Adolescent sugar overconsumption programs food choices via altered dopamine signalling
Lead Research Organisation:
University of Aberdeen
Department Name: Sch of Medicine, Medical Sci & Nutrition
Abstract
According to the NHS 2022 survey, more than 60% of the UK adult population is overweight or obese, making obesity and associated diseases like diabetes one of the most important health issues. Obesity incidence is especially growing fast in children and teens who end up developing cardiovascular diseases or type 2 diabetes early in life. One of the main causes of these non-communicable diseases is the overconsumption of highly palatable energy-rich foods. This recently prompted the UK government to introduce a 'sugar tax' on sweetened foods and to launch the 'Childhood obesity action plan' to reduce sugar consumption. Despite numerous studies on metabolic effects of sugar overconsumption in adults and during development, the long-term impact on brain and behaviour, especially on the control of feeding and food choice, remains understudied. Adolescence appears to be a crucial vulnerability window as several brain regions involved in these processes are still under development. Here we will determine how adolescent sugar overconsumption impacts brain functioning and leads to altered control of feeding at adulthood.
The neuromodulator dopamine is the perfect candidate for these effects. It plays a central role in controlling multiple food-related behaviours including preference and response to food cues (e.g. food smell/sight, food advertisements) which may bias food choice. We have previously shown that the dopamine system is not fully developed until adulthood, leaving it vulnerable to external insults such as unbalanced dietary habits. The main questions that this project seeks to answer are i) how does sugar overconsumption during adolescence impact dopamine signalling in relation to the control of feeding, ii) is it possible to restore adaptive control of feeding by manipulating the dopamine system, and iii) are alterations of feeding behaviours at adulthood directly caused by the overstimulation of the underdeveloped dopamine system during adolescence.
To answer these questions, we will investigate in mice the effect of sugar overconsumption during adolescence by looking at two kinds of behaviour: 1) how much they choose a very palatable food enriched in fat and sugar compared to standard balanced food, and 2) how food cues (e.g. sound always paired with food) can trigger food-seeking and eating. Based on our preliminary work, we predict that sugar-exposed mice will exhibit a higher intake of the palatable food and will also express higher seeking/eating responses triggered by food cues. We will first use a sophisticated technique called fibre photometry with which we can record dopamine release in real time in behaving animal using fluorescent sensors to determine if these changes in the control of feeding are associated with changes in dopamine release. We will focus on a brain region called the nucleus accumbens, receiving high levels of dopamine and known to control motivated behaviours. Next, we will manipulate the activity of dopamine neurons at adulthood using a technique called chemogenetics to see if we can reverse the changes in the control of feeding cause by adolescent sugar overconsumption. Finally, we will use the same technique in adolescent mice to demonstrate that adult deficits in the control of feeding is directly linked to the stimulation of these dopamine neurons by sugar during adolescence.
By combining state-of-the-art techniques to target, record and manipulate specific brain circuits, this project will give fundamental insights into the impact of sugary foods and drinks during adolescence on brain functioning, paving the way to a better understanding of the effect of the modern lifestyle on feeding behaviours and health.
The neuromodulator dopamine is the perfect candidate for these effects. It plays a central role in controlling multiple food-related behaviours including preference and response to food cues (e.g. food smell/sight, food advertisements) which may bias food choice. We have previously shown that the dopamine system is not fully developed until adulthood, leaving it vulnerable to external insults such as unbalanced dietary habits. The main questions that this project seeks to answer are i) how does sugar overconsumption during adolescence impact dopamine signalling in relation to the control of feeding, ii) is it possible to restore adaptive control of feeding by manipulating the dopamine system, and iii) are alterations of feeding behaviours at adulthood directly caused by the overstimulation of the underdeveloped dopamine system during adolescence.
To answer these questions, we will investigate in mice the effect of sugar overconsumption during adolescence by looking at two kinds of behaviour: 1) how much they choose a very palatable food enriched in fat and sugar compared to standard balanced food, and 2) how food cues (e.g. sound always paired with food) can trigger food-seeking and eating. Based on our preliminary work, we predict that sugar-exposed mice will exhibit a higher intake of the palatable food and will also express higher seeking/eating responses triggered by food cues. We will first use a sophisticated technique called fibre photometry with which we can record dopamine release in real time in behaving animal using fluorescent sensors to determine if these changes in the control of feeding are associated with changes in dopamine release. We will focus on a brain region called the nucleus accumbens, receiving high levels of dopamine and known to control motivated behaviours. Next, we will manipulate the activity of dopamine neurons at adulthood using a technique called chemogenetics to see if we can reverse the changes in the control of feeding cause by adolescent sugar overconsumption. Finally, we will use the same technique in adolescent mice to demonstrate that adult deficits in the control of feeding is directly linked to the stimulation of these dopamine neurons by sugar during adolescence.
By combining state-of-the-art techniques to target, record and manipulate specific brain circuits, this project will give fundamental insights into the impact of sugary foods and drinks during adolescence on brain functioning, paving the way to a better understanding of the effect of the modern lifestyle on feeding behaviours and health.
Technical Summary
Sugar is the main source of excess daily calories in our diets, especially amongst children and adolescents. As sugar overconsumption is one of the main causes of the increased prevalence of obesity and type 2 diabetes, it is crucial to understand the long-term impact of such dietary habits during early life on feeding behaviours at adulthood. Based on our previous work and our preliminary results, we hypothesise that adolescent sugar overconsumption alters feeding behaviours, including unhealthy food choices and exacerbated response to food cues in adulthood, related to nucleus accumbens dopamine signalling dysfunctions.
Mice will have continuous access to 5% sucrose solution in addition to a balanced diet during all their adolescence. At adulthood we will investigate feeding behaviours using i) a dietary choice protocol with continuous access to standard chow and high-fat/high-sugar obesogenic diet for several weeks, and ii) Pavlovian conditioning procedures to explore cue-driven food-seeking responses (conditioned reinforcement and cue-potentiated feeding).
First, we will record NAc dopamine release in behaving control and adolescent sucrose-exposed animals using fibre photometry and a fluorescent dopamine sensor in response to food and food cues at adulthood (Aim 1). Second, we will determine if the manipulation of specific dopamine circuits at adulthood using chemogenetic (DREADD) approaches is able to reverse alterations in feeding behaviours induced by adolescent sugar overconsumption. Finally, we will explore if these changes in the control of feeding behaviours are directly linked to an overstimulation of the underdeveloped dopamine system using a drinking-driven chemogenetic activation of this system during adolescence in absence of sugar.
Mice will have continuous access to 5% sucrose solution in addition to a balanced diet during all their adolescence. At adulthood we will investigate feeding behaviours using i) a dietary choice protocol with continuous access to standard chow and high-fat/high-sugar obesogenic diet for several weeks, and ii) Pavlovian conditioning procedures to explore cue-driven food-seeking responses (conditioned reinforcement and cue-potentiated feeding).
First, we will record NAc dopamine release in behaving control and adolescent sucrose-exposed animals using fibre photometry and a fluorescent dopamine sensor in response to food and food cues at adulthood (Aim 1). Second, we will determine if the manipulation of specific dopamine circuits at adulthood using chemogenetic (DREADD) approaches is able to reverse alterations in feeding behaviours induced by adolescent sugar overconsumption. Finally, we will explore if these changes in the control of feeding behaviours are directly linked to an overstimulation of the underdeveloped dopamine system using a drinking-driven chemogenetic activation of this system during adolescence in absence of sugar.
