Abstract
Excessive exposure to alcohol prenatally has a myriad of detrimental effects on the health and well-being of the offspring. It is unknown whether chronic low-moderate exposure of alcohol prenatally has similar and lasting effects on the adult offspring’s health. Using our recently developed Sprague-Dawley rat model of 6% chronic prenatal ethanol exposure, this study aimed to determine if this modest level of exposure adversely affects glucose homeostasis in male and female offspring aged up to eight months. Plasma glucose concentrations were measured in late fetal and postnatal life. The pancreas of 30 day old offspring was analysed for β-cell mass. Glucose handling and insulin action was measured at four months using an intraperitoneal glucose tolerance test and insulin challenge, respectively. Body composition and metabolic gene expression were measured at eight months. Despite normoglycaemia in ethanol consuming dams, ethanol-exposed fetuses were hypoglycaemic at embryonic day 20. Ethanol-exposed offspring were normoglycaemic and normoinsulinaemic under basal fasting conditions and had normal pancreatic β-cell mass at postnatal day 30. However, during a glucose tolerance test, male ethanol-exposed offspring were hyperinsulinaemic with increased first phase insulin secretion. Female ethanol-exposed offspring displayed enhanced glucose clearance during an insulin challenge. Body composition and hepatic, muscle and adipose tissue metabolic gene expression levels at eight months were not altered by prenatal ethanol exposure. Low-moderate chronic prenatal ethanol exposure has subtle, sex specific effects on glucose homeostasis in the young adult rat. As aging is associated with glucose dysregulation, further studies will clarify the long lasting effects of prenatal ethanol exposure.
Highlights
It is well recognised that an adverse intrauterine environment can have long lasting effects on the subsequent health of the adult
One clinical marker for an adverse intrauterine environment is low birth weight, a result of decreased fetal growth, which has been associated with characteristics of the metabolic syndrome including impaired glucose tolerance, insulin resistance and type 2 diabetes in adult life [1,2,3,4,5]
Using a rodent model of chronic low-moderate dose maternal EtOH consumption, we have shown that this type of fetal EtOH exposure induces fetal hypoglycaemia that is independent of maternal glucose status
Summary
It is well recognised that an adverse intrauterine environment can have long lasting effects on the subsequent health of the adult. The thrifty phenotype hypothesis suggests that poor fetal nutrition alters fetal metabolism to promote immediate survival [16] This is achieved by increasing metabolic efficiency and storage of fuel sources in order to protect important tissues such as the brain, at the expense of others such as skeletal muscle and the endocrine pancreas [17]. These fetal adaptations are thought to remain in postnatal life where the altered metabolism of the offspring is incompatible with the increased nutrient supply, thereby placing the offspring at increased risk of obesity and adult onset type 2 diabetes
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