Fads1 and 2 are promoted to meet instant need for long-chain polyunsaturated fatty acids in goose fatty liver
Fads1 and 2 are promoted to meet instant need for long-chain polyunsaturated fatty acids in goose fatty liver
复制标题
推广Fads1和2以满足鹅脂肪肝对长链多不饱和脂肪酸的即时需求
DOI：
10.1007/s11010-016-2737-7
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发表时间：
2016-07-01
影响因子：
4.3
通讯作者：
Geng, Tuoyu
中科院分区：
文献类型：
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作者：
Osman, Rashid H.;Liu, Long;Geng, Tuoyu
非酒精性脂肪性肝病（NAFLD）的全球流行对人类健康构成威胁。鹅是发现治疗靶点的NAFLD的独特模型，因为它的肝脏可以在没有明显损伤的情况下发生严重的脂肪变性。脂肪酸去饱和酶（Fads）是潜在的治疗靶点，因为Fads表达和突变与肝脏脂肪相关。在这里，我们假设Fads被促进为鹅脂肪肝提供保护。为了验证这一点，对鹅Fads 1和Fads 2进行了测序。采用定量PCR方法检测了Fads 1/2/6在鹅肝和原代肝细胞中的表达。肝脏脂肪酸组成也进行了分析，气相色谱法。结果表明，随着饲养时间的延长，肝脏Fads 1/2/6表达逐渐增加。相反，反式-C18：1 n9脂肪酸（Fads抑制剂）减少。然而，增强脂肪酸的能力，长链多不饱和脂肪酸（LC-PUFA）的合成是不足以弥补消耗的LC-PUFA在鹅脂肪肝。此外，细胞研究表明Fads 1/2/6的表达受脂肪肝相关因子的调节。总之，这些发现表明Fads 1/2作为保护性成分被促进以满足鹅脂肪肝中对LC-PUFAs的即时需求，并且我们提出这是没有肝损伤的严重肝脂肪变性所需的。
Global prevalence of non-alcoholic fatty liver disease (NAFLD) constitutes a threat to human health. Goose is a unique model of NAFLD for discovering therapeutic targets as its liver can develop severe steatosis without overt injury. Fatty acid desaturase (Fads) is a potential therapeutic target as Fads expression and mutations are associated with liver fat. Here, we hypothesized that Fads was promoted to provide a protection for goose fatty liver. To test this, goose Fads1 and Fads2 were sequenced. Fads1/2/6 expression was determined in goose liver and primary hepatocytes by quantitative PCR. Liver fatty acid composition was also analyzed by gas chromatography. Data indicated that hepatic Fads1/2/6 expression was gradually increased with the time of overfeeding. In contrast, trans-C18:1n9 fatty acid (Fads inhibitor) was reduced. However, enhanced Fads capacity for long-chain polyunsaturated fatty acid (LC-PUFA) synthesis was not sufficient to compensate for the depleted LC-PUFAs in goose fatty liver. Moreover, cell studies showed that Fads1/2/6 expression was regulated by fatty liver-associated factors. Together, these findings suggest Fads1/2 as protective components are promoted to meet instant need for LC-PUFAs in goose fatty liver, and we propose this is required for severe hepatic steatosis without liver injury.