Abstract
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.
Highlights
Metabolic diseases are increasingly common in the modern society in which high caloric foods are abundant and readily available (Malik et al, 2013)
Often the fatty and sugar components are combined in the chow, we have shown earlier that a free choice high-fat high-sugar diet con sisting of a choice among a solid fatty component (100% beef tallow), a sugary drink (10% sucrose water), a nutritionally complete chow and water, causes prolonged hyperphagia, snacking behaviour and increased food-motivated behaviour in rodents, simulating more closely what is observed in human obesity
We show that food choice and the metabolic response to the free choice high-fat high-sugar diet (fcHFHS) are different for males and females, that Early-life stress (ES) exposure affects food choice upon a mild stressor as well as the metabolic response to the diet in a sex-specific way, and provide evidence that the brain circuits that regulate hedonic food intake are affected by previous ES exposure
Summary
Metabolic diseases are increasingly common in the modern society in which high caloric foods are abundant and readily available (Malik et al, 2013). In 2016, worldwide 39% of adults were overweight and 13% were obese (World Health Organization, 2018). The vulnerability to become overweight or obese is heavily influenced by the perinatal environment, during which a metabolic setpoint is likely established (Bouret, 2009; Bouret and Simerly, 2006; Levin, 2006). It is urgently needed to understand how ES impacts metabolic vulnerability in order to develop strategies to prevent and reduce the incidence of metabolic disorders later in life. Such an early-life-induced setpoint might determine how an organism will respond to its later life nutritional environment, but possibly the food choices an individual makes in the first place
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