Sex-specific increase in susceptibility to metabolic syndrome in adult offspring after prenatal ethanol exposure with post-weaning high-fat diet.

Zheng He,Li Zhang,Hanwen Luo,Jing Li,Hui Wang,Lu Ma,Liaobin Chen

doi:10.1038/srep17679

Abstract

Prenatal ethanol exposure (PEE) is an established risk factor for intrauterine growth retardation. The present study was designed to determine whether PEE can increase the susceptibility of high-fat diet (HFD)-induced metabolic syndrome (MS) in adult offspring in a sex-specific manner, based on a generalized linear model analysis. Pregnant Wistar rats were administered ethanol (4 g/kg.d) from gestational day 11 until term delivery. All offspring were fed either a normal diet or a HFD after weaning and were sacrificed at postnatal week 20, and blood samples were collected. Results showed that PEE reduced serum adrenocorticotropic hormone (ACTH) and corticosterone levels but enhanced serum glucose, insulin, insulin resistant index (IRI), triglyceride and total cholesterol (TC) concentrations. Moreover, the analysis showed interactions among PEE, HFD and sex. In the PEE offspring, HFD aggravated the decrease in ACTH and corticosterone levels and further increased serum glucose, insulin, triglyceride and TC levels. The changes of serum ACTH, glucose and IRI levels in the female HFD rats were greater than those in the male HFD rats. Our findings suggest that PEE enhances the susceptibility to MS induced by HFD in a sex-specific manner, which might be primarily associated with the neuroendocrine metabolic programming by PEE.

Highlights

Environment increases the sensitivity of the peripheral tissues to metabolic hormones, the increased sensitivity improves the fetal survival rate
For the male offspring, the serum adrenocorticotropic hormone (ACTH) and corticosterone concentrations were lower in the male offspring by prenatal ethanol exposure with normal diet (MEN) group (P < 0 .01) than in the male offspring by prenatal vehicle exposure with normal diet (MVN) group, and both concentrations were higher in the male offspring by prenatal ethanol exposure with High-fat diet (HFD) (MEH) group than in the male offspring by prenatal vehicle exposure with HFD (MVH) group (P < 0 .01)
For the female offspring, there were no significant differences between the female offspring by prenatal vehicle exposure with normal diet (FVN) and female offspring by prenatal ethanol exposure with normal diet (FEN) groups in terms of the serum ACTH and corticosterone levels, and the serum ACTH and corticosterone levels were lower in the female offspring by prenatal ethanol exposure with HFD (FEH) group than in the female offspring by prenatal vehicle exposure with HFD (FVH) group (P < 0.01)

Summary

Introduction

Environment increases the sensitivity of the peripheral tissues to metabolic hormones (e.g., glucocorticoid), the increased sensitivity improves the fetal survival rate. Our previous studies confirmed that PEE increases the susceptibility to non-alcoholic fatty liver disease induced by a HFD in rat offspring[23], which may be associated with fetal over-exposure to maternal glucocorticoid, resulting in both functional inhibition of the hypothalamic–pituitary–adrenal (HPA) axis[24] and insulin-like growth factor 1-associated glucose and lipid metabolic alteration in peripheral tissues[23]. Because these changes persist after birth, they manifest as HPA axis dysfunction and glucocorticoid-dependent blood glucose and lipid metabolic alterations in adult rats[25].

Objectives

Methods

Results

Discussion

Conclusion