1,3,7,9-四甲基尿酸激活SirT3/AMPK/ACC信号通路减少高脂饮食小鼠肝脏脂肪化  

Theacrine ameliorates high fat diet induced hepatic steatosis in mice via SirT3 /AMPK /ACC pathway

作　　者：徐军[1] 王国恩[2] 章时杰[3] 何蓉蓉[2] 栗原博[2] 秦书俭[1] 

机构地区：[1]辽宁中医药大学基础医学院,辽宁沈阳110032 [2]暨南大学中药及天然药物研究所,广东广州510632 [3]广州中医药大学临床药理所,广东广州510405

出　　处：《中国药理学通报》2014年第6期791-795,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81102485);广东省自然科学基金资助项目(No S2011040004893);辽宁省科技厅项目(No 201202129)

摘　　要：目的研究嘌呤生物碱1,3,7,9-四甲基尿酸(theacrine)对高脂饮食小鼠肝脏甘油三酯蓄积的影响,并进一步探讨其作用机制。方法 C57BL/6J小鼠高脂喂养17周诱导单纯性脂肪肝模型,连续6周给予theacrine后,分别对肝组织切片进行HE和苏丹IV染色,测定肝脏中甘油三酯(TG)水平,用Western blot法检测肝脏中SirT3蛋白表达、AMPK及ACC蛋白的磷酸化水平。应用compound C抑制HepG2细胞中AMPK磷酸化,检测theacrine干预后相关蛋白的表达。结果 Theacrine能减少高脂饮食小鼠肝脏中TG水平,改善肝脏脂肪变性状态,增加肝脏中SirT3蛋白表达及AMPK和ACC蛋白的磷酸化水平。抑制细胞内AMPK的磷酸化后,theacrine仍能激活SirT3,但抑制了ACC的磷酸化作用。结论 Theacrine对SirT3的激活不依赖于AMPK的激活,而对ACC的磷酸化依赖于AMPK的激活。其改善高脂饮食小鼠肝脏脂肪化的作用可能与激活SirT3/AMPK/ACC信号通路相关。Aim To investigate the effects and mecha-nisms of theacrine on high fat diet induced hepatic steatosis in mice. Methods The C57BL/6J mice were fed with high fat diet for consecutive 17 weeks to induce hepatic steatosis and given a treatment of theac-rine for 6 weeks. The liver sections were stained with H＆amp;E or Sudan IV, and hepatic TG was determined by commercial analysis kits. Expression of SirT3 and phosphorylation of AMPK and ACC were measured by Western blot. Compound C was used to inhibit the phosphorylation of AMPK in HepG2 cells, and the expressions of proteins were determined after the cells were treated with theacrine. Results Theacrine significantly decreased hepatic TG content and ameliora-ted hepatic steatosis in mice. Expression of SirT3 and phosphorylation of AMPK and ACC were up-regulated, respectively. And theacrine still could activate SirT3 and upregulate the phosphorylation of ACC whatever AMPK was inhibited. Conclusions The activation of ACC by theacrine depends on the phosphorylation of AMPK, but the activation of SirT3 by theacrine is in-dependent of the phosphorylation of AMPK. Theacrine ameliorates high fat diet induced hepatic steatosis in mice probably via SirT3/ AMPK/ ACC pathway.

关 键 词：Theacrine 嘌呤生物碱 高脂饮食 单纯性脂肪肝 SirT3 AMPK ACC 

分 类 号：R-332[医药卫生] R284.1