摘要
为对糖皮质激素调控肉仔鸡能量食欲的mTOR通路进行探索,本研究利用人工导入外源糖皮质激素的方法模拟应激,从应激发展的两个阶段——急性和长期过程着手,分别分析了下丘脑mTOR通路相关基因和食欲相关基因表达量的改变,并分析了下丘脑中mTOR通路相关蛋白的磷酸化程度,为应激状态下下丘脑能量食欲调控模式的建立和改善实际生产中应激引起的能量浪费提供理论依据。
第一部分,我们主要对长期注射DEX所引发的应激进行研究,共分两个试验。试验一0日龄AA (Arbor Acres)雄性肉仔鸡120只,正常饲喂至4日龄。4日龄起,试验动物在每天的2:00-3:00, 8:00-9:00,14:00-15:00,20:00-21:00进行饲喂,直至试验结束。Trial 1选取体重相近的11日龄AA雄性肉仔鸡40只,平均分为A、B两个组。每组设10个重复,每个重复2只鸡。11日龄起早6:00,A组按2.6 mg/kg BW的剂量皮下注射地塞米松磷酸钠,B组同剂量皮下注射生理盐水,连续注射三天。13日龄8:00和9:00两个时间点分别从每个重复取1只鸡,静脉采血后,颈部移位屠宰,迅速剥离下丘脑液氮保存,待RNA提取。血液样品3000rpm离心10min后取血浆,冷冻保存待测。Trial 2分组同trial 1,11日龄起注射时间为每天10:00(空腹1h), 13日龄的12:00(处理2h,空腹3h)采样,样品采集同trial 1。试验主要结果显示:糖皮质激素在采食前即8:00(处理2h,空腹5h)对mTOR通路各个因子的mRNA相对表达量均未出现显著影响;恢复饲喂1h后(9:00),糖皮质激素显著上调了PI3Cα的mRNA相对表达量,且糖皮质激素组PI3Cβ,EEF2也有上调的趋势。对其它因子的影响差异并不显著。Trial 2的结果表明糖皮质激素在12:00(处理2h,空腹3h)对肉仔鸡下丘脑中各个因子mRNA的相对表达量的影响均不显著。
试验二将AA雄性肉仔鸡正常饲喂至4日龄,4日龄后按试验一的方式用正常日粮对试验动物进行分段饲喂。将体重相近的9日龄AA雄性肉仔鸡48只,平均分为A、B、C、D四个组。9日龄起A、B两组分段饲喂高能日粮(代谢能,3.6kcal/kg;粗蛋白,20%),C、D两组分段饲喂低能日粮(代谢能,2.6kcal/kg;粗蛋白,20%),试验在单饲笼内进行,每组设6个重复,每个重复2只鸡。11日龄起每天6:00,A、C组按2.6 mg/kg BW的剂量皮下注射地塞米松磷酸钠,B、D两组皮下注射同剂量的生理盐水,连续注射三天。13日龄早8:00(取样后A、B饲喂高能日粮,C、D两组饲喂等量低能日粮)和9:00两个时间点分别从每个重复取1只鸡,静脉采血后,颈部移位屠宰,迅速剥离下丘脑,待RNA提取。血液样品3000rpm离心10min后取血浆,冷冻保存待测。试验结果表明:低能日粮采食条件下糖皮质激素对肉仔鸡采食前、后下丘脑中NPY, GR, INSR, AKT3, 4EBP1, mTOR, AgRP, POMC的mRNA相对表达量影响均不明显。糖皮质激素处理使低能日粮组试验动物采食后GR mRNA相对表达量有下调趋势,AgRP mRNA相对表达量有上调的趋势。高能日粮采食条件下,糖皮质激素注射组显著的上调了采食前肉仔鸡下丘脑中INSR, AKT3, 4EBP1的mRNA相对表达量(P<0.05),而POMC mRNA相对表达量有下调的趋势,上述变化在采食后均消失。糖皮质激素对高能日粮采食前、后丘脑中NPY, GR, mTOR, AgRP mRNA相对表达量的影响差异均不显著(P>0.05)。
第二部分,将体重相近的10日龄AA雄性肉仔鸡96只随机分为六组,每组8个重复。10日龄早9:00对所有试验肉仔鸡禁食处理,11日龄早6:00按A、B、C(处理组),A’、B’、C’(对照组)进行处理,11日龄9:00,将A,A’两组处死取样,同时B、B’两组饲喂高能日粮,C、C’两组饲喂低能日粮,10:00对剩余试验肉仔鸡取样。试验结果显示:糖皮质激素单次注射对空腹状态下肉仔鸡下丘脑中AgRP,NPY, POMC, GR,Ghrelin,MC4R,INSR的mRNA相对表达量均没有显著影响(P>0.05)。恢复饲喂1h高能日粮后,糖皮质激素显著上调了下丘脑中NPY mRNA的相对表达量(P<0.01),但糖皮质激素在上述条件下对肉仔鸡下丘脑中AgRP, POMC, GR, Ghrelin, MC4R, INSR的mRNA相对表达量影响均不显著(P>0.05);恢复饲喂低能日粮后,糖皮质激素使肉仔鸡下丘脑中NPY mRNA的相对表达量有上调趋势,但该条件下AgRP, POMC, GR, Ghrelin, MC4R, INSR的影响均不显著(P>0.05)。
To investigate the effects and mechanisms of glucocorticoids on the mammalian target of rapamycin (mTOR) appetite and energy pathway of broilers (Gallus gallus domesticus), exogenous glucocorticoids was used to mimick stress on two phases of stress development of broilers. Changes of Protein and mRNA expression level of important genes in appetite regulation and mTOR pathway in hypothalamus were measured and analyzed, in order to providing countermeasures for reforming energy waste in broiler chicken production. In experiment 1, there were two similar trails. In trial 1, 80 male AA broilers were divided into two groups: glucocorticoids and control. Each group had 10 repetitions and each repetition had 4 broilers. Broilers were injected with the same dose of dexamethasone(DEX) and saline at 6:00 (11d-13d), respectively. At the day of 13, samples (blood and hypothalamus) were obtained at 8:00 and 9:00. In trial 2, group dividing and the treatment were the same as which in trail 1, except that the time of injection was 10:00, and samples were obtained at 12:00. The results showed that the glucocorticoids had no significant effect on the relative expression of mTOR pathway-related genes at 8:00(before foodintake). After refeeding 1h, glucocorticoids significantly increased the relative expression of PI3Cα, and tend to increase the relative expression of PI3Cβand EEF2. But no sinificant effect on the other factors. Compared with control treatment, the mRNA level of mTOR pathway-related genes were no significant changes in trial 2.
