Maternal alcohol intake around the time of conception causes glucose intolerance and insulin insensitivity in rat offspring, which is exacerbated by a postnatal high-fat diet.
Alcohol consumption throughout pregnancy can cause metabolic dysregulation, including glucose intolerance in progeny. This study determined if periconceptional (PC) alcohol (12% v/v in a liquid diet) (PC:EtOH) consumed exclusively around conception results in similar outcomes in Sprague-Dawley rats. Control (C) rats were given a liquid diet containing no alcohol but matched to ensure equal caloric intake. PC maternal alcohol intake (from 4 days before conception until day 4 of gestation), resulted in offspring with elevated fasting plasma glucose (∼10-25%, P < 0.05), impaired glucose tolerance (P < 0.05), and decreased insulin sensitivity (P < 0.01) at 6 months of age. This was associated with increased hepatic gluconeogenesis and sex-specific alterations in peripheral protein kinase B (AKT) signaling. These changes were accompanied by increased mRNA expression of DNA methyltransferases (DNMTs) 1, 3a, and 3b (1.5- to 1.9-fold, P < 0.05) in fetal liver in late gestation, suggesting PC:EtOH may cause epigenetic changes that predispose offspring to metabolic dysfunction. Exposure to a postnatal (PN) high-fat and cholesterol diet (HFD) from 3 months of age caused hyperinsulinemia (∼2-fold increase, P < 0.001) and exacerbated the metabolic dysfunction in male offspring exposed to PC:EtOH but had no additive effects in females. Given many women may drink alcohol while planning a pregnancy, it is crucial to increase public awareness regarding the effects of alcohol consumption around conception on offspring health.
*Biomedical Sciences, The University of Queensland, St. Lucia, Queensland, Australia; and The Department of Physiology, The University of Melbourne, Parkville, Victoria, Australia.
Emelie M
EM
Gårdebjer
*Biomedical Sciences, The University of Queensland, St. Lucia, Queensland, Australia; and The Department of Physiology, The University of Melbourne, Parkville, Victoria, Australia.
Stephen T
ST
Anderson
*Biomedical Sciences, The University of Queensland, St. Lucia, Queensland, Australia; and The Department of Physiology, The University of Melbourne, Parkville, Victoria, Australia.
Marie
M
Pantaleon
*Biomedical Sciences, The University of Queensland, St. Lucia, Queensland, Australia; and The Department of Physiology, The University of Melbourne, Parkville, Victoria, Australia.
Mary E
ME
Wlodek
*Biomedical Sciences, The University of Queensland, St. Lucia, Queensland, Australia; and The Department of Physiology, The University of Melbourne, Parkville, Victoria, Australia k.moritz@uq.edu.au.
Karen M
KM
Moritz
D000428:Alcohol Drinking / Q000009:adverse effects*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics; D059305:Diet, High-Fat / Q000009:adverse effects; D005260:Female; D005306:Fertilization; D005333:Fetus / Q000378:metabolism; D005943:Gluconeogenesis; D018149:Glucose Intolerance / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D006655:Histone Deacetylases / Q000235:genetics; D006801:Humans; D007333:Insulin Resistance; D008099:Liver / Q000378:metabolism; D008297:Male; D023421:Models, Animal; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics; D015398:Signal Transduction
D001786:Blood Glucose; D012333:RNA, Messenger; D004248:DNA (Cytosine-5-)-Methyltransferases; D006655:Histone Deacetylases
developmental programming; diabetes; gene expression; gluconeogenesis; metabolic pathways