Eicosapentaenoic acid attenuates hepatic accumulation of cholesterol esters but aggravates liver injury and inflammation in mice fed a cholate-supplemented high-fat diet

Eicosapentaenoic acid attenuates hepatic accumulation of cholesterol esters but aggravates liver injury and inflammation in mice fed a cholate-supplemented high-fat diet
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DOI:
10.2131/jts.38.379
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发表时间:
2013-06-01
影响因子:
2
通讯作者:
Tsuneyama, Koichi
Tsuneyama, Koichi
中科院分区:
医学4区
文献类型:
--
作者:
Watanabe, Shiro;Tsuneyama, Koichi

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在小鼠中给予胆酸钠补充的高脂肪(CAHF)饮食,可诱导肝脏中胆固醇酯(CE)的主要积累,以及肝损伤的生化和组织学特征。在饲喂CAHF饮食的小鼠肝脏中发现的CE中,油酸胆固醇含量最高。研究了二十碳五烯酸乙酯(EPA)对CAHF日粮小鼠肝脏CE积累和肝损伤的影响。补充EPA可抑制肝脏中油酸胆固醇水平的升高。CAHF组小鼠肝脏中甾醇o -酰基转移酶-2和硬脂酰辅酶a去饱和酶-1 mRNA的表达水平升高,但EPA组小鼠肝脏中甾醇o -酰基转移酶-2和硬脂酰辅酶a去饱和酶-1 mRNA的表达水平正常。然而,与CAHF组相比,epa组的血清转氨酶活性升高、炎症细胞渗出迹象和肝脏炎症基因反应均有所增强。我们证明,在饲喂CAHF日粮的小鼠中,补充EPA减轻了CE的积累,但加重了肝损伤和肝脏炎症。
The administration of a sodium cholate-supplemented high-fat (CAHF) diet in mice induced the predominant accumulation of cholesterol esters (CE) in the liver and biochemical and histological features of liver injury. Cholesteryl oleate was the most abundant CE found in the liver of the mice fed the CAHF diet. We examined the effect of ethyl eicosapentaenoate (EPA) on hepatic CE accumulation and liver injury in the mice fed the CAHF diet. The EPA supplementation suppressed the elevation in the level of cholesteryl oleate in the liver. The expression levels of sterol O-acyltransferase-2 and stearoyl-CoA desaturase-1 mRNA in the liver were elevated in the mice fed the CAHF diet, but they were normalized by the EPA supplementation. However, the elevation in serum transaminase activity, the sign of inflammatory cell exudation and inflammatory gene responses in the liver of the mice fed the EPA-supplemented diet were enhanced compared with those of the mice fed the CAHF diet. We demonstrated that EPA supplementation attenuated CE accumulation but aggravated liver injury and liver inflammation in the mice fed the CAHF diet.