Adult food choices depend on sex and exposure to early-life stress: Underlying brain circuitry, adipose tissue adaptations and metabolic responses

Exposure to early-life stress (ES) increases the risk to develop obesity later in life, and these effects may be sex-specific, but it is currently unknown what underlies the ES-induced metabolic vulnerability. We have previously shown that ES leads to a leaner phenotype under standard chow diet conditions, but to increased fat accumulation when exposed to an unhealthy obesogenic diet. However these diets were fed without a choice. An important, yet under investigated, element contributing to the development of obesity in humans is the choice of the food. There is initial evidence that ES leads to altered food choices but a thorough testing on how ES affects the choice of both the fat and sugar component, and if this is similar in males and females, is currently missing. We hypothesized that ES increases the choice for unhealthy foods, while it at the same time also affects the response to such a diet. In a mouse model for ES, in which mice are exposed to limited nesting and bedding material from postnatal day (P)2-P9, we investigated if ES exposure affected i) food choice with a free choice high-fat high-sugar diet (fcHFHS), ii) the response to such a diet, iii) the brain circuits that regulate food intake and food reward and iv) if such ES effects are sex-specific. We show that there are sex differences in food choice under basal circumstances, and that ES increases fat intake in females when exposed to a mild acute stressor. Moreover, ES impacts the physiologic response to the fcHFHS and the brain circuits regulating food intake in sex-specific manner. Our data highlight sex-specific effects of ES on metabolic functioning and food choice.