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

项目摘要 这项建议的目的是描述两种运动“强度剂量”对总胃促生长素的影响。 Ghrelin和Des-acyl Ghrelin在患有和不患有糖尿病前期的瘦和肥胖成年人中的作用。生长激素释放蛋白(Ghrelin，TG)参与 调节食欲、能量平衡、葡萄糖代谢和胰岛素敏感性。Ghrelin存在于血液中 以去酰基形式(DAG~78%的Tg)和酰化形式(AG~22%的Tg)。尽管没有那么丰富， AG具有多种促进能量储存的作用，包括刺激食欲、抑制胰岛素 从胰腺释放，并通过广泛表征的生长激素促分泌剂增加肥胖症 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，通过一种尚未确定的受体起作用。最优的 甘油三酯、甘油三酯和甘油三酯的比例尚不清楚。同样，需要有针对性的方法，以便能够有效地 操纵这些多肽以帮助预防和/或治疗肥胖症、代谢综合征、糖尿病前期 和2型糖尿病。运动为治疗胃促生长素失调提供了一种独特的治疗方法。 检查运动和胃促生长素释放的有限的动物和人体研究大多是模棱两可的，或者只是 文件Tg和/或单一形式(例如AG)的Ghrelin。由于DAG和AG可以协同作用， 对抗地，或具有独立作用，这些肽对运动的反应的量化是 了解运动对Ghrelin释放的作用以及运动诱导的Ghrelin对 全面的血糖调节和能量平衡。运动强度可能是关键，因为运动可以提高 运动后，乳酸水平会抑制AG和食欲。在这里，我们建议解决这一知识差距 通过定义急性运动强度，在乳酸阈值以上和以下的剂量，对TG，AG， 和DAG释放在患有和不患有糖尿病前期的瘦削和肥胖个体中。具体目标1：审查 运动强度对胃促生长素、胰岛素、血糖和自述食欲的影响。假设：更高 运动强度会对TG、AG、DAG、AG/DAG、胰岛素和血糖AUC产生不同的影响 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： 这是一个探索性的目标，使用回归建模来检查运动诱导的 Ghrelin对血糖、胰岛素和食欲的影响。假设：TG、AG、DAG和AG/DAG改变将 不同地预测糖代谢、胰岛素敏感性和食欲的变化。这些改动各不相同 按性别、肥胖程度、动静脉瘘和糖尿病前期。此试验/可行性应用程序的结果将通知 一份较大的意见书，定义了TG、AG和DAG的治疗运动目标，并审查了 运用精确运动处方技术进行个体化运动训练的效果观察 胃促生长素释放。

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.