In experiment 2, 48 male AA broilers with similar body weight were divided into 4 groups randomly, there were 6 repetitions in every group with 2 broilers in every repetition, rearing in separate cage. In group 1, male AA broilers were subcutaneous injected with DEX (2.6 mg/kg BW) at 6:00 from 11 to 13 days old ,and diets were high energy (ME, 3.6kcal/kg; CP, 20%), Group 2 is control group, Saline was injected with a suitable dose ,and diets were high energy, treats were the same as in group 1 except that dexamethasone was displaced by saline. Group 3 animals were injected by DEX and diets were low energy(ME, 2.6kcal/kg; CP, 20%), in group 4, animals were injected by saline, and diets were low energy. At the day of 13, samples (blood and hypothalamus) were obtained at 8:00 and 9:00 (GroupA and B were feed by high energy food, and Group C and D were feed by the same quality low energy food with Group A and B). The results showed that glucocorticoids had no significant effect on the relative expression of NPY, GR, INSR, AKT3, 4EBP1, mTOR, AgRP, POMC before and after ingestion in the stage of low energy diets. The glucocorticoids tend to reduce relative expression of GR, and tend to increase the relative expression of AgRP, in the low energy diet groups. In the stage of high energy diets, the glucocorticoids increased the relative expression of INSR, AKT3, 4EBP1(P<0.05), and the relative expression of POMC trend to decrease. All the effects vanished after refeed. there was no significant effect of glucocorticoids on relative expression of NPY, GR, mTOR, AgRP before and after ingestion in the stage of high energy diets.
In part 2, The broilers were randomly assigned to 6 group, 8 birds per group. After 21h fasting at 6:00, three groups (A, B, C) were injected by DEX in a dose of 2.6 mg/kg.BW, and another three group(A’, B’, C’) were treated with same dose saline. At the day of 11, blood and hypothalamus of Group A and A’were obtained at 9:00, at the same time the animals of Group B and B’were feed by high energy diets, the animals of Group C and C’were feed by low energy diets. At 10:00 all the blood samples were obtained, and hypothalamus were quick-freezed in liquid nitrogen. The results showed that glucocorticoids had no significant effect on the relative expression of AgRP, NPY, POMC, GR, Ghrelin, MC4R, INSR after fasting for 24h. The glucocorticoids significant increased the relative expression of NPY(P<0.01), and no significant changes of AgRP, POMC, GR, Ghrelin, MC4R, INSR were found. In the DEX-treated group the relative expression of NPY trend to increase at the stage of 1h refeeding of low energy diets, and there were no significant changes of the relative expression of AgRP, POMC, GR, Ghrelin, MC4R, INSR.
引文
龚德华.糖皮质激素作用机制的新进展,肾脏病与透析肾移植杂志,2002,9(1):62-64.
黄之瑜,孙志娟,范少光.肥胖与神经调节.生理科学进展.2001,32( 1):47-52.
姜华,张学军. PKB/Akt:一个具有多种功能的蛋白激酶.生命科学,2004,16:148-153,164.
