Alleviation of high-fat diet-induced fatty liver damage in group IVA phospholipase A2-knockout mice.
Alleviation of high-fat diet-induced fatty liver damage in group IVA phospholipase A2-knockout mice.
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DOI：
10.1371/journal.pone.0008089
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发表时间：
2009-12-01
期刊：
影响因子：
3.7
通讯作者：
Akiba S
中科院分区：
文献类型：
--
作者：
Ii H;Yokoyama N;Yoshida S;Tsutsumi K;Hatakeyama S;Sato T;Ishihara K;Akiba S
肝脂肪沉积伴肝细胞损害是非酒精性脂肪性肝病的一个特征，它是由包括前列腺素在内的几个假定因素介导的。在本研究中，我们利用IVA-PLA2基因敲除小鼠，研究了催化前列腺素生物合成第一步的IVA磷脂酶A2(IVA-PLA2)是否与脂肪肝的发生有关。与正常饮食的野生型小鼠相比，高脂饮食(20%脂肪和1.25%胆固醇)的雄性野生型小鼠出现了肝细胞空泡化和肝脏肥大，血清中肝损伤标志物转氨酶的水平增加。这些高脂饮食诱导的改变在IVA-PLA2基因敲除小鼠中显著减少。在正常饮食条件下，IVA-PLA2基因敲除小鼠的肝脏三酰甘油含量低于野生型小鼠。尽管高脂饮食增加了两种基因型的肝脏三酰甘油含量，但IVA-PLA2基因敲除小鼠的程度低于野生型小鼠。在高脂饮食条件下，IVA-PLA2基因敲除小鼠的附睾脂肪垫重量低于野生型小鼠，脂肪细胞体积较小。无论饮食种类如何，IVA-PLA2基因敲除小鼠的血清前列腺素E_2水平均低于野生型小鼠。在两种基因型中，高脂饮食使两组的血清瘦素水平平均升高，但不影响血清脂联素、抵抗素、游离脂肪酸、三酰甘油、葡萄糖或胰岛素的水平。我们的发现表明，IVA-PLA2缺乏可以减轻高脂饮食引起的脂肪肝损伤，这可能是因为IVA-PLA2代谢物的生成较少，如前列腺素E2。IVA-PLA2有望成为包括非酒精性脂肪性肝病在内的肥胖相关疾病的治疗靶点。
Hepatic fat deposition with hepatocellular damage, a feature of non-alcoholic fatty liver disease, is mediated by several putative factors including prostaglandins. In the present study, we examined whether group IVA phospholipase A2 (IVA-PLA2), which catalyzes the first step in prostanoid biosynthesis, is involved in the development of fatty liver, using IVA-PLA2-knockout mice. Male wild-type mice on high-fat diets (20% fat and 1.25% cholesterol) developed hepatocellular vacuolation and liver hypertrophy with an increase in the serum levels of liver damage marker aminotransferases when compared with wild-type mice fed normal diets. These high-fat diet-induced alterations were markedly decreased in IVA-PLA2-knockout mice. Hepatic triacylglycerol content was lower in IVA-PLA2-knockout mice than in wild-type mice under normal dietary conditions. Although high-fat diets increased hepatic triacylglycerol content in both genotypes, the degree was lower in IVA-PLA2-knockout mice than in wild-type mice. Under the high-fat dietary conditions, IVA-PLA2-knockout mice had lower epididymal fat pad weight and smaller adipocytes than wild-type mice. The serum level of prostaglandin E2, which has a fat storage effect, was lower in IVA-PLA2-knockout mice than in wild-type mice, irrespective of the kind of diet. In both genotypes, high-fat diets increased serum leptin levels equally between the two groups, but did not affect the serum levels of adiponectin, resistin, free fatty acid, triacylglycerol, glucose, or insulin. Our findings suggest that a deficiency of IVA-PLA2 alleviates fatty liver damage caused by high-fat diets, probably because of the lower generation of IVA-PLA2 metabolites, such as prostaglandin E2. IVA-PLA2 could be a promising therapeutic target for obesity-related diseases including non-alcoholic fatty liver disease.
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影响因子：
2.4
作者：
Akagiri, Satomi;Naito, Yuji;Ichikawa, Hiroshi;Mizushima, Katsura;Takagi, Tomohisa;Handa, Osamu;Kokura, Satoshi;Yoshikawa, Toshikazu
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作者：
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LEHMANN, JM
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13.5
作者：
Hui, JM;Hodge, A;George, J
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George, J
影响因子：
56.9
作者：
Banerjee, RR;Rangwala, SM;Lazar, MA
通讯作者：
Lazar, MA
影响因子：
3.5
作者：
Mazid, Md. Abdul;Asad Chowdhury, Abu;Yokota, Kazushige
通讯作者：
Yokota, Kazushige