In dairy cows, fatty liver is one of the most common metabolic diseases that occurs during the periparturient period. Angiopoietin‐like protein 4 (ANGPTL4) is a well‐known downstream target of peroxisome proliferator‐activated receptors (PPARs), which regulate the glucose and fatty acid metabolisms. The inhibition of lipoprotein lipase (LPL) activity interferes with the storage of triglycerides (TG) in adipocytes, which plays an essential role in lipid metabolism in rodents. However, it remains unclear whether ANGPTL4 is involved in the pathological process of fatty liver in dairy cows as a result of the regulation of the hepatocellular lipid transport system. This study intended to investigate the effect of ANGPTL4 on the very‐low‐density lipoprotein (VLDL) assembly and secretion in bovine hepatocytes. Bovine hepatocytes were isolated using a modified two‐step perfusion and collagenase digestion process, and treated with different concentrations of ANGPTL4 (0, 4, 12, and 24 ng/ml) for 24 hr. The results showed that a high concentration of ANGPTL4 could significantly increase the extracellular concentration of VLDL while reducing the intracellular content of TG. Thus, it was confirmed that ANGPTL4 could promote the transport of TG in the form of VLDL by partially regulating the expression of related proteins in hepatocytes, thereby contributing to the partial adaptive regulation of lipid transport in dairy cows.

中文翻译：

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血管生成素样蛋白4在体外促进牛肝细胞极低密度脂蛋白的组装和分泌

在奶牛中，脂肪肝是围产期最常见的代谢疾病之一。血管生成素样蛋白 4 (ANGPTL4) 是众所周知的过氧化物酶体增殖物激活受体 (PPAR) 的下游靶标，其调节葡萄糖和脂肪酸代谢。脂蛋白脂肪酶 (LPL) 活性的抑制会干扰脂肪细胞中甘油三酯 (TG) 的储存，后者在啮齿动物的脂质代谢中起重要作用。然而，ANGPTL4是否由于肝细胞脂质转运系统的调节而参与奶牛脂肪肝的病理过程尚不清楚。本研究旨在研究 ANGPTL4 对牛肝细胞极低密度脂蛋白 (VLDL) 组装和分泌的影响。使用改良的两步灌注和胶原酶消化过程分离牛肝细胞，并用不同浓度的 ANGPTL4（0、4、12 和 24 ng/ml）处理 24 小时。结果表明，高浓度的ANGPTL4可以显着增加VLDL的细胞外浓度，同时降低细胞内TG的含量。由此证实ANGPTL4可以通过部分调节肝细胞相关蛋白的表达促进TG以VLDL的形式转运，从而有助于奶牛脂质转运的部分适应性调节。结果表明，高浓度的ANGPTL4可以显着增加VLDL的细胞外浓度，同时降低细胞内TG的含量。由此证实ANGPTL4可以通过部分调节肝细胞相关蛋白的表达促进TG以VLDL的形式转运，从而有助于奶牛脂质转运的部分适应性调节。结果表明，高浓度的ANGPTL4可以显着增加VLDL的细胞外浓度，同时降低细胞内TG的含量。由此证实ANGPTL4可以通过部分调节肝细胞相关蛋白的表达促进TG以VLDL的形式转运，从而有助于奶牛脂质转运的部分适应性调节。