Berberine Ameliorates Hepatic Steatosis and Suppresses Liver and Adipose Tissue Inflammation in Mice with Diet-induced Obesity.
Berberine Ameliorates Hepatic Steatosis and Suppresses Liver and Adipose Tissue Inflammation in Mice with Diet-induced Obesity.
复制标题
DOI：
10.1038/srep22612
复制
发表时间：
2016-03-03
影响因子：
4.6
通讯作者：
Wu C
中科院分区：
文献类型：
--
作者：
Guo T;Woo SL;Guo X;Li H;Zheng J;Botchlett R;Liu M;Pei Y;Xu H;Cai Y;Zeng T;Chen L;Li X;Li Q;Xiao X;Huo Y;Wu C
越来越多的证据表明，小檗碱（BBR）对肥胖相关的非酒精性脂肪性肝病（NAFLD）有益。然而，BBR如何改善NAFLD的各个方面仍有待阐明。在此，我们揭示了BBR抑制肥胖相关炎症和改善肝脂肪变性的AMP活化蛋白激酶（AMPK）非依赖性机制。在喂食高脂饮食（HFD）的C57 BL/6 J小鼠中，BBR治疗可降低肝脏和脂肪组织中的炎症，如JNK 1磷酸化状态和促炎细胞因子mRNA水平的降低所示。BBR治疗还减少了肝脂肪变性，以及乙酰辅酶A羧化酶和脂肪酸合成酶的表达。有趣的是，用BBR处理没有显著改变HFD喂养小鼠的肝脏和脂肪组织中AMPK的磷酸化状态。结论：BBR处理可显著降低肝癌H4 IIE细胞和小鼠原代肝细胞中JNK 1的磷酸化水平，且呈剂量依赖性和时间依赖性，与AMPK磷酸化无关。BBR处理还导致原代小鼠肝细胞中棕榈酸酯诱导的脂肪沉积减少。总之，这些结果表明，BBR对改善NAFLD方面的作用在很大程度上归因于BBR对炎症的抑制，这与AMPK无关。
Increasing evidence demonstrates that berberine (BBR) is beneficial for obesity-associated non-alcoholic fatty liver disease (NAFLD). However, it remains to be elucidated how BBR improves aspects of NAFLD. Here we revealed an AMP-activated protein kinase (AMPK)-independent mechanism for BBR to suppress obesity-associated inflammation and improve hepatic steatosis. In C57BL/6J mice fed a high-fat diet (HFD), treatment with BBR decreased inflammation in both the liver and adipose tissue as indicated by reduction of the phosphorylation state of JNK1 and the mRNA levels of proinflammatory cytokines. BBR treatment also decreased hepatic steatosis, as well as the expression of acetyl-CoA carboxylase and fatty acid synthase. Interestingly, treatment with BBR did not significantly alter the phosphorylation state of AMPK in both the liver and adipose tissue of HFD-fed mice. Consistently, BBR treatment significantly decreased the phosphorylation state of JNK1 in both hepatoma H4IIE cells and mouse primary hepatocytes in both dose-dependent and time-dependent manners, which was independent of AMPK phosphorylation. BBR treatment also caused a decrease in palmitate-induced fat deposition in primary mouse hepatocytes. Taken together, these results suggest that BBR actions on improving aspects of NAFLD are largely attributable to BBR suppression of inflammation, which is independent of AMPK.