scholarly journals Prenatal alcohol exposure programs offspring disease: Insulin resistance in adult males in a rat model of acute exposure

2019 ◽  
Author(s):  
Tam M T Nguyen ◽  
Sarah E Steane ◽  
Karen M Moritz ◽  
Lisa K Akison
Keyword(s):  
Insulin Resistance ◽  
Blood Glucose ◽  
Chronic Disease ◽  
Alcohol Consumption ◽  
Fetal Development ◽  
Prenatal Alcohol Exposure ◽  
Alcohol Exposure ◽  
Metabolic Dysfunction ◽  
Specific Manner ◽  
Prenatal Alcohol

AbstractAlcohol consumption is highly prevalent amongst women of reproductive age. Given that approximately 50% of pregnancies are unplanned, alcohol has the potential to affect fetal development and program chronic disease in offspring. We examined the effect of an acute but moderate prenatal alcohol exposure (PAE) on glucose metabolism, lipid levels and dietary preference in adolescent and/or adult rat offspring. Pregnant Sprague-Dawley rats received an oral gavage of ethanol (1g/kg maternal body weight, n=9 dams) or an equivalent volume of saline (control, n=8 dams) at embryonic days 13.5 and 14.5. PAE resulted in a blood alcohol concentration of 0.05-0.06% 1h post-gavage in dams. Fasting blood glucose concentration was not affected by PAE in offspring at any age, nor were blood glucose levels during a glucose tolerance test (GTT) in 6-month old offspring (P>0.5). However, there was evidence of insulin resistance in PAE male offspring at 6 months of age, with significantly elevated fasting plasma insulin (P= 0.001), a tendency for increased first phase insulin secretion during the GTT and impaired glucose clearance following an insulin challenge (P= 0.007). This was accompanied by modest alterations in protein kinase B (AKT) signalling in adipose tissue. PAE also resulted in reduced calorie consumption by offspring compared to controls (P= 0.04). These data suggest that a relatively low-level, acute PAE programs metabolic dysfunction in offspring in a sex-specific manner. These results highlight that alcohol consumption during pregnancy has the potential to affect the long-term health of offspring.Key points summaryPrenatal alcohol exposure has the potential to affect fetal development and program chronic disease in offspring.Previous preclinical models typically use high, chronic doses of alcohol throughout pregnancy to examine effects on offspring, particularly on the brain and behaviour.In this study we use a rat model of moderate, acute, prenatal alcohol exposure to determine if this can be detrimental to maintenance of glucose homeostasis in adolescent and adult offspring.Although female offspring were relatively unaffected, there was evidence of insulin resistance in 6-month old male offspring exposed to prenatal alcohol, suggestive of a pre-diabetic state.This result suggests that even a relatively low-dose, acute exposure to alcohol during pregnancy can still program metabolic dysfunction in a sex-specific manner.

scholarly journals Toxic and Teratogenic Effects of Prenatal Alcohol Exposure on Fetal Development, Adolescence, and Adulthood

2021 ◽  
Vol 22 (16) ◽  
pp. 8785
Author(s):  
Dae D. Chung ◽  
Marisa R. Pinson ◽  
Lokeshwar S. Bhenderu ◽  
Michael S. Lai ◽  
Rhea A. Patel ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Fetal Development ◽  
Prenatal Alcohol Exposure ◽  
Alcohol Exposure ◽  
Epigenetic Modifications ◽  
Teratogenic Effects ◽  
Risk Of Disease ◽  
Long Term Consequences ◽  
Prenatal Alcohol

Prenatal alcohol exposure (PAE) can have immediate and long-lasting toxic and teratogenic effects on an individual’s development and health. As a toxicant, alcohol can lead to a variety of physical and neurological anomalies in the fetus that can lead to behavioral and other impairments which may last a lifetime. Recent studies have focused on identifying mechanisms that mediate the immediate teratogenic effects of alcohol on fetal development and mechanisms that facilitate the persistent toxic effects of alcohol on health and predisposition to disease later in life. This review focuses on the contribution of epigenetic modifications and intercellular transporters like extracellular vesicles to the toxicity of PAE and to immediate and long-term consequences on an individual’s health and risk of disease.

scholarly journals Prenatal alcohol exposure programmes offspring disease: insulin resistance in adult males in a rat model of acute exposure

2019 ◽  
Vol 597 (23) ◽  
pp. 5619-5637 ◽  
Author(s):  
Tam M. T. Nguyen ◽  
Sarah E. Steane ◽  
Karen M. Moritz ◽  
Lisa K. Akison
Keyword(s):  
Insulin Resistance ◽  
Rat Model ◽  
Prenatal Alcohol Exposure ◽  
Alcohol Exposure ◽  
Acute Exposure ◽  
Adult Males ◽  
Prenatal Alcohol

Hepatic insulin resistance induced by prenatal alcohol exposure is associated with reduced PTEN and TRB3 acetylation in adult rat offspring

2008 ◽  
Vol 294 (6) ◽  
pp. R1797-R1806 ◽  
Author(s):  
Xing-Hai Yao ◽  
B. L. Grégoire Nyomba
Keyword(s):  
Insulin Resistance ◽  
Insulin Signaling ◽  
Prenatal Alcohol Exposure ◽  
Alcohol Exposure ◽  
Hepatic Insulin Resistance ◽  
Prenatally Exposed ◽  
Adult Rats ◽  
Histone Deacetylase 1 ◽  
Prenatal Alcohol ◽  
And Control

