Adolescent sugar overconsumption programs food choices via altered dopamine signalling

青少年糖过度消费通过改变多巴胺信号来影响食物选择

• 批准号: BB/Y006496/1
• 负责人: Fabien Naneix
• 金额: $ 70.01万
• 依托单位: University of Aberdeen
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2024
• 资助国家: 英国
• 起止时间: 2024 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FY006496%2F1
• 关键词: Adolescent; sugar; overconsumption; programs; food

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.

根据NHS 2022年的调查，超过60%的英国成年人超重或肥胖，这使得肥胖和糖尿病等相关疾病成为最重要的健康问题之一。在儿童和青少年中，肥胖的发病率增长尤其快，他们在生命早期最终会患上心血管疾病或2型糖尿病。这些非传染性疾病的主要原因之一是过度食用美味的高能量食物。这促使英国政府最近对含糖食品征收“糖税”，并推出“儿童肥胖行动计划”，以减少糖的消耗。尽管有许多关于糖过量摄入对成年人和发育过程中的代谢影响的研究，但对大脑和行为的长期影响，特别是对喂养和食物选择的控制，仍未得到充分研究。青春期似乎是一个关键的脆弱性窗口，因为涉及这些过程的几个大脑区域仍在发育中。在这里，我们将确定青少年过度摄入糖是如何影响大脑功能的，并导致成年后饮食控制的改变。神经调节剂多巴胺是产生这些效果的最佳候选物质。它在控制多种与食物有关的行为中起着核心作用，包括对食物线索（如食物气味/视觉、食物广告）的偏好和反应，这些线索可能会影响食物的选择。我们之前的研究表明，多巴胺系统直到成年后才完全发育，这使得它很容易受到外界的伤害，比如不平衡的饮食习惯。该项目试图回答的主要问题是：1)青春期糖的过量摄入如何影响与进食控制有关的多巴胺信号；2)是否有可能通过操纵多巴胺系统来恢复对进食的适应性控制；3)成年期进食行为的改变是否直接由青春期不发达的多巴胺系统的过度刺激引起。为了回答这些问题，我们将通过观察两种行为来研究老鼠在青春期过度摄入糖的影响：1)与标准的均衡食物相比，它们选择富含脂肪和糖的美味食物的程度；2)食物线索（例如声音总是与食物搭配）如何触发寻找食物和进食。基于我们的初步工作，我们预测糖暴露的小鼠会表现出更高的美味食物摄入量，并且也会表现出更高的由食物线索引发的寻找/进食反应。我们将首先使用一种称为纤维光度法的复杂技术，我们可以使用荧光传感器实时记录行为动物的多巴胺释放，以确定这些控制喂食的变化是否与多巴胺释放的变化有关。我们将把重点放在一个叫做伏隔核的大脑区域，该区域接受高水平的多巴胺，并且已知控制动机行为。接下来，我们将使用一种叫做化学遗传学的技术来控制成年期多巴胺神经元的活动，看看我们是否能逆转青少年过度摄入糖导致的进食控制变化。最后，我们将在青春期小鼠中使用相同的技术来证明，成年小鼠在进食控制方面的缺陷与青春期糖对这些多巴胺神经元的刺激直接相关。通过结合最先进的技术来瞄准、记录和操纵特定的大脑回路，该项目将对青春期含糖食物和饮料对大脑功能的影响提供根本性的见解，为更好地理解现代生活方式对饮食行为和健康的影响铺平道路。