Insulin sensitivity and fatty acid partitioning in skeletal muscle after exercise
运动后骨骼肌中的胰岛素敏感性和脂肪酸分配
基本信息
- 批准号:8640925
- 负责人:
- 金额:$ 30.77万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2010
- 资助国家:美国
- 起止时间:2010-04-13 至 2015-09-30
- 项目状态:已结题
- 来源:
- 关键词:AcuteAcyl Coenzyme AAdultBody Weight decreasedCeramidesDevelopmentDoseEducational StatusEnergy MetabolismExerciseFatty AcidsHealth BenefitHeparinIndividualInflammatoryInfusion proceduresInsulinInsulin ResistanceJUN geneLife StyleLipidsMeasuresMediatingMediator of activation proteinMetabolicMuscleMuscle CellsObesityPathway interactionsPatientsPhosphorylationPlasmaRegulationSerineSkeletal MuscleStressTestingTrainingTraining ProgramsWorkfatty acid metabolismfitnesshuman NFIB proteinimprovedinflammatory markerinsulin sensitivitykinase inhibitorlifestyle interventionobesity treatmentoxidationpreventprogramspublic health relevanceresponsestemstress-activated protein kinase 1uptake
项目摘要
DESCRIPTION (provided by applicant): Exercise is a key component of the successful management of many obesity-related metabolic complications, including insulin resistance. Importantly, many of the beneficial metabolic effects of endurance exercise training are attributed to the most recent exercise session(s), rather than to adaptations resulting from prolonged training, or to improved "fitness", per se. Therefore, lifestyle interventions for obese, insulin resistant patients should be tailored to optimize the metabolic effects of the most recent exercise session(s). However, the "dose" of acute exercise (i.e., intensity, duration, energy expended) necessary to improve insulin sensitivity in obesity is not known, and the mechanisms responsible for this improvement are still poorly understood. The excessive fatty acid availability found in obese individuals is largely responsible for their suppressed insulin sensitivity. "Partitioning" of these fatty acids within the myocyte toward oxidation, storage, or accumulation of intracellular fatty acid intermediates (e.g., ceramide, diacylglyceride, fatty acyl-CoA), and the resultant activation of pro-inflammatory pathways (e.g., c-jun NH2-terminal kinase (JNK)) mediate this response. Our working hypothesis is: A single session of exercise in obese adults will improve insulin sensitivity the next day despite a persistent elevation in fatty acid availability and uptake, in part because acute exercise will partition fatty acids away from accumulation of fatty acid intermediates, and thereby reduce the activation of pro-inflammatory pathways. We will first compare the effect of different exercise intensities (50% vs. 65% VO2peak) and different levels of energy expenditure (200 vs 350kcal) of a single exercise session on insulin sensitivity and muscle fatty acid metabolism measured the day after exercise in obese adults [Specific Aim #1]. We hypothesize that expending 350 kcal during exercise at both 50% and 65% VO2peak (~60 and ~45 min of exercise, respectively), as well as expending 200 kcal during exercise at 65% VO2peak (~30min of exercise) will be sufficient to alter fatty acid partitioning, reduce pro-inflammatory stress, and thereby improve insulin sensitivity the next day, but expending 200 kcal during exercise at 50% VO2peak (~40min of exercise) will not. To more definitively test the contribution of exercise-induced alterations in fatty acid partitioning on insulin sensitivity we will assess whether the minimum "dose" of exercise found in Specific Aim #1 protects against fatty acid-induced insulin resistance in obese adults [Specific Aim #2]. Finally, we will examine the cumulative effect of low doses of exercise (40 min of exercise at 50% VO2peak) performed over days, weeks, and months on insulin sensitivity, fatty acid partitioning, and activation of pro-inflammatory pathways [Specific Aim #3]. Findings from these studies will vastly improve our understanding about the regulation of insulin action and fatty acid partitioning after exercise in obesity. Moreover, these findings will provide valuable information for the development of lifestyle programs aimed at maximizing the key metabolic benefits of each exercise session in obese, insulin resistant patients.