Prenatal alcohol exposure (EtOH) results in insulin resistance in rats of both sexes with increased expression of hepatic gluconeogenic genes and glucose production. To investigate whether hepatic insulin signaling is defective, we studied 3-mo-old female offspring of dams that were given EtOH during pregnancy compared with those from pair-fed and control dams. We performed an intraperitoneal pyruvate tolerance test, determined the phosphorylation status of hepatic phosphoinositide-dependent protein kinase-1 (PDK1), Akt, and PKCζ before and after intravenous insulin bolus, and measured mRNA and in vivo acetylation of TRB3 (tribbles 3) and PTEN (phosphatase and tensin homolog deleted on chromosome ten) as well as the expression of the histone acetylase (HAT) PCAF (p300/CREB-binding protein-associated factor), histone deacetylase-1 (HDAC1), and HAT and HDAC activities. In EtOH compared with pair-fed and control offspring, basal and pyruvate-induced blood glucose was increased, insulin-induced PDK1, Akt, and PKCζ phosphorylation was reduced, and expression of PTEN and TRB3 was increased while their acetylation status was decreased in association with increased HDAC and decreased HAT activities. Thus female adult rats prenatally exposed to EtOH have increased gluconeogenesis, reduced insulin signaling, and increased PTEN and TRB3 expression in the liver. In addition, PTEN and TRB3 are hypoacetylated, which can contribute to Akt-inhibiting activity. These results suggest that hepatic insulin resistance in rats prenatally exposed to EtOH is explained, at least in part, by increased PTEN and TRB3 activity due to both increased gene expression and reduced acetylation.

scholarly journals Prenatal alcohol exposure and facial morphology in a UK cohort

2018 ◽  
Author(s):  
Laurence J Howe ◽  
Gemma C Sharp ◽  
Gibran Hemani ◽  
Luisa Zuccolo ◽  
Stephen Richmond ◽  
...  
Keyword(s):  
Alcohol Consumption ◽  
Prenatal Alcohol Exposure ◽  
Alcohol Exposure ◽  
Self Report ◽  
Facial Morphology ◽  
Normal Range ◽  
Maternal Alcohol ◽  
Maternal Alcohol Consumption ◽  
Maternal Genotype ◽  
Prenatal Alcohol

AbstractHigh levels of prenatal alcohol exposure are known to cause an array of adverse outcomes including foetal alcohol syndrome (FAS); however, the effects of low to moderate exposure are less-well characterised. Previous findings suggest that differences in normal-range facial morphology may be a marker for alcohol exposure and related adverse effects. Therefore, in the Avon Longitudinal Study of Parents and Children, we tested for an association between maternal alcohol consumption and six FAS-related facial phenotypes in their offspring, using both self-report questionnaires and the maternal genotype at rs1229984 in ADH1B as measures of maternal alcohol consumption. In both self-reported alcohol consumption (N=4,233) and rs1229984 genotype (N=3,139) analyses, we found no strong statistical evidence for an association between maternal alcohol consumption and facial phenotypes tested. The directions of effect estimates were compatible with the known effects of heavy alcohol exposure, but confidence intervals were largely centred around zero. We conclude that, in a sample representative of the general population, there is no strong evidence for an effect of prenatal alcohol exposure on normal-range variation in facial morphology.

scholarly journals Retrospective assessment of prenatal alcohol exposure by detection of phosphatidylethanol in stored dried blood spot cards: An objective method for determining prevalence rates of alcohol consumption during pregnancy

2015 ◽  
Vol 4 (2) ◽  
pp. 131-137 ◽  
Author(s):  
Aileen E. Baldwin ◽  
Joseph Jones ◽  
Mary Jones ◽  
Charles Plate ◽  
Douglas Lewis
Keyword(s):  
Alcohol Consumption ◽  
Prenatal Alcohol Exposure ◽  
Alcohol Exposure ◽  
Dried Blood Spot ◽  
Objective Method ◽  
Prevalence Rates ◽  
Retrospective Assessment ◽  
Prenatal Alcohol ◽  
Metabolic Screening ◽  
Blood Spot

Baldwin, A., Jones, J., Jones, M., Plate, C., & Lewis, D. (2015). Retrospective assessment of prenatal alcohol exposure by detection of phosphatidylethanol in stored dried blood spot cards: An objective method for determining prevalence rates of alcohol consumption during pregnancy. The International Journal Of Alcohol And Drug Research, 4(2), 131-137. doi:http://dx.doi.org/10.7895/ijadr.v4i2.209Aims: To analyze the efficacy of screening banked newborn dried blood spots (DBS) for detection of phosphatidylethanol(PEth), a direct alcohol biomarker, with the purpose of performing a retrospective assessment of statewide prevalence rates ofalcohol consumption in late pregnancy that results in risky prenatal alcohol exposure.Design: Residual DBS samples collected for newborn screening and stored by a state department of public health wereexamined for concentrations of PEth. The prevalence of prenatal alcohol exposure, as determined by this direct alcoholbiomarker, was compared to prevalence rates of alcohol consumption during pregnancy that have been derived from multiplestate-based and national studies using maternal self-report surveys.Setting: DBS cards representative of the general newborn population were collected from multiple hospitals across a singlemidwestern state.Participants: Two hundred fifty anonymous newborn DBS collected for routine metabolic screening in a midwestern state wererequested through the Virtual Repository of Dried Blood Spots.Measures: Concentrations of PEth, a highly specific biomarker of alcohol consumption, were analyzed using a liquidchromatography–tandem mass spectrometry method validated by our laboratory.Findings: Of 2 50 D BS e xamined, 4 % w ere p ositive f or PEth ( PEth ≥ 8 n g/ml) which is indicative of exposure to maternalalcohol consumption during the last month of pregnancy.Conclusions: Detection of PEth from newborn DBS cards can identify prenatal alcohol exposure and also be used forretrospective surveillance of alcohol consumption during the last three to four weeks of pregnancy, using specimens that arecollected for routine metabolic screening and stored by many state health departments.

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