研究简报 Short communications

糖皮质激素对鸡胚肝细胞脂肪和胆汁酸代谢相关基因表达的影响

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  • 山东农业大学动物科技学院/动物医学院, 泰安 271018
周华金(1993-),女,山东聊城人,硕士研究生,研究方向为动物营养与饲料科学。E-mail:1667569088@qq.com

收稿日期: 2018-04-05

  网络出版日期: 2018-10-20

基金资助

国家自然科学基金项目(31472115);山东省家禽产业创新团队项目(STAIT-011-08)

Effects of Glucocorticoids on Expression of Lipid and Bile Acid Metabolism Related Genes in Chicken Embryo Hepatocytes

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  • College of Animal Science and College of Veterinary Medicine, Shandong Agricultural University, Tai'an 271018, China

Received date: 2018-04-05

  Online published: 2018-10-20

摘要

为揭示应激导致家禽肝脏代谢异常的机理,本研究探查了糖皮质激素——地塞米松(DEX)对鸡胚肝细胞脂肪和胆汁酸代谢相关基因表达的影响。选取19胚龄的无特定病原体(SPF)鸡蛋,原代培养鸡胚肝细胞(37℃、5% CO2),用0(对照)、200、500、1 000 nmol/L的地塞米松分别处理24 h。结果表明:与对照组相比,高剂量(500、1 000 nmol/L)地塞米松处理显著降低了脂肪代谢相关基因——脂肪酸转运蛋白1(FATP-1)、固醇调节元件结合蛋白-1C(SREBP-1C)、载脂蛋白B100(APOB100)、肝脏X受体(LXR)以及胆汁酸摄取相关基因Na+/牛磺胆盐共转运体(NTCP)的mRNA相对表达水平(P<0.05),显著提高了胆汁酸排出相关基因——胆盐输出泵(BSEP)的mRNA相对表达水平(P<0.05);低剂量(200 nmol/L)地塞米松处理显著提高胆汁酸合成相关基因——胆固醇7-羟化酶(CYP7A1)和法尼酯X受体(FXR)的mRNA相对表达水平(P<0.05),同时,SREBP-1C的mRNA相对表达水平显著降低(P<0.05),BSEP的mRNA相对表达水平显著上升(P<0.05)。由此得出,高剂量糖皮质激素对鸡胚肝细胞的脂肪合成、转运和胆汁酸的摄取具有抑制作用;低剂量糖皮质激素可以促进胆汁酸的合成和排出,部分反应具有剂量依赖性。

本文引用格式

周华金, 杨家昶, 张辉, 王继光, 郝洋洋, 杜鹏, 宋志刚 . 糖皮质激素对鸡胚肝细胞脂肪和胆汁酸代谢相关基因表达的影响[J]. 动物营养学报, 2018 , 30(10) : 4262 -4268 . DOI: 10.3969/j.issn.1006-267x.2018.10.053

Abstract

In order to reveal the mechanism of stress-induced metabolism disorders of liver in poultry, this study explored the effect of glucocorticoid-dexamethasone (DEX) on the expression of fat and bile acid metabolism related genes in chicken embryo hepatocytes. Nineteen embryo age specific pathogen free (SPF) eggs were selected, and primary cultured (37℃, 5% CO2)chicken embryo hepatocytes were treated with 0 (control), 200, 500, and 1 000 nmol/L dexamethasone respectively for 24 h. The results showed as follows:compared with the control group, treated with the high dose (500 or 1 000 nmol/L) dexamethasone significantly reduced the mRNA relative expression levels of fat metabolism related genes, such as fatty acid transporter 1 (FATP-1), sterol regulatory element binding protein-1C (SREBP-1C), apolipoprotein B100 (APOB100) and liver X receptor (LXR) (P<0.05), and the mRNA relative expression level of bile acid uptake related gene Na+/taurocholate co-transporting polypeptide (NTCP) was also reduced (P<0.05); While the mRNA relative expression level of bile acid excretion related gene bile salt output pump (BSEP) was significantly increased (P<0.05); treated with the low dose (200 nmol/L) dexamethasone significantly increased the mRNA relative expression levels of bile acid synthesis related genes cholesterol7-alpha hydroxylase (CYP7A1) and farnesoid X receptor (FXR) (P<0.05), meanwhile, the SREBP-1C mRNA relative expression level was significantly decreased (P<0.05), and the BSEP mRNA relative expression level was significantly increased (P<0.05). In conclusion, high dose glucocorticoids can inhibit the synthesis and transport of fat and bile acid intake in chicken embryo hepatocytes, while low dose glucocorticoids can promote the synthesis and excretion of bile acids, some of these reactions have a dose-dependent response.

参考文献

[1] ROSE A J,HERZIG S.Metabolic control through glucocorticoid hormones:an update[J].Molecular and Cellular Endocrinology,2013,380(1/2):65-78.

