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

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 Fetal and Maternal Hepcidin Respond Inversely to Prenatal Alcohol Exposure in a C57BL/6J Mouse Model (P09-010-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Kaylee Helfrich ◽  
Nipun Saini ◽  
Sze Ting (Cecilia) Kwan ◽  
Susan Smith
Keyword(s):  
Rat Model ◽  
Fetal Liver ◽  
Prenatal Alcohol Exposure ◽  
Iron Status ◽  
Alcohol Exposure ◽  
Higher Alcohol ◽  
Regulatory Pathways ◽  
Hepcidin Expression ◽  
Funding Sources ◽  
Prenatal Alcohol

Abstract Objectives Prenatal alcohol exposure (PAE) dysregulates iron metabolism and causes fetal iron deficiency in rats, even when mothers consume sufficient iron. This dysregulation is partly due to PAE-mediated induction of hepcidin, which routes iron to hepatic storage, where it is unavailable for fetal use. It is unclear how PAE upregulates hepcidin; our rat model suggests dysregulation may be via the IL6/STAT3 pathway. The objective of this study is to quantify hepcidin in a mouse PAE model and ascertain via which pathway(s) PAE disrupts hepcidin. Methods C57BL/6J female mice consumed AIN93G diet prior to and throughout pregnancy. Pregnant females received 3g/Kg alcohol or isocaloric maltodextrin (MD) by gavage from gestational day (GD) 8.5-17.5. We analyzed mothers and fetuses at GD17.5. Results Although PAE fetuses had an increased incidence of malformations, fetal weight at GD17.5 did not differ from MD controls (p = 0.800). As in our rat model, PAE upregulated fetal hepatic hepcidin expression (191% increase, p = 0.010). Supporting other studies of chronic alcohol consumption in mice, PAE reduced maternal hepcidin expression, although not significantly (45% decrease, p = 0.055). At a higher alcohol dose (4.5g/Kg, GD13.5-17.5), maternal hepcidin expression was significantly lower than MD controls (59% decrease, p = 0.044). Potential sources of this hepcidin dysregulation include PAE-induced reductions in fetal (24% decrease, p = 0.035) and maternal (61% decrease, p = 0.0004) hepatic Bmp6 expression and elevated fetal hepatic erythropoietin expression (61% increase, p = 0.033). Although decreased BMP6 may contribute to the reduced maternal hepcidin, decreased BMP6 is inconsistent with the elevated fetal hepcidin, and, along with the elevated Epo, may reflect an attempt to increase iron availability in response to PAE. We quantified pro-inflammatory cytokines and found unaltered (Il-6, Ifn-gamma) or decreased (Tnf-alpha) expression in maternal and fetal liver, suggesting a lack of generalized hepatic inflammation in this model. Conclusions PAE exerts different effects on maternal and fetal hepcidin, which may reflect differences in iron status, time of development, or ethanol processing. PAE also dysregulates hepcidin regulatory pathways. Funding Sources T32-DK, R01-AA.

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 Dietary Iron Fortification Normalizes Fetal Hematology, Hepcidin, and Iron Distribution in a Rat Model of Prenatal Alcohol Exposure

2018 ◽  
Vol 42 (6) ◽  
pp. 1022-1033 ◽  
Author(s):  
Shane M. Huebner ◽  
Kaylee K. Helfrich ◽  
Nipun Saini ◽  
Sharon E. Blohowiak ◽  
Adrienne A. Cheng ◽  
...  
Keyword(s):  
Rat Model ◽  
Prenatal Alcohol Exposure ◽  
Alcohol Exposure ◽  
Dietary Iron ◽  
Iron Fortification ◽  
Iron Distribution ◽  
Prenatal Alcohol

Complex Trauma and Prenatal Alcohol Exposure: Clinical Implications

2012 ◽  
Vol 13 (2) ◽  
pp. 32-42 ◽  
Author(s):  
Yvette D. Hyter
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Child Development ◽  
Academic Outcomes ◽  
Complex Trauma ◽  
Prenatal Alcohol Exposure ◽  
Alcohol Exposure ◽  
Clinical Implications ◽  
Prenatal Alcohol ◽  
The Brain

Abstract Complex trauma resulting from chronic maltreatment and prenatal alcohol exposure can significantly affect child development and academic outcomes. Children with histories of maltreatment and those with prenatal alcohol exposure exhibit remarkably similar central nervous system impairments. In this article, I will review the effects of each on the brain and discuss clinical implications for these populations of children.

Prenatal alcohol exposure and signs of minor neurological dysfunction at preschool age

2000 ◽  
Vol 42 (8) ◽  
pp. 508-514 ◽  
Author(s):  
Béatrice Larroque ◽  
Monique Kaminski ◽  
Phillipe Dehaene ◽  
Damien Subtil ◽  
Denis Querleu
Keyword(s):  
Prenatal Alcohol Exposure ◽  
Alcohol Exposure ◽  
Preschool Age ◽  
Neurological Dysfunction ◽  
Minor Neurological Dysfunction ◽  
Prenatal Alcohol

Impact of Moderate Prenatal Alcohol Exposure on Problem Behaviors in Preschool and School Children

2014 ◽  
Vol 46 (2) ◽  
pp. 89-100 ◽  
Author(s):  
Manuela Pfinder ◽  
Stefan Liebig ◽  
Reinhold Feldmann
Keyword(s):  
Problem Behaviors ◽  
Tobacco Smoke ◽  
Prenatal Alcohol Exposure ◽  
Alcohol Exposure ◽  
Smoke Exposure ◽  
Low Ses ◽  
German Health ◽  
Kiggs Study ◽  
Strengths And Difficulties ◽  
Prenatal Alcohol

Data on the relation between moderate prenatal alcohol exposure (PAE) and behavioral disorders are inconsistent, and this raises new questions. We examined (1) the association between moderate PAE and problem behaviors and (2) whether these associations differed by levels of socioeconomic status (SES), fetal smoke exposure, or exposure to environmental tobacco smoke (ETS). Data were taken from the German Health Interview and Examination Survey for Children and Adolescents (KiGGS) study. Parents evaluated children’s behaviors using the Strengths and Difficulties Questionnaire (SDQ). Results showed a slight, but insignificant, increase of problem behaviors in children with moderate PAE. In 3- to 6-year-olds, PAE had a stronger effect on hyperactivity/inattention in combination with fetal smoke exposure (odds ratio = 2.82), than did PAE alone. Effects were not stronger in low-SES children, but they were stronger in children with ETS. We conclude that moderate PAE might have adverse effects on neurodevelopment, with stronger effects in disadvantaged populations. To confirm our preliminary findings, further research should be conducted.

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