Prenatal ethanol exposure enhances the susceptibility to metabolic syndrome in offspring rats by HPA axis-associated neuroendocrine metabolic programming.
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.
Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071, China; Renmin Hospital of Wuhan University, Wuhan 430060, China.
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Xia
Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071, China.
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Shen
Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071, China.
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Kou
Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071, China.
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Zhang
Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071, China.
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Zhang
Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071, China.
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Wu
Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071, China.
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Li
Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071, China.
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Xiong
Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071, China; Renmin Hospital of Wuhan University, Wuhan 430060, China.
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Yu
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.
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Wang
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000367:Age Factors; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D003345:Corticosterone / Q000097:blood; D059305:Diet, High-Fat; D004198:Disease Susceptibility; D000431:Ethanol / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000097:blood / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007328:Insulin / Q000097:blood; D008055:Lipids / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D018811:Maternal Exposure; D024821:Metabolic Syndrome / Q000097:blood / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017208:Rats, Wistar; D012307:Risk Factors; D015430:Weight Gain / Q000187:drug effects
D015415:Biomarkers; D001786:Blood Glucose; D007328:Insulin; D008055:Lipids; D000431:Ethanol; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone
High-fat diet; Hypothalamic–pituitary–adrenal axis; Intrauterine growth retardation; Metabolic syndrome; Prenatal ethanol exposure