Effects of negative energy balance on muscle mass regulation

骨骼肌是人体新陈代谢的关键。已经提出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引起的关注相对较少。神经内分泌因子网络紧密调节能量平衡和脂肪量。类似的神经内分泌网络可能有助于肌肉质量的调节。有意减肥（节食）总是会导致肌肉质量损失。我们假设，有意减肥修改负责任的调节神经内分泌网络。我们将分析有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行动，这是由于身体成分的修改。为了解决这些问题，我们将在60名绝经后妇女中进行一项随机对照减肥试验。我们将在减肥前、减肥期间和减肥后（体重稳定和体重恢复后）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。将包括详细的体内代谢表征，包括微透析、能量平衡、夹钳、MRI成像和使用靶向和无偏倚技术（如表达谱）对每名参与者的人肌管进行离体分析。这些分析将提高我们对肌肉质量的内分泌调节的理解，并可能提供新的内分泌或代谢靶点，以避免在减肥干预期间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，因为体重恢复不一定伴随着肌肉质量的恢复。此外，我们还将审查造成任何反效果的机制。

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.