Early-life stress (ES) is associated with increased risk to develop metabolic disorders such as obesity, possibly in a sex-specific way. We have shown that ES in mice leads to an acute and lasting reduction in adipose tissue and leptin levels, thus to a seemingly leaner phenotype in both sexes. In addition, we showed that ES-exposed mice, although starting from a leaner phenotype, accumulate more fat in response to a moderate obesogenic diet, and that ES leads to alterations in the hypothalamic circuitry early in life. This data leads us to hypothesize that these metabolic alterations might contribute to persistent alterations in morphology and function of the hypothalamic feeding circuitry, possibly affecting food preference, and that these changes in concert might lead to the increased vulnerability of ES-exposed individuals to develop obesity later in life.

We used an established ES mouse model, in which we provide limited nesting and bedding material from postnatal day 2-9, and characterized hypothalamic neuropeptides in adult male mice as well as food preference with a free choice high-fat high-sugar diet (fcHFHS) in both sexes. Overall, ES did not seem to affect hypothalamic neuropeptide levels on the long-term, nor food preference when exposed to a fcHFHS diet. However, we observed strong sex effects on food preference. Interestingly, when exposed to a short (metabolic) stressor, ES-exposed females, but not males, consumed more fat than controls. Moreover, fcHFHS diet and ES exposure seemed to modulate abdominal fat and glucose levels, in a sex-specific manner. We conclude that ES does not seem to change the hypothalamic circuitry or food preference on the long-term, under basal circumstances. Under stressful conditions however, ES-exposed animals may respond differently, in a sex-specific manner. We are currently investigating possible underlying mechanisms for these sex effects, and aim to unravel why ES-exposed animals show a different response to the diet.