L P Xia1, L Shen2, H Kou2, B J Zhang2, L Zhang2, Y Wu2, X J Li2, J Xiong2, Y Yu1, H Wang3. 1. Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071, China; Renmin Hospital of Wuhan University, Wuhan 430060, China. 2. Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071, China. 3. Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071, China; Hubei Provincial Key Laboratory of Developmentally Originated Disorder, Wuhan 430071, China. Electronic address: wanghui19@whu.edu.cn.
Abstract
OBJECTIVE: The 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. METHODS: Pregnant 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. RESULTS: In 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. CONCLUSIONS: PEE 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.
OBJECTIVE: The 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. METHODS: Pregnant 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. RESULTS: In 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. CONCLUSIONS: PEE 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.
Authors: Emilie R Lunde; Shannon E Washburn; Michael C Golding; Shameena Bake; Rajesh C Miranda; Jayanth Ramadoss Journal: Alcohol Clin Exp Res Date: 2016-06-02 Impact factor: 3.455