Effects and Interactions of Prenatal Ethanol Exposure, a Post-Weaning High-Fat Diet and Gender on Adult Hypercholesterolemia Occurrence in Offspring Rats

Abstract

Background/Aims: Prenatal ethanol exposure (PEE) could induce intrauterine programming of hypothalamic-pituitary-adrenal axis-associated neuroendocrine metabolism, resulting in intrauterine growth retardation and susceptibility to adult hypercholesterolemia in offspring. This study aimed to analyse the effects and interactions of PEE, a post-weaning high-fat diet (HFD) and gender on the occurrence of adult hypercholesterolemia in offspring rats. Methods: Wistar female rats were treated with ethanol (4 g/kg.d) at gestational days 11-20. The offspring were given a normal diet or HFD after weaning, and the blood cholesterol metabolism phenotype and expression of hepatic cholesterol metabolism related genes were detected in 24-week-old offspring. Furthermore, the interactions among PEE, HFD, and gender on hypercholesterolemia occurrence were analysed. Results: PEE increased the serum total cholesterol (TCH) and low-density lipoprotein-cholesterol (LDL-C) levels and decreased the serum high-density lipoprotein-cholesterol (HDL-C) level in adult offspring rats; the changes in female offspring were greater than those in males. At the same time, the mRNA expression levels of hepatic cholesterol metabolic enzymes (apolipoprotein B (ApoB) and 7α-hydroxylase (CYP7A1))—were increased, while the mRNA expression levels of the scavenger receptor B1 (SR-B1) and LDL receptor (LDLR) were decreased. Furthermore, a three-way ANOVA showed there were interactions among PEE, post-weaning HFD and gender. For PEE offspring, a post-weaning HFD aggravated the elevated hepatic ApoB and CYP7A1 expression and reduced SR-B1 and LDLR expression; the changes in hepatic SR-B1 and CYP7A1 expression were greater in female HFD rats than in males. Conclusion: Our findings suggest that a post-weaning HFD could aggravate offspring hypercholesterolemia caused by PEE and that this mechanism might be associated with hepatic cholesterol metabolic disorders that are aggravated by a post-weaning HFD; hepatic cholesterol metabolism was more sensitive to neuroendocrine metabolic alterations by PEE and a post-weaning HFD in the female offspring than in the male offspring.

Adverse Health Outcomes in Offspring Associated With Fetal Alcohol Exposure: A Systematic Review of Clinical and Preclinical Studies With a Focus on Metabolic and Body Composition Outcomes

“…This study also reported only a subtle, sex‐specific effect on glucose homeostasis (Table ), suggesting that dose rather than timing may be important in development of dyslipidemia in offspring. There also appeared to be a sex‐specific effect, although 2 studies reported stronger phenotypes in males (Gårdebjer et al., ; Pennington et al., ) while one study saw a more pronounced effect in females (Qi et al., ; Table ). Specific examination of the liver revealed PAE‐induced micro‐ and macrovesicular steatosis, increased TG concentration, and dysregulated cholesterol‐metabolizing genes (Table ).…”

Baicalein Neutralizes Hypercholesterolemia-Induced Aggravation of Oxidative Injury in Rats

“…Epidemiological studies showed that the incidence of hypercholesterolemia is mainly associated with poor dietary habits, such as the consumption of foods containing excessive saturated fats and cholesterol, as well as a lack of exercise. The incidence of hypercholesterolemia is higher in women than in men [1]. The World Health Organization reported approximately 2.6 million deaths due to hypercholesterolemia [2].…”

Uteroplacental Insufficiency Impairs Cholesterol Elimination in Adult Female Growth-Restricted Rat Offspring Fed a High-Fat Diet

“…33 High-fat diet feeding after prenatal ethanol exposure exacerbates cholesterol levels in adult female rats more than in male rats, potentially due to greater neuroendocrine metabolic programming in females. 34,35 Consumption of specific nutrients may alter cholesterol metabolism by interaction with sex steroids or greater susceptibility to neuroendocrine metabolic programming in females. 33 Our study has several limitations.…”