Effects of negative energy balance on muscle mass regulation

骨骼肌是人体新陈代谢的关键。骨骼肌量的减少已被提出用来预测死亡率。奇怪的是，肌肉质量本身的调节相对较少受到关注。神经内分泌因子网络严密地调节能量平衡和脂肪量。一个类似的神经-内分泌网络可能有助于肌肉质量的调节。刻意的减肥(节食)总是会导致肌肉质量的下降。我们假设，有意的减肥改变了负责任的神经-内分泌网络。我们将分析在故意减肥期间和之后肌肉质量和功能的变化。我们将分离负能量平衡的影响和那些由于身体成分改变而产生的行为。为了解决这些问题，我们将对60名绝经后妇女进行随机对照减肥试验。我们将在减重前、减重期间和减重后(稳定体重和恢复体重后)对受试者进行研究。表型分析将包括对参与肌肉质量调节的潜在内分泌参数的详细分析。详细的体内代谢特征，包括微透析、能量平衡、钳夹、磁共振成像和使用有针对性和无偏见的技术(如表达谱分析)对每个参与者的人体肌管进行体外分析。这些分析将提高我们对肌肉质量内分泌调节的理解，并可能提供新的内分泌或代谢靶点，以避免在减肥干预过程中肌肉质量减少的众所周知的副作用。我们提出了一个挑衅性的概念，即短期节食(临床现实)可能是有害的，因为体重恢复并不一定伴随着肌肉质量的恢复。此外，我们将研究产生任何适得其反效果的机制。

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.