Modulation of Ghrelin Release by Exercise Intensity: The Role of Obesity and Prediabetes Status

运动强度对生长素释放肽的调节：肥胖和糖尿病前期状态的作用

• 批准号: 10661601
• 负责人: Arthur Weltman
• 金额: $ 32.3万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-05 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10661601
• 关键词: Abdomen; Acute; Acylation; Address; Affect; American; Animals; Appetite Regulation; Attenuated; Biological; Blood; Complex; Desire for food; Development; Disease; Dose; Dual-Energy X-Ray Absorptiometry; Elderly; Energy Metabolism; Exercise; Fatty acid glycerol esters; Female; Glucose; Goals; Health; Human; Impaired fasting glycaemia; Insulin; Insulin Resistance; Knowledge; Mediating; Medical Care Costs; Medicine; Metabolic; Metabolic syndrome; Modeling; Non-Insulin-Dependent Diabetes Mellitus; OGTT; Obesity; Outcome; Pancreas; Patient Self-Report; Peptides; Peripheral; Phenotype; Prediabetes syndrome; Prevention; Risk; Role; Somatotropin; Techniques; Testing; Therapeutic; Therapeutic exercise; Thinness; Tissues; Training Programs; United States; Visceral fat; Visit; adult obesity; blood glucose regulation; des-n-octanoyl ghrelin; design; energy balance; exercise intensity; exercise prescription; exercise training; fasting glucose; ghrelin; glucose metabolism; growth hormone secretagogue receptor; impaired glucose tolerance; improved; increased appetite; individual response; insulin secretion; insulin sensitivity; male; obese person; obesity risk; obesity treatment; receptor; response; sex

Project Summary The goal of this proposal is to characterize the effects of two exercise “intensity doses” on total ghrelin, acyl ghrelin, and des-acyl ghrelin in lean and obese adults with and without prediabetes. Ghrelin (TG) is involved in the regulation of appetite, energy balance, glucose metabolism and insulin sensitivity. Ghrelin exists in the blood in a des-acyl form (DAG ~78% of TG), and in an acylated form (AG ~22% of TG). Despite being less abundant, AG is has multiple actions that promote energy storage, including stimulation of appetite, inhibition of insulin release from the pancreas, and increases in adiposity via a widely characterized growth hormone secretagogue receptor. Conversely, DAG often opposes AG promoting negative energy balance (appetite suppression and reduced fat mass (FM)) and improving insulin sensitivity, acting through a receptor not yet identified. The optimal ratios of TG, DAG, and AG are not clear. Likewise, there is a need for targeted approaches that can effectively manipulate these peptides to aid in the prevention and/or treatment of obesity, metabolic syndrome, prediabetes and type 2 diabetes. Exercise provides a unique therapeutic approach in the treatment of dysregulated ghrelin. Limited animal and human studies examining exercise and ghrelin release are mostly equivocal or only document TG and/or a single (e.g. AG) form of ghrelin. As DAG and AG can act synergistically, antagonistically, or have independent effects, the quantification of these peptides in response to exercise is critical to understanding the role of exercise on ghrelin release and ghrelin's exercise induced influence on overall glucose regulation and energy balance. Exercise intensity may be key, as exercise that elevates levels of lactate suppress AG and appetite post exercise. Here we propose to address this gap in knowledge by defining the role of acute exercise intensity, at doses above and below the lactate threshold, on TG, AG, and DAG release in lean and obese individuals with and without prediabetes. Specific Aim 1: Examine effects of exercise intensity on ghrelin, insulin, glucose and self-reported appetite. Hypothesis: Higher exercise intensity will result in differential effects on TG, AG, DAG, AG/DAG, insulin, and glucose AUC's, and appetite; affected by sex, obesity, abdominal visceral fat (AVF), and prediabetes status. Specific Aim 2: This is an exploratory aim using regression modeling to examine exercise-induced changes in ghrelin on glucose, insulin and appetite. Hypothesis: TG, AG, DAG and AG/DAG alterations will differentially predict changes in glucose metabolism, insulin sensitivity, and appetite. These alterations vary by sex, levels of obesity, AVF, and prediabetes. Results from this pilot/feasibility application will inform a larger submission that defines therapeutic exercise targets for TG, AG, and DAG, and examines the effects of individualized exercise training using precision exercise prescription techniques on ghrelin release.

项目摘要 该提案的目的是表征两种运动“强度剂量”对总生长素蛋白的影响 在有和没有前糖尿病前的瘦肉和肥胖的成年人中，生长素释放肽和Des-acyl ghrelin。 Ghrelin（TG）参与 食欲，能量平衡，葡萄糖代谢和胰岛素敏感性的调节。血液中存在于血液中 以DES-acyl形式（tg的78％）和酰基形式（Tg的Ag约22％）。尽管不那么丰富，但 AG具有多种促进能量储存的动作，包括刺激食欲，抑制胰岛素 从胰腺释放，并通过广泛特征的成长牛gogue蛋 受体。相反，DAG经常反对AG促进负能量平衡（抑制食欲和 减少脂肪质量（FM））和改善胰岛素敏感性，该敏感性通过尚未鉴定的受体作用。最佳 TG，DAG和AG的比率尚不清楚。同样，需要有效的目标方法 操纵这些肽以帮助预防和/或治疗肥胖，代谢综合征，前糖尿病 和2型糖尿病。运动为治疗失调的生长素素提供了独特的治疗方法。 有限的动物和人类研究检查运动和生长素释放的释放大部分是等效的，或者仅是 文档TG和/或生长素的单一（例如Ag）形式。由于DAG和AG可以协同行动， 拮抗或具有独立效应，这些肽对运动的响应是 了解运动对生长素释放的作用至关重要 总体葡萄糖调节和能量平衡。运动强度可能是关键，因为锻炼会提升 锻炼后的鞋底抑制Ag和食欲。在这里，我们建议在知识上解决这一差距 通过定义急性运动强度的作用，以鞋底阈值上方和下方的剂量在TG，Ag， 并在具有和没有前糖尿病前的精益和肥胖的个体中释放DAG。特定目标1：检查 运动强度对生长素蛋白，胰岛素，葡萄糖和自我报告的食欲的影响。假设：更高 运动强度将对TG，AG，DAG，AG/DAG，胰岛素和葡萄糖AUC产生不同的影响，并且 食欲;受性别，肥胖，腹部内脏脂肪（AVF）和糖尿病前期状态的影响。具体目标2： 这是使用回归建模来检查锻炼引起的变化的探索目的 葡萄糖，胰岛素和食欲的生长素素。假设：TG，AG，DAG和AG/DAG改变将 差异预测葡萄糖代谢，胰岛素敏感性和食欲的变化。这些改变的变化 通过性别，肥胖，AVF和糖尿病的水平。该试点/可行性申请的结果将告知 较大的提交定义TG，AG和DAG的热运动目标，并检查 使用精确锻炼处方技术对个性化运动训练的影响 Ghrelin释放。

项目成果

The effect of acute exercise on pre-prandial ghrelin levels in healthy adults: A systematic review and meta-analysis.

• DOI: 10.1016/j.peptides.2021.170625
• 发表时间: 2021-11
• 期刊: PEPTIDES
• 影响因子: 3
• 作者: Anderson, Kara C.;Zieff, Gabriel;Paterson, Craig;Stoner, Lee;Weltman, Arthur;Allen, Jason D.
• 通讯作者: Allen, Jason D.