat diet, and the underlying mechanism involves a HPA axis-associated neuroendocrine metabolic programming alteration.