Isocaloric Pair-Fed High-Carbohydrate Diet Induced More Hepatic Steatosis and Inflammation than High-Fat Diet Mediated by miR-34a/SIRT1 Axis in Mice.
Isocaloric Pair-Fed High-Carbohydrate Diet Induced More Hepatic Steatosis and Inflammation than High-Fat Diet Mediated by miR-34a/SIRT1 Axis in Mice.
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DOI：
10.1038/srep16774
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发表时间：
2015-11-26
影响因子：
4.6
通讯作者：
Wang XD
中科院分区：
文献类型：
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作者：
Li X;Lian F;Liu C;Hu KQ;Wang XD
为探讨等热量高脂饮食和高碳水化合物饮食对小鼠肝脏脂肪变性的影响及其机制，特别是MicroRNA-34a/Silent信息调节因子T1轴的作用，将C57BL/6J小鼠(n = 12只/组)等热量配对喂饲含高脂肪和高碳水化合物的Lieber-DeCarli液体饲料16周。与饲喂高脂饲料的小鼠相比，尽管最终体重相似，但高脂饮食组小鼠：(1)引起更严重的肝脏脂肪变性；(2)肝脏miR-34a的表达上调，同时sirt1和烟酰胺磷酸核糖转移酶、sirt1活性和AMPK的磷酸化水平显著降低；(3)新生脂肪生成相关蛋白(Acc、Scd1)的表达上调，miR122、miR370和miR33的表达下调；(4)与脂肪酸氧化相关的基因Cpt1、PPARα和PGC1mRNA的表达降低；(5)增加肝脏总胆固醇浓度，降低胆固醇代谢相关基因Abcg5、Abcg8、Abcg11、Cyp7a1和Cyp8b1的表达；(6)诱导肝脏炎症反应增强，同时IL1β、肿瘤坏死因子α和Mcp1mRNA表达显著增加。因此，等热量的HCLD饲喂比HFLD饲喂诱导了更严重的肝脏脂肪变性和炎症反应，可能是通过miR-34a/SIRT1轴介导的促进DNL，抑制脂肪酸氧化和胆固醇代谢。
To investigate the different effects of isocaloric high-fat diet (HFD) and high-carbohydrate diet (HCD) on hepatic steatosis and the underlying mechanisms, especially the role of microRNA-34a/silent information regulator T1 (SIRT1) axis, C57BL/6J mice (n = 12/group) were isocaloric pair-fed with Lieber-DeCarli liquid diet containing either high fat (HFLD) or high carbohydrate (HCLD) for 16 weeks. As compared to the HFLD fed mice, despite the similar final body weights, HCLD feeding: (1) induced more severe hepatic steatosis; (2) up-regulated hepatic expression of miR-34a accompanied with significant decrease of SIRT1 and nicotinamide phosphoribosyltransferase (NAMPT), SIRT1 activity and phosphorylation of AMPK; (3) up-regulated de novo lipogenesis (DNL) related proteins expression (ACC, SCD1), and down-regulated expressions of miR-122, miR-370 and miR-33; (4) decreased mRNA expressions of genes Cpt1, Pparα and Pgc1α related to fatty acid oxidation; (5) increased hepatic total cholesterol concentration and decreased expression of cholesterol metabolism related genes Abcg5, Abcg8, Abcg11, Cyp7a1 and Cyp8b1; and (6) induced higher hepatic inflammatory response accompanied with significant increased mRNA expressions of Il1β, Tnfα and Mcp1. Thus, isocaloric HCLD feeding induced greater severity in hepatic steatosis and inflammatory response than HFLD feeding, potentially through miR-34a/SIRT1 axis mediated promotion of DNL, inhibition of fatty acid oxidation and cholesterol metabolism.