Caffeine ameliorates high energy diet-induced hepatic steatosis: sirtuin 3 acts as a bridge in the lipid metabolism pathway.
Caffeine ameliorates high energy diet-induced hepatic steatosis: sirtuin 3 acts as a bridge in the lipid metabolism pathway.
复制标题
DOI：
10.1039/c5fo00247h
复制
发表时间：
2015-08
期刊：
影响因子：
6.1
通讯作者：
Shi-Jie Zhang;Yi-Fang Li;Guo-En Wang;Rui-Rong Tan;Bun Tsoi;Gao-Wei Mao;Yu-jia Zhai;Ling-Fang Cao;Min Chen;H. Kurihara;Qi Wang;Rong-Rong He-Rong
中科院分区：
文献类型：
--
作者：
Shi-Jie Zhang;Yi-Fang Li;Guo-En Wang;Rui-Rong Tan;Bun Tsoi;Gao-Wei Mao;Yu-jia Zhai;Ling-Fang Cao;Min Chen;H. Kurihara;Qi Wang;Rong-Rong He-Rong
含咖啡因食物对非酒精性脂肪性肝病（NAFLD）的有益作用已被广泛报道。本研究的目的是探讨咖啡因对肝脂肪变性的影响。将C57BL/6小鼠随机分为正常日粮组和高能日粮组。通过灌胃给HED小鼠咖啡因。测量体重、肝脏脂质和肝脏损伤。同时，在油酸处理的HepG2细胞中，在咖啡因孵育前分别处理cAMP、SIRT3或AMPK抑制剂。SIRT3进一步被siRNA沉默以证实结果。咖啡因显著降低了hed处理小鼠肝脏的脂肪组织质量、脂质、ALT和AST水平。咖啡因增加了ADP向ATP的转化，激活了肝脏中cAMP/CREB/SIRT3/AMPK/ACC通路。尼罗红染色表明，油酸处理的HepG2细胞中cAMP、SIRT3或AMPK的抑制抵消了咖啡因的作用。此外，敲低SIRT3可以下调咖啡因对AMPK和ACC的磷酸化。这些结果表明，咖啡因可能通过cAMP/CREB/SIRT3/AMPK/ACC通路促进脂质代谢，从而改善hed诱导的肝脏脂肪变性。SIRT3是连接咖啡因和脂质代谢的分子桥梁。
The beneficial effect of caffeine-containing food on non-alcoholic fatty liver disease (NAFLD) has been widely reported. The aim of this study was to explore the effect of caffeine on hepatic steatosis. C57BL/6 mice were randomly assigned to a normal diet or a high energy diet (HED). Caffeine was given to HED mice by oral gavage. Body weights, lipids in the liver and liver damage were measured. Meanwhile, cAMP, SIRT3 or AMPK inhibitors were treated respectively before incubation with caffeine in oleate-treated HepG2 cells. SIRT3 was further silenced by siRNA to confirm the results. Caffeine significantly decreased the mass of fat tissues, lipids, ALT and AST levels in the liver of HED-treated mice. Caffeine increased the transformation of ADP to ATP and activated the cAMP/CREB/SIRT3/AMPK/ACC pathway in the liver. Nile red staining demonstrated that suppression of cAMP, SIRT3 or AMPK in oleate-treated HepG2 cells counteracted the effect of caffeine. Moreover, knocking down SIRT3 could down-regulate AMPK and ACC phosphorylation by caffeine. These results demonstrate that caffeine could improve HED-induced hepatic steatosis by promoting lipid metabolism via the cAMP/CREB/SIRT3/AMPK/ACC pathway. SIRT3 functioned as a molecular bridge connecting caffeine and lipid metabolism.