Animal Science, Department of Biological Production, Tokyo University of Agriculture and Technology, 3-5-8, Saiwai-cho, Fuchu-shi, Tokyo, 183-8509, Japan.
Comp Biochem Physiol A Mol Integr Physiol. 2011 Feb;158(2):201-6. doi: 10.1016/j.cbpa.2010.10.028. Epub 2010 Nov 3.
Liver X receptors (LXRs) are members of the nuclear receptor family of transcription factors. They play a crucial role in lipid metabolism processes such as bile acid and fatty acid synthesis, as well as minor or limited roles in the regulation of cholesterol synthesis and uptake in mammals. In avian species, however, little is known about the role of LXRs except for the fact that they are involved in the stimulation of fatty acid synthesis. In this study, we characterize the expression profile of genes related to bile acid, cholesterol, and fatty acid synthesis and VLDL secretion in chicken primary hepatocytes treated with T0901317, a synthetic agonist of LXR. The activity of chicken cholesterol 7α hydroxylase (CYP7A1), a key enzyme in bile acid synthesis, mRNA expression, and bile acid excretion, was stimulated by supplementation of the culture medium with a low concentration (0.01 μM) of T0901317. In contrast, the levels of sterol regulatory element binding protein (SREBP)-1, fatty acid synthase mRNA, and VLDL-triacylglycerol in cells cultured in the presence of a high concentration (10 μM) of T0901317 were higher than those cultured in zero or low concentrations of T0901317. These results suggest that cellular responses to this LXR agonist were similar to those present in mammals. A novel finding of this study concerned changes to the regulation of cholesterol synthesis and uptake in chicken hepatocytes treated with T0901317. Levels of SREBP-2,3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) and low-density lipoprotein receptor (LDLr) mRNA expression increased as a function of increasing T0901317 (up to 1.0 μM), but remained similar to those in cells cultured under control conditions when the concentration of T0901317 was increased to 10 μM. These results suggest that LXRs play an important role in cholesterol synthesis and uptake in chicken hepatocytes and, as such, differ to findings in mammals where the effect of LXR agonists on cholesterol synthesis plays only a minor role in the regulation of cellular sterol homeostasis.
肝 X 受体 (LXRs) 是核受体转录因子家族的成员。它们在脂质代谢过程中发挥着关键作用，如胆汁酸和脂肪酸的合成，以及在胆固醇合成和摄取的调节中发挥较小或有限的作用。然而，在禽类中，除了它们参与刺激脂肪酸合成之外，对于 LXR 的作用知之甚少。在这项研究中，我们描述了用 T0901317（LXR 的合成激动剂）处理鸡原代肝细胞后与胆汁酸、胆固醇和脂肪酸合成及 VLDL 分泌相关的基因表达谱。鸡胆固醇 7α羟化酶 (CYP7A1) 的活性、胆汁酸合成的关键酶、mRNA 表达和胆汁酸排泄，均受到培养基中低浓度（0.01 μM）T0901317 补充的刺激。相反，在高浓度（10 μM）T0901317 存在的情况下培养的细胞中，固醇调节元件结合蛋白 (SREBP)-1、脂肪酸合酶 mRNA 和 VLDL-三酰基甘油的水平高于在零或低浓度 T0901317 培养的细胞。这些结果表明，细胞对这种 LXR 激动剂的反应与哺乳动物中的反应相似。本研究的一个新发现涉及到 T0901317 处理的鸡肝细胞中胆固醇合成和摄取的调节变化。SREBP-2、3-羟基-3-甲基戊二酰基辅酶 A 还原酶 (HMGR) 和低密度脂蛋白受体 (LDLr) mRNA 表达水平随 T0901317 浓度的增加而增加（高达 1.0 μM），但当 T0901317 浓度增加到 10 μM 时，与对照条件下培养的细胞相似。这些结果表明，LXRs 在鸡肝细胞中胆固醇的合成和摄取中发挥重要作用，与哺乳动物不同，LXR 激动剂对胆固醇合成的影响在细胞甾醇稳态的调节中只起次要作用。
