Abstract
Early-life stress (ES) exposure increases the risk of developing obesity. Breastfeeding can markedly decrease this risk, and it is thought that the physical properties of the lipid droplets in human milk contribute to this benefit. A concept infant milk formula (IMF) has been developed that mimics these physical properties of human milk (Nuturis®, N-IMF). Previously, we have shown that N-IMF reduces, while ES increases, western-style diet (WSD)-induced fat accumulation in mice. Peripheral and central inflammation are considered to be important for obesity development. We therefore set out to test the effects of ES, Nuturis® and WSD on adipose tissue inflammatory gene expression and microglia in the arcuate nucleus of the hypothalamus. ES was induced in mice by limiting the nesting and bedding material from postnatal day (P) 2 to P9. Mice were fed a standard IMF (S-IMF) or N-IMF from P16 to P42, followed by a standard diet (STD) or WSD until P230. ES modulated adipose tissue inflammatory gene expression early in life, while N-IMF had lasting effects into adulthood. Centrally, ES led to a higher microglia density and more amoeboid microglia at P9. In adulthood, WSD increased the number of amoeboid microglia, and while ES exposure increased microglia coverage, Nuturis® reduced the numbers of amoeboid microglia upon the WSD challenge. These results highlight the impact of the early environment on central and peripheral inflammatory profiles, which may be key in the vulnerability to develop metabolic derangements later in life.
Highlights
Exposure to adversity in the perinatal period increases one’s risk of developing metabolic diseases, such as obesity, later in life
Females were housed in pairs for another week in a clean cage, after which pregnant females were single-housed in a cage with filtertop equipped with standard bedding and nesting material (type 2 conventional cage, sawdust, one square piece of cotton nesting material (5 × 5 cm; Technilab-BMI, Someren, The Netherlands))
While prolonged western-style diet (WSD) increased the number of amoeboid microglia, postnatal diet with Nuturis® consistently reduced these numbers when fed WSD, independent of previous Early-life stress (ES) exposure
Summary
Exposure to adversity in the perinatal period increases one’s risk of developing metabolic diseases, such as obesity, later in life. Metabolic diseases are increasingly prevalent in modern society. According to the World Health Organization, 50% of people in the European Union are overweight or obese. The number of people adopting unhealthy “Western-style” diets has risen [1]. These diets are characterized among others by a higher intake of (saturated) fats, and known to contribute to obesity development [2]. Understanding the (neuro)biological substrates that increase the risk of developing metabolic diseases is important
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