The Effects of Early Life Stress, Postnatal Diet Modulation, and Long-Term Western-Style Diet on Later-Life Metabolic and Cognitive Outcomes.

Maralinde R Abbink,Romy Meier,Eline M Van Der Beek,Lidewij Schipper,Paul J Lucassen,Eva F.G Naninck,Aniko Korosi,Cato M.H De Vos

doi:10.3390/nu12020570

Abstract

Early life stress (ES) increases the risk to develop metabolic and brain disorders in adulthood. Breastfeeding (exclusivity and duration) is associated with improved metabolic and neurocognitive health outcomes, and the physical properties of the dietary lipids may contribute to this. Here, we tested whether early life exposure to dietary lipids mimicking some physical characteristics of breastmilk (i.e., large, phospholipid-coated lipid droplets; Concept Nuturis® infant milk formula (N-IMF)), could protect against ES-induced metabolic and brain abnormalities under standard circumstances, and in response to prolonged Western-style diet (WSD) in adulthood. ES was induced by exposing mice to limited nesting material from postnatal day (P) 2 to P9. From P16 to P42, male offspring were fed a standard IMF (S-IMF) or N-IMF, followed by either standard rodent diet (SD) or WSD until P230. We then assessed body composition development, fat mass, metabolic hormones, hippocampus-dependent cognitive function, and neurogenesis (proliferation and survival). Prolonged WSD resulted in an obesogenic phenotype at P230, which was not modulated by previous ES or N-IMF exposure. Nevertheless, ES and N-IMF modulated the effect of WSD on neurogenesis at P230, without affecting cognitive function, highlighting programming effects of the early life environment on the hippocampal response to later life challenges at a structural level.

Highlights

The early perinatal period forms a sensitive time window for metabolic programming and brain development
The western style diet (WSD)-induced obesogenic phenotype was supported by elevated plasma leptin and insulin levels (Fiure 3D; leptin: Fcondition (1, 15.577) = 1.528, p = 0.235, Fpostnatal-diet (1, 20.183) = 0.935, p = 0.345, Fadult-diet (1, 25.145) = 5.956, p = 0.022, no interaction effects; insulin: Fcondition (1, 18.197) = 0.155, p = 0.699, Fpostnatal-diet (1, 23.748) = 0.255, p = 0.618, Fadult-diet (1, 26.744) = 10.957, p = 0.003, no interaction effects)
We show for the first time that early life exposure to a diet containing Nuturis®, better mimicking some of the physical characteristics of lipid globules in mammalian milk, can modulate the hippocampal response to adult WSD at a structural level

Summary

Introduction

The early perinatal period forms a sensitive time window for metabolic programming and brain development. Stress exposure during this time (early life stress; ES) has a long-lasting impact on health outcomes, increasing the vulnerability to both metabolic and mental disorders in adulthood [1,2]. ES in rodents enhances predisposition for diet-induced obesity in adulthood [16,17,18,19], and while ES leads to a leaner phenotype under standard diet (SD) conditions, ES mice accumulate more fat when exposed to WSD later in life, suggesting increased metabolic vulnerability [19]

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