High-fat and high-sucrose (western) diet induces steatohepatitis that is dependent on fructokinase.
High-fat and high-sucrose (western) diet induces steatohepatitis that is dependent on fructokinase.
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DOI：
10.1002/hep.26594
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发表时间：
2013-11
期刊：
影响因子：
13.5
通讯作者：
Johnson, Richard J.
中科院分区：
文献类型：
--
作者：
Ishimoto, Takuji;Lanaspa, Miguel A.;Rivard, Christopher J.;Roncal-Jimenez, Carlos A.;Orlicky, David J.;Cicerchi, Christina;McMahan, Rachel H.;Abdelmalek, Manal F.;Rosen, Hugo R.;Jackman, Matthew R.;MacLean, Paul S.;Diggle, Christine P.;Asipu, Aruna;Inaba, Shinichiro;Kosugi, Tomoki;Sato, Waichi;Maruyama, Shoichi;Sanchez-Lozada, Laura G.;Sautin, Yuri Y.;Hill, James O.;Bonthron, David T.;Johnson, Richard J.
从添加糖中摄入果糖被认为是非酒精性脂肪肝的一个原因。在这里，我们测试了果糖可能与高脂饮食相互作用以诱导脂肪肝的假设，并确定这是否依赖于果糖代谢中的关键酶，果糖激酶。将野生型或果糖激酶敲除小鼠喂食低脂肪（11%）、高脂肪（36%）或高脂肪（36%）和高蔗糖（30%）饮食15周。野生型和果糖激酶基因敲除小鼠均发生肥胖，伴有轻度肝脂肪变性，与低脂饮食相比，高脂饮食没有肝脏炎症的证据。相比之下，喂食高脂肪和高蔗糖饮食的野生型小鼠发生更严重的肝脂肪变性，伴有低度炎症和纤维化，如通过增加的CD 68、TNF-α、MCP-1、α-平滑肌肌动蛋白和胶原蛋白I和TIMP 1表达所指出的。这些变化在果糖激酶敲除小鼠中被阻止。高脂高糖饮食对肝脂肪变性的发生存在累加效应。此外，蔗糖与高脂肪饮食的组合可诱导脂肪性肝炎。果糖激酶敲除小鼠的保护作用表明果糖（来自蔗糖）在脂肪性肝炎的发展中起关键作用。这些研究强调了果糖在脂肪肝和非酒精性脂肪性肝炎（NASH）发展中的重要作用。
Fructose intake from added sugars has been implicated as a cause of nonalcoholic fatty liver disease. Here we tested the hypothesis that fructose may interact with high fat diet to induce fatty liver, and to determine if this was dependent on a key enzyme in fructose metabolism, fructokinase. Wild type or fructokinase knockout mice were fed a low fat (11%), high fat (36%) or high fat (36%) and high sucrose (30%) diet for 15 weeks. Both wild type and fructokinase knockout mice developed obesity with mild hepatic steatosis and no evidence for hepatic inflammation on a high fat diet compared to a low fat diet. In contrast, wild type mice fed a high fat and high sucrose diet developed more severe hepatic steatosis with low grade inflammation and fibrosis, as noted by increased CD68, TNF-alpha, MCP-1, alpha-smooth muscle actin, and collagen I and TIMP1 expression. These changes were prevented in the fructokinase knockout mice. An additive effect of high fat and high sucrose diet on the development of hepatic steatosis exists. Further, the combination of sucrose with high fat diet may induce steatohepatitis. The protection in fructokinase knockout mice suggests a key role for fructose (from sucrose) in this development of steatohepatitis. These studies emphasize the important role of fructose in the development of fatty liver and nonalcoholic steatohepatitis (NASH).
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影响因子：
9.8
作者：
Roncal-Jimenez, Carlos A.;Lanaspa, Miguel A.;Rivard, Christopher J.;Nakagawa, Takahiko;Gabriela Sanchez-Lozada, L.;Jalal, Diana;Andres-Hernando, Ana;Tanabe, Katsuyuki;Madero, Magdalena;Li, Nanxing;Cicerchi, Christina;Mc Fann, Kim;Sautin, Yuri Y.;Johnson, Richard J.
通讯作者：
Johnson, Richard J.
影响因子：
24.5
作者：
Kechagias S;Ernersson A;Dahlqvist O;Lundberg P;Lindström T;Nystrom FH;Fast Food Study Group
通讯作者：
Fast Food Study Group
影响因子：
13.5
作者：
Abdelmalek, Manal F.;Lazo, Mariana;Horska, Alena;Bonekamp, Susanne;Lipkin, Edward W.;Balasubramanyam, Ashok;Bantle, John P.;Johnson, Richard J.;Diehl, Anna Mae;Clark, Jeanne M.
通讯作者：
Clark, Jeanne M.
影响因子：
6.9
作者：
Ventura, Emily E.;Davis, Jaimie N.;Goran, Michael I.
通讯作者：
Goran, Michael I.
影响因子：
4.4
作者：
Toshimitsu, Kumiko;Matsuura, Bunzo;Onji, Morikazu
通讯作者：
Onji, Morikazu