Examining the biological mechanisms that underlie the drive to eat in humans

检查人类进食动力背后的生物机制

• 批准号: MR/X036804/1
• 负责人: Mark Evan Hopkins
• 金额: $ 243.27万
• 依托单位: University of Leeds
• 依托单位国家: 英国
• 项目类别: Fellowship
• 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=MR%2FX036804%2F1
• 关键词: Examining; biological; mechanisms; underlie; drive

RESEARCH CONTEXT: A major weakness in our current understanding of human appetite is the inability to adequately explain the biological mechanisms underpinning the drive to eat. This drive is perceived as hunger and understanding the biological origins of hunger is fundamental to the management of appetite during under-and-over-nutrition, ageing, and diseases where appetite is impaired. Current scientific approaches focus almost exclusively on feedback signals from adipose tissue (fat) and the gastrointestinal tract (stomach and intestine) when attempting to explain the biological control of appetite. However, these approaches account for the suppression of appetite following meal consumption (e.g., feelings of fullness and satiety) rather than the signals that drive eating. I have recently provided novel evidence that the metabolic activity of fat-free mass (FFM) creates a drive to eat in humans to ensures the energy needs of key tissues and organs are met. However, the signals linking FFM to hunger are unknown and I will use this fellowship to identify these. By positioning FFM as key feature of appetite, my research also provides new opportunities to understand how changes in appetite oppose weight loss. Increased hunger and food intake during energy restriction are one of the key reasons why individuals struggle to achieve and maintain weight loss. However, these changes in hunger are inconsistent; some individuals report increased hunger while others show no change or a decrease in hunger. At present, we cannot adequately explain why. There has been little attempt to date to examine how losses of FFM during weight loss, which occur alongside losses of fat, influence weight-induced changes in appetite. By establishing how and why FFM loss promotes increased appetite and food intake following weight loss, I will provide new understanding of why people fail to maintain weight loss and facilitate the design of novel strategies that counter these changes in appetite. AIMS: My fellowship will develop a new biological model of human appetite that incorporates FFM and its associated energetic demands as determinants of hunger. I will apply this model to conditions of weight loss to explain how changes in appetite act to resist weight loss. To achieve this, I will:1. Conduct a weight loss study in adults with obesity that includes detailed laboratory measures of body composition, energy expenditure and appetite alongside free-living measures of appetite, food intake, energy expenditure derived using wearable wrist-worn activity monitors (Fitbits) and weekly body weights (Bluetooth scales).2. Examine FFM as novel determinant of the drive to eat when individuals are weight stable (i.e., in energy balance) and following weight loss using objective measures of food intake under laboratory and free-living environments.3. Identify the signals linking FFM to hunger and food intake.APPLICATIONS & BENEFITS: By targeting the mechanisms that drive rather than suppress hunger, my fellowship will provide novel insight into the factors that influence appetite in health and disease. Examining these mechanisms during weight loss will provide fundamental insight into how changes in appetite oppose weight loss, facilitating the design of targeted interventions that counter these changes. Quantifying changes in free-living food intake and energy expenditure during weight loss will identify optimal timings for nutritional or behavioural support to better inform nutritional and public health guidelines. By identifying the signals linking FFM to food intake, I will provide important new insight with clinical relevance for those interested in conditions characterised by appetite impairment (ageing, cancers, diabetes). This will also provide opportunities for pharmacological industries interested in body weight control by identifying novel targets that block the specific mechanisms underlying the drive to eat.

研究背景：我们目前对人类食欲的理解的一个主要弱点是无法充分解释支撑进食动力的生物学机制。这种驱动力被认为是饥饿，了解饥饿的生物学起源对于在营养不足和营养过剩、衰老和食欲受损的疾病期间管理食欲至关重要。当前的科学方法在试图解释食欲的生物控制时，几乎完全集中在脂肪组织（脂肪）和胃肠道（胃和肠）的反馈信号上。然而，这些方法解释了进餐后食欲的抑制（例如，饱腹感和饱足感），而不是驱动进食的信号。我最近提供了新的证据，证明无脂肪物质（FFM）的代谢活动会促使人类进食，以确保关键组织和器官的能量需求得到满足。然而，将实况调查与饥饿联系起来的信号是未知的，我将利用这一研究金来查明这些信号。通过将FFM定位为食欲的关键特征，我的研究还提供了新的机会来了解食欲的变化如何对抗减肥。在能量限制期间增加饥饿和食物摄入是人们努力实现和维持减肥的关键原因之一。然而，饥饿的这些变化是不一致的;一些人报告饥饿增加，而另一些人则没有变化或饥饿减少。目前，我们还不能充分解释其中的原因。迄今为止，几乎没有人试图研究减肥过程中FFM的损失如何影响体重引起的食欲变化。通过建立如何以及为什么FFM损失促进食欲增加和食物摄入量后减肥，我将提供新的理解为什么人们不能保持减肥和促进新的策略，以对抗这些食欲的变化设计。目标：我的奖学金将开发一种新的人类食欲生物模型，将FFM及其相关的能量需求作为饥饿的决定因素。我将把这个模型应用到减肥的情况中，来解释食欲的变化是如何抵抗减肥的。为了实现这一点，我将：1。对肥胖成年人进行减肥研究，包括详细的身体成分、能量消耗和食欲的实验室测量，以及使用可穿戴腕戴式活动监测器（Fitbits）和每周体重（蓝牙秤）得出的食欲、食物摄入量、能量消耗的自由生活测量。2.检查FFM作为个体体重稳定时进食动力的新决定因素（即，在能量平衡）和减肥后，使用实验室和自由生活环境下的食物摄入量的客观措施。应用与益处：通过针对驱动而不是抑制饥饿的机制，我的研究将为健康和疾病中影响食欲的因素提供新的见解。在减肥过程中检查这些机制将为食欲变化如何对抗减肥提供基本的见解，促进针对这些变化的有针对性的干预措施的设计。量化减肥期间自由生活食物摄入和能量消耗的变化将确定营养或行为支持的最佳时机，以更好地为营养和公共卫生指南提供信息。通过识别将FFM与食物摄入联系起来的信号，我将为那些对食欲受损（衰老，癌症，糖尿病）感兴趣的人提供重要的临床相关性新见解。这也将为对体重控制感兴趣的药理学行业提供机会，通过确定新的靶点来阻断饮食驱动的特定机制。