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

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):锻炼是许多与肥胖相关的代谢并发症(包括胰岛素抵抗)成功管理的关键组成部分。重要的是,耐力运动训练的许多有益的代谢作用归因于最近的运动会,而不是由长期训练或改善“适应性”的适应。因此,应针对肥胖,耐胰岛素的患者进行生活方式干预措施,以优化最近运动会的代谢作用。然而,尚不清楚急性运动的“剂量”(即提高肥胖中胰岛素敏感性所需的强度,持续时间,消耗的强度,消耗的能量),而导致这种改进的机制仍然很少了解。在肥胖个体中发现的过量脂肪酸的可用性在很大程度上是抑制胰岛素敏感性的原因。这些脂肪酸在心肌细胞中的“分割”朝着细胞内脂肪酸中间体的氧化,储存或积累(例如,神经酰胺,二酰基甘油酸,脂肪酰基酰基辅酶A)以及产生的促炎途径的激活(例如我们的工作假设是:尽管脂肪酸的可用性和吸收持续升高,但第二天,在肥胖成年人中进行一次运动将提高胰岛素敏感性,部分原因是急性运动会将脂肪酸从脂肪酸中间体的积累中分开,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%vo2peak)和单个运动疗法对胰岛素敏感性和肌肉脂肪酸代谢的不同水平的能量消耗(200 vs 350kcal)的影响,在肥胖成年人中进行了运动后的第二天[特定的目标#1]。我们假设在锻炼过程中以50%和65%的vo2peak(分别〜60和〜45分钟的锻炼)在锻炼过程中花费350 kcal,并且在65%vo2peak(锻炼的65%)锻炼过程中花费200 kcal(锻炼的30分钟)足以在脂肪酸分配过程中改变脂肪酸,并减少50次肌肉的疾病,但可以改善胰岛素的影响,但持久性持久性良好,但持久性持久性持久性,但持久性良好,但是持续性良好,但要改善脂肪含量,但要改善脂肪酸的影响,但要改善脂肪酸的影响,但要改善脂肪酸的影响。 Vo2peak(锻炼的40分钟)不会。为了更明确地测试运动诱导的脂肪酸分配改变对胰岛素敏感性的贡献,我们将评估特定目标1中发现的最小运动“剂量”是否可以防止肥胖成年人中脂肪酸诱导的胰岛素抵抗[特定目标2]。最后,我们将检查低剂量运动的累积作用(在50%VO2PEAK时进行40分钟的运动)在几天,几周和几个月内对胰岛素敏感性,脂肪酸分配以及促炎性途径的激活[特定AIM#3]。这些研究的结果将大大提高我们对肥胖运动后胰岛素作用和脂肪酸分配的调节的理解。此外,这些发现将为制定生活方式计划的有价值的信息提供宝贵的信息,旨在最大程度地利用肥胖的胰岛素抵抗患者,每次运动的主要代谢益处。

项目成果

期刊论文数量(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。
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

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:
Nutrition, Exercise and phenotype Testing Core
营养、运动和表型测试核心
  • 批准号:
    10190911
  • 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:
    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:
    8249886
  • 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:
Nutrition, Exercise and phenotype Testing Core
营养、运动和表型测试核心
  • 批准号:
    10425295
  • 财政年份:
    2010
  • 资助金额:
    $ 30.77万
  • 项目类别:
Nutrition, Exercise and phenotype Testing Core
营养、运动和表型测试核心
  • 批准号:
    10656191
  • 财政年份:
    2010
  • 资助金额:
    $ 30.77万
  • 项目类别:

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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
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Insulin sensitivity and fatty acid partitioning in skeletal muscle after exercise
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