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.
Level 5 - mechanism / opinion, no new human data
Preclinical animal experiment in rats
PubMed 25733565 · doi:10.1096/fj.14-268979
What was done
Sprague-Dawley female rats received an isocaloric control liquid diet or a liquid diet containing alcohol (12% volume/volume) strictly during the periconceptional period, spanning from 4 days before conception until gestational day 4. At late gestation, fetal livers were evaluated for DNA methyltransferase (DNMT1, DNMT3a, DNMT3b) mRNA expression. At 6 months of age, adult offspring were assessed for fasting plasma glucose, glucose tolerance, insulin sensitivity, hepatic gluconeogenesis, and peripheral protein kinase B (AKT) signaling. A subset of offspring was placed on a postnatal high-fat and cholesterol diet starting at 3 months of age to determine interactive metabolic effects.
What was found
At 6 months of age, offspring exposed to periconceptional alcohol exhibited elevated fasting plasma glucose (~10% to 25% increase, P < 0.05), impaired glucose tolerance (P < 0.05), and decreased insulin sensitivity (P < 0.01). These changes co-occurred with increased hepatic gluconeogenesis and sex-specific alterations in AKT signaling. Late-gestation fetal livers displayed a 1.5- to 1.9-fold increase in DNMT1, DNMT3a, and DNMT3b mRNA expression (P < 0.05). Postnatal high-fat feeding led to a ~2-fold increase in insulin levels (P < 0.001) and exacerbated metabolic dysfunction in alcohol-exposed males, but produced no additive metabolic deterioration in exposed females.
Why it matters
This study shows that maternal alcohol intake restricted strictly to the brief window around conception can program persistent glucose intolerance and insulin resistance in adult offspring, identifying a potential pre-implantation developmental vulnerability.
Limits
The investigation was conducted solely in a rat model, which limits direct translational application to human pregnancy and metabolism. The abstract does not disclose the total number of dams or offspring evaluated. Epigenetic assessment in the abstract was limited to DNMT transcript levels rather than direct genome-wide or gene-specific DNA methylation mapping.
Cited by
- supports In an animal model, consuming the equivalent of five standard drinks around the time of conception caused offspring at 6 months of age to have impaired glucose tolerance and reduced insulin sensitivity.