孔雪.应激对家禽采食量调控的机制,山东农业大学硕士学位论文,2010. 刘华珍,彭克美.不同能量条件鸭下丘脑5-羟色胺样神经元的免疫组化研究.湖北畜牧兽
医文集.武汉:湖北科学技术出版社,2002,544-546.
卢庆萍,张宏福.动物应激的研究进展.动物营养学报,2007,19:465-468.
王镜岩等.生物化学,高等教育出版社,2002,423-425.
王兰芳,林海,杨全明等.日粮维生素A水平对免疫接种及热应激下蛋鸡脂质过氧化反应的影响.畜牧兽医学报,2002,33(5):443-447.
闫磊,慕晓玲.胰高血糖素样肽1与干细胞定向分化.中国生物工程杂志, 2007,27(4):115-119.
袁磊,应激对肉仔鸡采食量影响极其调节机制,山东农业大学博士学位论文,2007.
袁向飞,陆敏. Ras/MAPK与PI3K/Akt信号转导通路及其相互作用.国际检验医学杂志,2006,27:261-263.
张月萍,于建军.摄食控制的神经体液机制研究进展.中国神经科学志.2001.17(4):350-342.
周吕主编.胃肠生理学-基础与临.北京:科学出版社,166.
朱华栋等.肾上腺皮质激素的生理、药理作用,中国临床医生,2001,29(10):7-8.
Adam TC, Epel ES. Stress, eating and the reward system. Physiology and Behavior, 2007, 91: 449-458.
Aguilar-Bryan L, Bryan J. Molecular biology of adenosine triphosphate-sensitive potassium channels. Endocr. Rev., 1999, 20(2): 101-135.
Ammar AA, Sederholm F, Saito TR. NPY leptin:opposing effects on appetitive and consummatory ingestive behavior and sexual be havior. Physiol Regul Integr Comp Physiol, 2000, 278(6): 1627-1633.
Ashwell C, Czerwinski SM, Brocht DM, McMurtry JP. Hormonal regulation of leptin expression in broiler chickens. Am. J. Physiol., 1999, 276: 226–232.
Baudet ML, Harvey S. Ghrelin-induced GH secretion in domestic fowl in vivo and in vitro. J. Endocrinol, 2003, 179: 97–105.
Benoit SC, Air EL, Coolen LM, Strauss R, Jackman A, Clegg DJ, Seeley RJ, Woods SC. Thecatabolic action of insulin in the brain is mediated by melanocortins. J. Neurosci., 2002, 22: 9048-9052.
Bernier NJ, Peter RE. The hypothalamic-pituitary-interregnal axis and the control of food intake in teleost Wsh. Comp. Biochem. Physiol., 2001a, 129: 639–644.
Biondi CA, Gartside MG, Waring P, Lof?er KA, Stark MS, Magnuson MA, Kay GF, and Hayward NK. Conditional inactivation of the MEN1 gene leads to pancreatic and pituitary tumorigenesis but does not affect normal development of these tissues. Mol. Cell. Biol. 2004, 24: 3125–3131.
Bjorntorp P. Do stress reactions cause abdominal obesity and comorbidities? Obes Rev., 2001, 2: 73-86.
Boggiano MM, Chandler PC, Viana JB, Oswald KD, Maldonado CR, Wauford PK. Combined dieting and stress evoke exaggerated responses to opioids in binge-eating rats. Behav Neurosci., 2005, 119: 1207-1214.
Boswell T, Takeuchi S. Recent developments in our understanding of the avian melanocortin system: Its involvement in the regulation of pigmentation and energy homeostasis.
Peptides, 2005, 26: 1733–1743. Britton DR, Hoffman DK, Lederis K, Rivier J. A comparison of the behavioral effects of CRF, Sauvagine and Urotensin I. Brain Res. 1984,304, 201–205.
Brown EJ, Beal PA, Keith CT, Chen J, Shin TB & Schreiber SL. Control of p70s6 kinase by kinase activity of FRAP in vivo. Nature , 1995, 377: 441–446.
Cavagnini F, Croci M, Putignano P, Petroni ML, Invitti C. Glucocorticoids and neuroendocrine function. Int J Obes Relat Metab Disord., 2000, 24(Suppl 2): 77-79.
Considine RV, Caro JF. Leptin and the regulation of body weight. Int J Biochem Cell Biol, 1997, 29: 1255-1272.
Cota D, Proulx K, Smith KA, Kozma SC, Thomas G, Woods SC, Seeley RJ. Hypothalamic mTOR signaling regulates food intake. Science, 2006, 312(5775): 927-930.
Daniela Cota, Emily K. Matter, Stephen C. Woods, and Randy J. Seeley. The role of hypothalamic mammalian target of rapamycin complex 1 signaling in dietinduced obesity. The Journal of Neuroscience,2008,28(28):7202-7208.
Cota D, Proulx K, Smith KAB, