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: 8495810
• 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/8495810
• 关键词: Address; Adipose tissue; Ankle; Area; Area Under Curve; Biological Markers; Body Composition; Body fat; Cardiovascular Diseases; Chronic; Clinical; Deterioration; Dyslipidemias; Electric Stimulation; Electron Transport; Energy Metabolism; Energy-Generating Resources; Exercise; Fatty acid glycerol esters; Fiber; Glucose Intolerance; Goals; Homeostasis; Hormones; Individual; Inflammatory; Injury; Insulin; Insulin Resistance; Insulin-Like Growth Factor I; Interleukin-6; Intervention; Intramuscular; Knee; Leg; Lipids; Lower Extremity; Mentors; Metabolic; Metabolic Diseases; Methods; Mitochondria; Motor; Muscle; Muscle Cells; Non-Insulin-Dependent Diabetes Mellitus; Nonesterified Fatty Acids; Obesity; PPAR gamma; Participant; Physiological Adaptation; Plasma; Population; Positioning Attribute; Proteins; Randomized; Replacement Therapy; Research; Research Design; 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; lipid metabolism; muscle form; muscle hypertrophy; neuromuscular; 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.

描述 脊髓损伤 (SCI) 患者终生面临肥胖和多种慢性代谢紊乱的风险，如葡萄糖耐受不良、胰岛素抵抗和身体成分恶化继发的血脂异常。受伤后几周内，全身去脂质量（FFM）显着下降，尤其是下肢骨骼肌质量，随后脂肪质量（FM）增加。阻力训练（RT）是一种重要的运动类型，已被证明可以在其他临床人群中诱导积极的生理适应，例如增加瘦体重和减少代谢紊乱。 在一项试点工作中，我们提供的证据表明，使用表面神经肌肉电刺激 (NMES) 对膝伸肌群进行诱发 RT 可显着增加骨骼肌横截面积 (CSA)、腿部 FM 百分比降低以及内脏肌力下降的趋势脂肪组织 (VAT) CSA。身体成分的有利适应与血浆胰岛素曲线下面积和血浆甘油三酯的减少有关。我们将身体成分和代谢特征的适应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 12 周诱发 RT 可能会导致 SCI 患者发生显着的身体成分和代谢适应。 目前尚不清楚超过 12 周的较长 RT 计划是否会给患有 SCI 的退伍军人带来额外的好处。目前尚不清楚通过提供睾酮 (T) 替代疗法 (TRT) 来增强合成代谢稳态下降是否会逆转 SCI 退伍军人的身体成分和代谢特征变化。本提案的主要研究目标是调查 16 周诱发 RT+TRT 与 TRT 对运动完全性个体的身体成分（肌肉 CSA、VAT、%FM）和代谢特征（葡萄糖和脂质代谢）的影响SCI。为了实现这一目标，每周两次配合踝关节重量的表面 NMES，以从坐姿锻炼膝关节伸肌骨骼肌群。经过 4 周的延迟进入方法后，参与者 (n = 24) 将被随机分配到 RT+TRT (n = 12) 或 TRT (n = 12) 组。 TRT 将通过透皮 T 贴片提供，在研究过程中将在双肩上交替贴片。我们还建议研究停止训练对身体成分和代谢特征的影响。该研究计划包括由候选人及其导师制定的三个具体目标。具体目标 1 将展示 NMES RT 和/或睾酮贴片 (Tp) 对训练 16 周+Tp 后大腿和腿部骨骼肌群的 CSA、FFM 百分比以及 VAT、肌内脂肪和 FM 百分比的 CSA 的影响以及16周的停训。具体目标 2 将确定代谢环境（静息能量消耗、葡萄糖稳态、血脂、游离脂肪酸、血清总睾酮和游离睾酮以及 IGF-1）和细胞因子（C 反应蛋白、肿瘤坏死因子 α 和 IL）的变化-6 作为炎症生物标志物）16 周训练+Tp 和停止训练后。具体目标 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 和过氧化物酶体增殖物激活受体 - γ 共激活剂 1 (PGC-1) 表达、改变纤维类型分布并增强线粒体酶活性（电子传递链）与仅 Tp 相比。