随着人们生活水平的高，非酒精性脂肪肝、肥胖等代谢性疾病的发病率日 益增加[1]。Amp-dependent protein kinase (AMPK),是参与机体能量代谢调控的关键 激酶。之前研究显示，许多药物都以 AMPK 作为靶点来治疗肥胖等代谢性疾病 [2]。亚精胺，是一种多胺类化合物，在自然界中广泛存在。研究表明，亚精胺具有 促进长寿的作用，并且有强大的抗炎以及抗氧化效应，并且具有抗动脉粥样硬化 的作用[3, 4]。基于以上研究，我们出设想，亚精胺是否参与脂质代谢，减轻非酒 精性脂肪肝以及肥胖的症状。我们的研究发现，给高脂饮食喂养的肥胖小鼠腹腔 注射亚精胺(实验组)，与对照组(腹腔注射磷酸盐缓冲液)相比，其体重有所 下降，腹股沟皮下脂肪以及内脏脂肪含量均有所减少;并且逆转了肝脏脂肪变 性，小鼠肝细胞内甘油三酯以及总胆固醇含量降低;此外，亚精胺治疗明显改善 了高脂饮食诱导肥胖小鼠的葡萄糖耐量以及胰岛素耐量。体内外实验表明，亚精 胺增加了小鼠肝脏、肝细胞内 AMPK 的磷酸化程度，并且抑制了脂合成相关基因 的表达。我们猜想，亚精胺产生的这些效应可能是由于激活了能量代谢核心 AMPK。接着我们进一步分离了小鼠肝脏原代细胞进行实验，结果表明，在加入 AMPK 的抑制剂 Compound C 后，亚精胺的上述效应消失了。综上所述，亚精胺 通过激活 AMPK 的方式，降低了肝脏脂合成基因的表达量，进一步减轻高脂饮食 诱导的非酒精性脂肪肝症状，未来有可能作为治疗非酒精性脂肪肝的新药物 。

With the improvement of people's living standards, the incidence of metabolic diseases such as non-alcoholic fatty liver disease and obesity is increasing [1]. Amp-dependent protein kinase, AMPK, is a key kinase for energy metabolism in the body. Studies have shown that many drugs target AMPK to treat metabolic diseases such as obesity [2]. Spermine is a polyamine compound. Studies have shown that spermidine can promote longevity, and has strong anti- inflammatory and antioxidant effects, as well as anti-atherosclerosis[3, 4]. Based on the above studies, we hypothesized that whether spermidine is involved in lipid metabolism can further alleviate the symptoms of non-alcoholic fatty liver disease. In this study, treatment of high-fat diet-induced obesity (DIO) C57BL/6J mice with spermidine decreased body weight and subcutaneous and visceral fat content, reversed the apparent hepatosteatosis, and reduced hepatic intracellular and serum triglyceride and total cholesterol concentrations. Moreover, spermidine treatment improved glucose tolerance and insulin sensitivity in DIO mice. The mechanism studies indicated that spermidine indeed increased the phosphorylation of hepatic AMP-activated pro- tein kinase (AMPK), and inhibited the expression of lipogenic genes in vivo and in vitro. Moreover, these spermidine-mediated molecular effects were also abolished by compound C, an inhibitor of AMPK, in primary hepatocytes. In summary, spermidine protected against DIO-induced hepatosteatosis by decreasing lipogenic genes expression through an AMPK- mediated mechanism.