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: 10279846
• 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 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10279846
• 关键词: Abdomen; Acute; 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; base; 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; 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.

项目总结