Effects of negative energy balance on muscle mass regulation

负能量平衡对肌肉质量调节的影响

• 批准号: 184034212
• 负责人: Professor Dr. Joachim Spranger
• 金额: --
• 依托单位: Medizinische Klinik für Endokrinologie und Stoffwechselmedizin (Diabetes und Ernährungsmedizin)
• 依托单位国家: 德国
• 项目类别: Clinical Research Units
• 财政年份: 2010
• 资助国家: 德国
• 起止时间: 2009-12-31 至 2015-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/184034212?language=en
• 关键词: Effects; negative; energy; balance; muscle

Skeletal muscle is pivotal to the body’s metabolism. Losses of skeletal muscle mass have been proposed to predict mortality. Oddly, the regulation of muscle mass itself has accrued relatively little attention. A network of neuro-endocrine factors tightly regulates energy balance and fat mass. An analogous neuro-endocrine network likely contributes to the regulation of muscle mass. Intentional weight loss (dieting) invariably leads to muscle mass losses. We hypothesize that intentional weight loss modifies the responsible regulatory neuro-endocrine network. We will analyze changes in muscle mass and function during and after intentional weight loss. We will dissociate effects of negative energy balance and those actions, which result from a modification of body composition. To address these topics, we will perform a randomized controlled weight reduction trial in 60 post-menopausal women. We will study the subjects before, during, and after weight reduction (with stable weight and after weight regain). Phenotyping will include a detailed analysis of potential endocrine parameters involved in the regulation of muscle mass. Detailed metabolic in-vivo characterization including microdialysis, energy balance, clamps, MRI imaging and ex-vivo analysis of human myotubes from each participant using targeted and unbiased technologies, such as expression profiling will be included. These analyses will improve our understanding of the endocrine regulation of muscle mass and may offer novel endocrine or metabolic targets to avoid the well known side effect of muscle mass reduction during weight loss interventions. We raise the provocative notion that short-term dieting (being clinical reality) could be detrimental, since weight regain is not necessarily accompanied by regain of muscle mass. Furthermore, we will examine the mechanisms responsible for any counterproductive effects.

骨骼肌对人体的新陈代谢至关重要。已经提出了骨骼肌质量的损失来预测死亡率。奇怪的是，肌肉质量本身的调节几乎没有引起关注。神经内分泌因子网络严格调节能量平衡和脂肪质量。类似的神经内分泌网络可能有助于调节肌肉质量。故意减肥（节食）总是会导致肌肉质量损失。我们假设故意减肥会改变负责任的调节性神经内分泌网络。我们将分析故意减肥期间和之后的肌肉质量和功能的变化。我们将分离负能量平衡的影响和由身体组成的修饰所致的作用。为了解决这些主题，我们将在60名绝经后妇女中进行随机控制的减肥试验。我们将在减轻体重（重量稳定，重新恢复后重量稳定）之前，期间和之后研究受试者。表型将包括对肌肉质量调节的潜在内分泌参数的详细分析。详细的代谢内表征包括微透析，能量平衡，夹具，MRI成像和对每个参与的人肌管的前体内分析，使用靶向和无偏见的技术，例如表达分析，例如表达分析。这些分析将提高我们对肌肉质量内分泌调节的理解，并可能提供新颖的内分泌或代谢靶标，以避免在体重减轻干预期间肌肉质量减少的副作用。我们提出了一个挑衅的注意，短期节食（临床现实）可能有害，因为重量不一定是通过重复肌肉质量来实现的。此外，我们将检查负责任何适得其反作用的机制。