课题组有关“镁与代谢综合征关系”的研究得到国际认可，结合前期“低氧训练显著改善糖脂代谢”研究结果，首次证实：血清镁浓度高低直接影响低氧训练减控体重效果。但镁摄入和低氧训练交互作用分子机制未明。我们假设：低氧训练可增加PGC-1α、HIF-1α产生，有利于激活PPAR-γ；镁可促进PPAR-γ的磷酸化。因此，两者分别从质和量层面激活PPAR-γ，进而改变从脂肪组织释放入血的信号分子浓度，改善肝脏和肌肉中胰岛素的敏感性。本研究应用分子生物学实验技术，观察镁补充结合低氧训练对肥胖小鼠脂肪组织、肝、骨骼肌PPARs及糖脂代谢的影响，并使用脂肪组织PPAR-γ基因敲除进行验证。该研究将填补国内外空白，对阐明镁补充与低氧训练对糖脂代谢交互作用的分子机制意义重大，并为低氧训练结合营养措施减控体重的"绿色"方法提供理论基础，为肥胖相关疾病的防治提供新思路。

Our previous study of magnesium intake and the risk of metabolic syndrome has been recognized internationally. As a result, a patent application of magnesium fortified sports drink is currently underway. Also, our previous study indicates that hypoxic training significantly improves glucose and lipid metabolism. In addition, our preliminary data suggest a synergistic effect of serum magnesium levels and hypoxic training on weight loss. However, the molecular mechanism of this joint effect is unknown. Studies suggest that the three ‘lipid-sensing’ peroxisome proliferator–activated receptors (PPAR-α, PPAR-γ and PPAR-δ) regulate diverse aspects of lipid and glucose homeostasis. Thus, we hypothesize that the joint effect of magnesium supplementation and hypoxic training on weight loss are mediated by modulating PPARs. Hypoxic training increases the production of PGC-1α and HIF-1α and facilitates PPAR-γ activation, while magnesium supplementation promotes PPAR-γ phosphorylation. After the activation of PPARs, PPAR-γ alters the release of signaling molecules from fat, including leptin, tumor necrosis factor-α (TNF-α), resistin and adiponectin, which through serum transport have far-reaching metabolic effects in other tissues. Activation of this metabolic pathway improves insulin sensitivity. At the same time, PPAR-α and PPAR-δ will promote fatty acid oxidation and insulin sensitivity in muscles and the liver. The proposed study aims to determine the joint effect of magnesium supplementation and hypoxic training on glucose and lipid metabolism in high-fat-diet induced obese mice using the state of the art techniques such as co-immunoprecipitation, Western blot, and liquichip, and PPAR-γ knockout. Findings from the proposed study may be helpful to identify an optimal way for weight control, and ultimately prevention and therapy of obesity and diabetes.