[2] LIVINGSTONE D E,GRASSICK S L,CURRIE G L,et al.Dysregulation of glucocorticoid metabolism in murine obesity:comparable effects of leptin resistance and deficiency[J].Journal of Endocrinology,2009,201(2):211-218.  

[3] HARASIM-SYMBOR E,KONSTANYNOWICZ-NOWICKA K,CHABOWSKI A.Additive effects of dexamethasone and palmitate on hepatic lipid accumulation and secretion[J].Journal of Molecular Endocrinology,2016,57(4):261-273.  

[4] ROSE A J,DÍAZ M B,REIMANN A,et al.Molecular control of systemic bile acid homeostasis by the liver glucocorticoid receptor[J].Cell Metabolism,2011,14(1):123-130.  

[5] PRINCEN H M,MEIJER P,HOFSTEE B.Dexamethasone regulates bile acid synthesis in monolayer cultures of rat hepatocytes by induction of cholesterol 7α-hydroxylase[J].Biochemical Journal,1989,262(1):341-348.  

[6] LV Z P,PENG Y Z,ZHANG B,et al.Glucose and lipid metabolism disorders in the chickens with dexamethasone-induced oxidative stress[J].Journal of Animal Physiology and Animal Nutrition,2018,102(2):e706-e717.

[7] LIVAK K J,SCHMITTGEN T D.Analysis of relative gene expression data using real-time quantitative PCR and the 2-ΔΔCT method[J].Methods,2001,25(4):402-408.  

[8] WU T,YANG L,JIANG J G,et al.Chronic glucocorticoid treatment induced circadian clock disorder leads to lipid metabolism and gut microbiota alterations in rats[J].Life Sciences,2018,192:173-182.

[9] QI R L,FENG M,TAN X,et al.FATP1 silence inhibits the differentiation and induces the apoptosis in chicken preadipocytes[J].Molecular Biology Reports,2013,40(4):2907-2914.  

[10] MARTIN G,POIRIER H,HENNUYER N,et al.Induction of the fatty acid transport protein 1 and acyl-CoA synthase genes by dimer-selective rexinoids suggests that the peroxisome proliferator-activated receptor-retinoid X receptor heterodimer is their molecular target[J].Journal of Biological Chemistry,2000,275(17):12612-12618.  

[11] 韩春春,黄晓宇,王继文.鹅LXRα基因的克隆及填饲对其mRNA水平的影响[J].畜牧兽医学报,2009,40(9):1405-1409.

[12] AOKI N,YOSHIDA D,ISHIKAWA R,et al.A single daily meal at the beginning of the active or inactive period inhibits food deprivation-induced fatty liver in mice[J].Nutrition Research,2014,34(7):613-622.  

[13] 张晾,张燕燕,叶玲敏,等.多不饱和脂肪酸饮食对载脂蛋白E缺失小鼠含载脂蛋白B100脂蛋白代谢的影响[J].生物化学与生物物理进展,2015,42(9):843-849.

[14] 张森,石慧,李辉.鸡apoB基因T123G多态位点与生长和体组成性状的相关性研究[J].畜牧兽医学报,2006,37(12):1264-1268.

[15] 高广亮,张庆秋,李辉,等.鸡肝细胞中L-BABP基因表达对脂类代谢基因及甘油三酯和总胆固醇的影响[J].畜牧兽医学报,2015,46(1):32-40.

[16] LI T G,CHIANG J Y L.Bile acid signaling in metabolic disease and drug therapy[J].Pharmacological Reviews,2014,66(4):948-983.  

[17] WARSKULAT U,KUBITZ R,WETTSTEIN M,et al.Regulation of bile salt export pump mRNA levels by dexamethasone and osmolarity in cultured rat hepatocytes[J].Biological Chemistry,1999,380(11):1273-1279.

[18] ELLIS E,GOODWIN B,ABRAHAMSSON A,et al.Bile acid synthesis in primary cultures of rat and human hepatocytes[J].Hepatology,1998,27(2):615-620.  

[19] WANG L,LEE Y K,BUNDMAN D,et al.Redundant pathways for negative feedback regulation of bile acid production[J].Developmental Cell,2002,2(6):721-731.  

[20] KERR T A,SAEKI S,SCHNEIDER M,et al.Loss of nuclear receptor SHP impairs but does not eliminate negative feedback regulation of bile acid synthesis[J].Developmental Cell,2002,2(6):713-720.  

[21] ZOLLNER G,WAGNER M,FICKERT P,et al.Role of nuclear receptors and hepatocyte-enriched transcription factors for Ntcp repression in biliary obstruction in mouse liver[J].American Journal of Physiology-Gastrointestinal and Liver Physiology,2005,289(5):G798-G805.

[22] PLASS J R M,MOL O,HEEGSMA J,et al.Farnesoid X receptor and bile salts are involved in transcriptional regulation of the gene encoding the human bile salt export pump[J].Hepatology,2002,35(3):589-596.  
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