Sex dependent impact of gestational stress on predisposition to eating disorders and metabolic disease

妊娠期应激对饮食失调和代谢疾病易感性的性别差异影响

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作者:Mariana Schroeder ,Mira Jakovcevski ,Tamar Polacheck ,Yonat Drori ,Shifra Ben-Dor ,Simone Röh ,Alon Chen

Abstract

Objective: Vulnerability to eating disorders (EDs) is broadly assumed to be associated with early life stress. However, a careful examination of the literature shows that susceptibility to EDs may depend on the type, severity and timing of the stressor and the sex of the individual. We aimed at exploring the link between chronic prenatal stress and predisposition to EDs and metabolic disease. Methods: We used a chronic variable stress protocol during gestation to explore the metabolic response of male and female offspring to food restriction (FR), activity-based anorexia (ABA), binge eating (BE) and exposure to high fat (HF) diet. Results: Contrary to controls, prenatally stressed (PNS) female offspring showed resistance to ABA and BE and displayed a lower metabolic rate leading to hyperadiposity and obesity on HF diet. Male PNS offspring showed healthy responses to FR and ABA, increased propensity to binge and improved coping with HF compared to controls. We found that long-lasting abnormal responses to metabolic challenge are linked to fetal programming and adult hypothalamic dysregulation in PNS females, resulting from sexually dimorphic adaptations in placental methylation and gene expression. Conclusions: Our results show that maternal stress may have variable and even opposing effects on ED risk, depending on the ED and the sex of the offspring. Keywords: Activity based anorexia; Binge eating; Early life programming; Metabolic syndrome; Obesity; Stress.

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