Effects of Evoked Resistance Training and Testosterone after Spinal Cord Injury

脊髓损伤后诱发抗阻训练和睾酮的影响

• 批准号: 8279499
• 负责人: Ashraf Gorgey
• 金额: --
• 依托单位: VA VETERANS ADMINISTRATION HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-01 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8279499
• 关键词: Address; Adipose tissue; Ankle; Area; Area Under Curve; Attenuated; Biological Markers; Body Composition; Body fat; C-reactive protein; Carbohydrates; Cardiovascular Diseases; Chronic; Clinical; Complex; Deterioration; Dyslipidemias; Educational Status; Electric Stimulation; Electron Transport; Energy Metabolism; Energy-Generating Resources; Exercise; Extramural Activities; Fatty acid glycerol esters; Fiber; Funding; Glucose; Glucose Intolerance; Glucose Transporter; Goals; Health; Homeostasis; Hormones; Individual; Inflammatory; Injury; Insulin; Insulin Resistance; Insulin-Like Growth Factor I; Intervention; Intramuscular; Knee; Laboratories; Lead; Leg; Lipids; Lower Extremity; Mediating; Mentors; Mentorship; Metabolic; Metabolic Diseases; Methods; Mitochondria; Motor; Muscle; Muscle Cells; Muscle Fibers; Muscle Proteins; Non-Insulin-Dependent Diabetes Mellitus; Nonesterified Fatty Acids; Obesity; Outcome; PPAR gamma; Participant; Phenotype; Physiological Adaptation; Plasma; Population; Positioning Attribute; Proteins; Randomized; Replacement Therapy; Research; Research Design; Research Methodology; Research Personnel; Rest; Risk; SLC2A1 gene; Secondary to; Serum; Shoulder; Skeletal Muscle; Somatomedins; Spinal cord injury; Surface; Testosterone; Thigh structure; Training; Training Programs; Triglycerides; Tumor Necrosis Factor-alpha; Veterans; Visceral; Weight; Work; base; blood glucose regulation; cytokine; experience; glucose metabolism; improved; insulin sensitivity; lipid metabolism; muscle form; muscle hypertrophy; neuromuscular; oxidation; programs; protein expression; research study; response; strength training; testosterone replacement therapy; trend

DESCRIPTION Individuals with spinal cord injury (SCI) are at a lifelong risk of increasing obesity and several chronic metabolic disorders such as glucose intolerance, insulin resistance and dyslipidemia secondary to deterioration in body composition. Within few weeks of injury, there are significant decrease in whole body fat-free mass (FFM), particularly lower extremity skeletal muscle mass and subsequent increase in fat mass (FM). Resistance training (RT) is an important type of exercise that has been shown to induce positive physiological adaptations such as increasing lean mass and reducing metabolic disorders in other clinical populations. In a pilot work, we provided evidence that evoked RT using surface neuromuscular electrical stimulation (NMES) for knee extensor muscle group resulted in significant increase skeletal muscle cross-sectional area (CSA), reduction in % leg FM and a trend towards decrease in visceral adipose tissue (VAT) CSA. The favorable adaptations in body composition were associated with decrease in plasma insulin area under the curve and plasma triglycerides. We attributed the adaptations in body composition and metabolic profile to an associated increase in plasma insulin-like growth factor (IGF-1). We concluded that twelve weeks of evoked RT targeted towards evoking skeletal muscle hypertrophy could result in significant body composition and metabolic adaptations in individuals with SCI. It is unclear if a longer RT program greater than 12 weeks would provide additional benefits to veterans with SCI. It is also unknown whether enhancing the decline anabolic homeostasis by providing testosterone (T) replacement therapy (TRT) would reverse body composition and metabolic profile changes in veterans with SCI. The major research goal of this proposal is to investigate the effects of 16 weeks of evoked RT+TRT vs. TRT on body composition (muscle CSA, VAT, %FM) and the metabolic profiles (glucose and lipid metabolism) in individuals with motor complete SCI. To address this goal, surface NMES accompanied with ankle weights will be conducted twice weekly to exercise the knee extensor skeletal muscle groups from sitting position. After 4 weeks of delayed entry approach, participants (n =24) will be randomly assigned into RT+TRT (n =12) or TRT (n =12) groups. The TRT will be provided via transdermal T patches that will be alternated on both shoulders over the course of the study. We also propose to study the effects of detraining on body composition and metabolic profiles. The research plan includes three specific aims that were devised by the candidate and his mentors. Specific aim 1 will demonstrate the effects of NMES RT and/or Testosterone patches (Tp) on the CSA of thighs and legs skeletal muscle groups, percentage FFM, and the CSA of VAT, intramuscular fat and percentage FM after 16 weeks of training+Tp and 16 weeks of detraining. Specific aim 2 will determine the changes in metabolic milieu (resting energy expenditure, glucose homeostasis, lipid profile, free fatty acids, serum total and free testosterone and IGF-1), and cytokines (c-reactive protein, tumor necrosis factor alpha and IL-6 as inflammatory biomarkers) after 16 weeks of training+Tp and detraining. Specific aim 3 will determine if 16 weeks of evoked RT and Tp will increase GLUT-4 concentration, muscle IGF-1 and peroxisome-proliferator-activated receptor-gamma co-activator 1 (PGC-1) expressions, altered fiber type distribution and enhance the mitochondrial enzymatic activities (electron transport chain) compared to Tp only. PUBLIC HEALTH RELEVANCE: The goal of this proposal is to investigate the efficacy of a complimentary approach of evoked resistance training and testosterone replacement therapy on the changes in body composition and metabolic profile after SCI. The proposed method could become a recommended and simple intervention especially for individuals with limited access and poor tolerance to exercise. The rationale is based on the evidence that individuals with SCI experience decline in anabolic hormones which may be responsible for the deterioration in body composition and metabolic profiles and leads to increase obesity, type 2 diabetes mellitus, dyslipidemia and subsequently cardiovascular disease. The designed study will provide explanation to the adaptations in the energy source of the muscle cells in response to training. The completion of the proposed experiment will allow the candidate to compete as an independent research investigator.

