基于AMP-激活的蛋白激酶通路调控探讨辣椒素酯治疗营养性肥胖的作用机制

AMPK的激活可协助代谢通路刺激能量消耗增加，从而可安全有效的治疗营养性肥胖症及其相关疾病。以往研究发现：辣椒素可增加机体产热和能量消耗，减肥降脂，并具有潜在的治疗肥胖相关疾病的功效。辣椒素酯结构和功能与辣椒素相似，且不具辛辣口感，更具开发其生物学活性的价值。迄今对辣椒素酯减肥功能的研究尚少，结论尚不一致，作用机制仍不清楚。我们提出假说：辣椒素酯可能具有减肥降脂、刺激机体产热、增强能量消耗、减轻炎症等作用，这些与AMPK通路在机体中对能量代谢的调节一致，因此，辣椒素酯可能以AMPK为靶点发挥治疗营养性肥胖症的作用。本研究拟通过肥胖大鼠模型、高脂环境下的细胞模型，从动物整体、组织、细胞以及分子水平等多方面探讨辣椒素酯对糖脂代谢的影响，明确其减肥效果，探索作用机制及靶点。本研究将为从常见的膳食元素中探寻新的具有减肥功效的功能因子，建立安全有效的减少肥胖及其并发症发生的方法提供新的科学依据。

Activation of AMPK could assist metabolic pathway to increase energy consumption, which could treat alimentary obesity safely and effectually. Former studies confirmed that: Capsaicin could increase thermogenesis and energy consumption to reduce weight and fat, and it had potential effects to treat obese-related diseases. Capsinoids are nonpungent Capsaicin-related substances and seem to have similar effects to Capsaicin, so Capsinoids are more worthy for developing biological activity. So far, there are few studies on weight loss effect of Capsinoids, and the research conclusion is not consistent, the mechanisms are not clear. Thus we raised the hypothesis: Capsinoids may have the effects of weight and fat loss, increasing thermogenesis and energy consumption, and reducing inflammation. These are consistent to the regulations of energy metabolism by AMPK pathway. Therefor, AMPK may be the target of Capsinoids for therapy of alimentary obesity. This study will use the obesity rat model and cell model in high lipid environment to clarify the influence on the glucose and lipid metabolism and effects of weight loss by Capsinoids, to investigate the mechanism and target of it from the aspects of holistic, histological, cellular and molecular level. This stuy will provide new sicentific basis for exploiting new weight loss functional factors from common dietary elements, and for establishing safe and effective method for the treatment of alimentary obesity and obese-related diseases.