描述(由申请人提供):运动是成功管理许多肥胖相关代谢并发症的关键组成部分,包括胰岛素抵抗。重要的是,耐力运动训练的许多有益代谢作用归因于最近的运动,而不是由于长时间训练产生的适应,或者是“健康”本身的改善。因此,对肥胖、胰岛素抵抗患者的生活方式干预应量身定制,以优化最近一次运动的代谢效果。然而,改善肥胖患者胰岛素敏感性所需的急性运动“剂量”(即强度、持续时间、能量消耗)尚不清楚,对这种改善的机制也知之甚少。在肥胖人群中发现的过量脂肪酸是他们胰岛素敏感性被抑制的主要原因。这些脂肪酸在肌细胞内向氧化、储存或细胞内脂肪酸中间体(如神经酰胺、二酰基甘油酯、脂肪酰基辅酶a)的积累“分配”,以及由此产生的促炎途径(如c-jun nh2末端激酶(JNK))的激活介导了这一反应。我们的工作假设是:尽管脂肪酸的可用性和摄取持续升高,但肥胖成年人的单次运动将改善第二天的胰岛素敏感性,部分原因是急性运动将脂肪酸从脂肪酸中间体的积累中分离出来,从而减少促炎途径的激活。我们将首先比较不同运动强度(50% vs 65% vo2峰值)和不同能量消耗水平(200 vs 350kcal)对肥胖成年人运动后第二天测量的胰岛素敏感性和肌肉脂肪酸代谢的影响[具体目标#1]。我们假设在50%和65% vo2峰值(分别为~60和~45分钟)运动时消耗350千卡,以及在65% vo2峰值(~30分钟)运动时消耗200千卡,足以改变脂肪酸分配,减少促炎应激,从而改善第二天的胰岛素敏感性,但在50% vo2峰值(~40分钟)运动时消耗200千卡则不会。为了更明确地测试运动引起的脂肪酸分配改变对胰岛素敏感性的贡献,我们将评估在特定目标#1中发现的最小运动“剂量”是否可以保护肥胖成人免受脂肪酸引起的胰岛素抵抗[特定目标#2]。最后,我们将研究在数天、数周和数月内进行低剂量运动(在50% vo2峰值时运动40分钟)对胰岛素敏感性、脂肪酸分配和促炎途径激活的累积效应[Specific Aim #3]。这些研究的发现将极大地提高我们对肥胖运动后胰岛素作用和脂肪酸分配调节的理解。此外,这些发现将为制定生活方式计划提供有价值的信息,这些计划旨在最大限度地提高肥胖、胰岛素抵抗患者每次锻炼的关键代谢益处。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Jeffrey F Horowitz其他文献
Cycling efficiency is related to the percentage of type I muscle fibers.
骑行效率与I型肌纤维的百分比有关。
- DOI:
- 发表时间:
1992 - 期刊:
- 影响因子:4.1
- 作者:
E. Coyle;L. Sidossis;Jeffrey F Horowitz;J. Beltz - 通讯作者:
J. Beltz
Load and Velocity of Contraction Influence Gross and Delta Mechanical Efficiency
负载和收缩速度影响总机械效率和增量机械效率
- DOI:
10.1055/s-2007-1021289 - 发表时间:
1992 - 期刊:
- 影响因子:2.5
- 作者:
L. Sidossis;Jeffrey F Horowitz;E. Coyle - 通讯作者:
E. Coyle
Jeffrey F Horowitz的其他文献
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{{ truncateString('Jeffrey F Horowitz', 18)}}的其他基金
Exercise effects on adipose tissue morphology, metabolic function, and metabolic health with weight loss and weight regain in obesity
运动对肥胖患者体重减轻和体重恢复的脂肪组织形态、代谢功能和代谢健康的影响
- 批准号:
10535669 - 财政年份:2022
- 资助金额:
$ 30.77万 - 项目类别:
Exercise effects on adipose tissue morphology, metabolic function, and metabolic health with weight loss and weight regain in obesity
运动对肥胖患者体重减轻和体重恢复的脂肪组织形态、代谢功能和代谢健康的影响
- 批准号:
10775266 - 财政年份:2022
- 资助金额:
$ 30.77万 - 项目类别:
Exercise effects on adipose tissue morphology, metabolic function, and metabolic health with weight loss and weight regain in obesity
运动对肥胖患者体重减轻和体重恢复的脂肪组织形态、代谢功能和代谢健康的影响
- 批准号:
10684756 - 财政年份:2022
- 资助金额:
$ 30.77万 - 项目类别:
Insulin sensitivity and fatty acid partitioning in skeletal muscle after exercise
运动后骨骼肌中的胰岛素敏感性和脂肪酸分配
- 批准号:
9197979 - 财政年份:2010
- 资助金额:
$ 30.77万 - 项目类别:
Insulin sensitivity and fatty acid partitioning in skeletal muscle after exercise
运动后骨骼肌中的胰岛素敏感性和脂肪酸分配
- 批准号:
9029455 - 财政年份:2010
- 资助金额:
$ 30.77万 - 项目类别:
Insulin sensitivity and fatty acid partitioning in skeletal muscle after exercise
运动后骨骼肌中的胰岛素敏感性和脂肪酸分配
- 批准号:
8453447 - 财政年份:2010
- 资助金额:
$ 30.77万 - 项目类别:
Insulin sensitivity and fatty acid partitioning in skeletal muscle after exercise
运动后骨骼肌中的胰岛素敏感性和脂肪酸分配
- 批准号:
8249886 - 财政年份:2010
- 资助金额:
$ 30.77万 - 项目类别:
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