描述 患有脊髓损伤（SCI）的个体有肥胖症增加的终生风险，几种慢性代谢疾病（例如葡萄糖不耐症，胰岛素抵抗和降低了人体组成恶化的血脂异常）的风险。在受伤后的几周内，全身无脂肪质量（FFM）显着下降，尤其是下肢骨骼肌质量，随后脂肪质量增加（FM）。耐药训练（RT）是一种重要的运动类型，已证明可以引起阳性的生理适应性，例如增加瘦肉质量和减少其他临床人群的代谢疾病。 在试点工作中，我们提供了证据表明，使用表面神经肌肉电刺激（NME）诱发了RT，用于膝关节伸肌群，导致骨骼肌横截面面积（CSA）显着增加，腿部FM％降低以及降低腿部FM的趋势以及降低了内脏脂肪组织（VAT）CSA的趋势。人体组成的有利适应与曲线和血浆甘油三酸酯下血浆胰岛素区域的减少有关。我们将身体组成和代谢谱的适应性归因于血浆胰岛素样生长因子（IGF-1）的相关增加。我们得出的结论是，针对诱发骨骼肌肥大的诱发的RT的十二周可能会导致SCI患者的身体组成和代谢适应性显着。 目前尚不清楚较长的RT计划是否会为SCI的退伍军人提供额外的好处。还尚不清楚通过提供睾丸激素（T）替代疗法（TRT）来增强合成代谢稳态的下降是否会逆转SCI退伍军人的身体成分和代谢变化。该提案的主要研究目的是研究诱发的RT+TRT与TRT对人体组成（肌肉CSA，增值税，％FM）的影响以及具有运动完整科学的个体中的代谢谱（葡萄糖和脂质代谢）。为了解决这个目标，将每周两次进行表面NME伴随着脚踝重量，以从坐姿锻炼膝盖伸肌骨骼肌群。在进入延迟入学方法4周后，参与者（n = 24）将随机分配到RT+TRT（n = 12）或TRT（n = 12）组中。 TRT将通过在研究过程中在两个肩膀上交替的经皮贴片提供。我们还建议研究损失对人体成分和代谢谱的影响。研究计划包括候选人及其导师设计的三个具体目标。具体的目标1将证明NMES RT和/或睾丸激素斑块（TP）对大腿和腿部骨骼肌群的CSA，FFM百分比以及VAT的CSA，肌肉内脂肪和FM的CSA，在训练+TP+TP和16周后的16周后FM。具体目标2将确定代谢环境的变化（静息能量消耗，葡萄糖稳态，脂质谱，游离脂肪酸，血清总和至关重要的睾丸激素和IGF-1）以及细胞因子（C反应蛋白，肿瘤坏死因子alpha alpha alpha和IL-6作为炎症性生物标志物作为炎症性生物标志物）在16周后培训+TP和培训。具体的目标3将确定16周的诱发RT和TP是否会增加GLUT-4浓度，肌肉IGF-1和过氧化物酶体增生剂激活的受体 - 伽玛共激活剂1（PGC-1）表达式，纤维类型的变化，并改变了线粒体酶活性（电子传输链）与TP相比。 公共卫生相关性： 该提案的目的是研究诱发抗药性训练和睾丸激素替代疗法的免费方法对SCI后身体成分和代谢特征的变化的疗效。提出的方法可能成为推荐和简单的干预措施，特别是对于有限且耐受性耐受性的人。理由是基于证据表明，SCI经验的个体经历下降代谢激素的下降，这可能导致人体组成和代谢谱的恶化，并导致肥胖，2型糖尿病，血脂异常和随后的心血管疾病。该设计的研究将为训练的肌肉细胞能量来源的适应来提供解释。拟议的实验的完成将使候选人能够作为独立研究研究者竞争。