基于β3-AR/PKA/AMPK信号途径对米色脂肪的调控探讨芝麻酚治疗营养性肥胖症的作用及机制

增加米色脂肪的含量、线粒体功能及脂代谢，可增强能量消耗，是治疗营养性肥胖症的新思路。脂肪β3-AR/PKA/AMPK信号的激活，可能诱导米色脂肪生成、维持米色脂肪状态、增强线粒体功能及脂代谢；肝脏PKA/AMPK信号的激活，可能使FGF21增多，间接影响米色脂肪。最新报道及我们前期工作发现，芝麻酚具有减肥功效，但机制尚未明确。我们还发现芝麻酚可激活肝脏PKA/AMPK，且有报道提示芝麻酚保护神经、抗血栓等的机制可能与调控β-ARs、PKA相关。据此推测：芝麻酚可能激活脂肪β3-AR/PKA/AMPK信号，和/或肝脏PKA/AMPK信号，从而调控米色脂肪。我们首次提出：可围绕β3-AR/PKA/AMPK信号途径对米色脂肪的调控，从整体、组织、细胞及分子等多水平，探讨芝麻酚治疗营养性肥胖症的作用机制。本项目将为理解米色脂肪、从常见膳食中开发靶向性的治疗营养性肥胖症的功能因子，提供新的科学依据。

A novel strategy for the treatment of alimentary obesity is to enhance the content, mitochondrial function and lipid metabolism of beige fat, which can promote energy expenditure. The activation of the β3-AR/PKA/AMPK signal pathway in white fat may directly induce the beige adipogenesis, maintain the beige state, enhance mitochondrial function and lipid catabolism. The activation of the PKA/AMPK signal pathway in liver may increase the production and secretion of FGF21, which may indirectly regulate the beige fat. According to the latest reports and our preliminary experiment, sesamol might have the effects of anti-obesity, but the underlying mechanisms are still not clear. We also found that sesamol could enhance the hepatic PKA/AMPK pathway, and some studies revealed that the effects of sesamol on nerve protection and platelet agglutination reduction might relate to the regulation of β-ARs or PKA. We therefore speculate that sesamol may regulate the beige fat by activating the β3-AR/PKA/AMPK signal pathway of white fat, and/or the PKA/AMPK signal pathway of liver. Based on these, it is proposed for the first time that the anti-obesity effects of sesamol by directly and/or indirectly enhance the content, mitochondrial function and lipid metabolism of beige fat can be investigated around the β3-AR/PKA/AMPK signal pathway. In order to understand the beige fat and to investigate the functional factors for the treatment of alimentary obesity from the common dietary elements, the present study will explore the effects and mechanisms of sesamol from the aspects of holistic, histological, cellular and molecular levels. This study is of great theoretical and practical significance for the safe and effective prevention and treatment of human alimentary obesity and obesity-related diseases.