Differential gene expression pattern in hypothalamus of chickens during fasting-induced metabolic reprogramming: Functions of glucose and lipid metabolism in the feed intake of chickens
Differential gene expression pattern in hypothalamus of chickens during fasting-induced metabolic reprogramming: Functions of glucose and lipid metabolism in the feed intake of chickens
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禁食诱导的代谢重编程过程中鸡下丘脑的差异基因表达模式：葡萄糖和脂质代谢在鸡采食中的功能
DOI：
10.3382/ps.2014-04047
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发表时间：
2014-11-01
期刊：
影响因子：
4.4
通讯作者：
Shu, Gang
中科院分区：
文献类型：
--
作者：
Fang, Xin-Ling;Zhu, Xiao-Tong;Shu, Gang
禁食诱导的下丘脑代谢重编程参与调节哺乳动物的能量稳态和食欲，但这一现象在家禽中仍不清楚。在这项研究中，一组基因的表达模式相关的神经肽，葡萄糖和脂质代谢酶在鸡的下丘脑禁食和再喂养的特点是通过微阵列分析和定量PCR。结果显示，禁食48 h可上调（P < 0.05）促食欲神经肽Y和刺豚鼠相关蛋白的mRNA表达，但下调（P < 0.05）促食欲神经肽原阿黑皮素、生长激素释放激素、胰岛淀粉样多肽、促甲状腺激素β和糖蛋白激素α多肽的mRNA表达。禁食48小时后，脂肪酸β-氧化[过氧化物酶体增殖物激活受体α]的mRNA表达（PPAR α）、肉毒碱棕榈酰转移酶1A和叉头盒O 1]、能量传感器蛋白[沉默调节蛋白1（SIRT 1）和叉头盒O 1]和糖酵解抑制剂（丙酮酸脱氢酶激酶，同工酶4）的表达增强，而脂肪酸合成和转运相关基因的表达增强（乙酰辅酶A羧化酶α、脂肪酸合成酶、载脂蛋白A-I、内皮脂肪酶和脂肪酸结合蛋白7）被抑制。肝脏和肌肉也表现出与下丘脑相似的葡萄糖和脂质代谢相关基因的表达模式，除了乙酰辅酶A羧化酶α，酰基辅酶A合成酶长链家族成员4和载脂蛋白A-I。侧脑室（ICV）注射实验的结果证实，α-硫辛酸（ALA，丙酮酸脱氢酶激酶，同工酶4抑制剂，0.10 μ mol）和NADH（SIRT 1抑制剂，0.80 μ mol）显著抑制鸡的食欲，而2-脱氧-D-葡萄糖（糖酵解抑制剂，0.12 - 1.20 μ mol）和NAD（+）（SIRT 1激活剂，0.08 - 0.80 μ mol）增加鸡的采食量。NAD（+）的促食欲作用也可被NADH阻断。然而，ICV注射GW 7647（PPAR α激动剂）或GW 6471（PPAR α拮抗剂）对摄食量没有影响。结果表明，下丘脑糖酵解（ALA抑制，2-脱氧-D-葡萄糖促进）和SIRT 1（NADH抑制，NAD（+）促进）可能参与鸡采食量的调节，而非PPAR α。
Fasting-induced hypothalamic metabolic reprogramming is involved in regulating energy homeostasis and appetite in mammals, but this phenomenon remains unclear in poultry. In this study, the expression patterns of a panel of genes related to neuropeptides, glucose, and lipid metabolism enzymes in the hypothalamus of chickens during fasting and refeeding were characterized by microarray analysis and quantitative PCR. Results showed that 48 h of fasting upregulated (P < 0.05) the mRNA expressions of orexigenic neuropeptide Y and agouti-related protein but downregulated (P < 0.05) that of anorexigenic neuropeptide pro-opiomelanocortin; growth hormone-releasing hormone; islet amyloid polypeptide; thyroid-stimulating hormone, beta; and glycoprotein hormones, alpha polypeptide. After 48 h of fasting, the mRNA expression of fatty acid beta-oxidation [peroxisome proliferator-activated receptor alpha (PPAR alpha), carnitine palmitoyltransferase 1A, and forkhead box O1], energy sensor protein [sirtuin 1 (SIRT1) and forkhead box O1], and glycolysis inhibitor (pyruvate dehydrogenase kinase, isozyme 4) were enhanced, but that of fatty acid synthesis and transport associated genes (acetyl-CoA carboxylase alpha, fatty acid synthase, apolipoprotein A-I, endothelial lipase, and fatty acid binding protein 7) were suppressed. Liver and muscle also demonstrated similar expression patterns of genes related to glucose and lipid metabolism with hypothalamus, except for that of acetyl-CoA carboxylase alpha, acyl-CoA synthetase long-chain family member 4, and apolipoprotein A-I. The results of intracerebro-ventricular (ICV) injection experiments confirmed that alpha-lipoic acid (ALA, pyruvate dehydrogenase kinase, isozyme 4 inhibitor, 0.10 mu mol) and NADH (SIRT1 inhibitor, 0.80 mu mol) significantly suppressed the appetite of chickens, whereas 2-deoxy-D-glucose (glycolytic inhibitor, 0.12 to 1.20 mu mol) and NAD(+) (SIRT1 activator, 0.08 to 0.80 mu mol) increased feed intake in chickens. The orexigenic effect of NAD(+) was also blocked by cotreatment with NADH. However, ICV injection of either GW7647 (PPAR alpha agonist) or GW6471 (PPAR alpha antagonist) showed no effects on feed intake. Results suggested that hypothalamic glycolysis (inhibited by ALA and promoted by 2-deoxy-D-glucose) and SIRT1 (inhibited by NADH and promoted by NAD(+)), not PPAR alpha, were probably involved in feed intake regulation in chickens.