Department of Animal Science, Shandong Agricultural University, Taian, Shandong 271018, China.
Division Animal and Human Health Engineering, Department of Biosystems, KU Leuven, Kasteelpark Arenberg 30, 3001 Leuven, Belgium.
Comp Biochem Physiol B Biochem Mol Biol. 2019 Jun;232:23-30. doi: 10.1016/j.cbpb.2019.02.001. Epub 2019 Feb 19.
Adenosine monophosphate-activated protein kinase (AMPK) plays a pivotal role in the regulation of carbohydrate, lipid, and protein metabolism in animals. In this study, we examined whether any cross talk exists between glucocorticoids and AMPK in the regulation of the liver bile acid biosynthesis pathway. Dexamethasone treatment decreased the growth performance of broiler chickens. The liver mRNA levels of fatty acid transport protein (FATP-1), farnesoid X receptor (FXR), AMPK alpha 1 subunit (AMPKα1), and glucocorticoid receptor were significantly upregulated in DEX-treated broilers; the gene expression of liver cholesterol 7 alpha-hydroxylase (CYP7A1) was significantly downregulated. The protein level of liver CYP7A1 was significantly decreased by DEX treatment at both 24 and 72 h, while the protein level of p-AMPK/ t-AMPK stayed unchanged. In the in vitro cultured hepatocytes, compound C pretreatment blocked the increase in CYP7A1 protein level by DEX and significantly suppressed FATP-1, SREBP-1c, FXR, and CYP7A1 gene expression stimulated by DEX. Compound C treatment significantly reduces the protein level of p-AMPK, and the combination of compound C and DEX significantly reduces the protein level of t-AMPK. Thus, glucocorticoids affected liver AMPK and the bile acid synthesis signal pathway, and AMPK might be involved in the glucocorticoid effect of liver bile acid synthesis.
一磷酸腺苷激活蛋白激酶（AMPK）在动物的碳水化合物、脂质和蛋白质代谢调节中起着关键作用。在这项研究中，我们研究了糖皮质激素和 AMPK 是否在调节肝脏胆汁酸生物合成途径方面存在相互作用。地塞米松处理降低了肉鸡的生长性能。DEX 处理的肉鸡肝脏脂肪酸转运蛋白（FATP-1）、法尼醇 X 受体（FXR）、AMPKα1 亚基（AMPKα1）和糖皮质激素受体的 mRNA 水平显著上调；肝脏胆固醇 7α-羟化酶（CYP7A1）的基因表达显著下调。DEX 处理 24 和 72 小时后，肝脏 CYP7A1 的蛋白水平显著降低，而 p-AMPK/t-AMPK 的蛋白水平保持不变。在体外培养的肝细胞中，化合物 C 预处理可阻断 DEX 引起的 CYP7A1 蛋白水平升高，并显著抑制 DEX 刺激的 FATP-1、SREBP-1c、FXR 和 CYP7A1 基因表达。化合物 C 处理显著降低 p-AMPK 的蛋白水平，而化合物 C 和 DEX 的组合可显著降低 t-AMPK 的蛋白水平。因此，糖皮质激素影响肝脏 AMPK 和胆汁酸合成信号通路，而 AMPK 可能参与肝脏胆汁酸合成的糖皮质激素效应。
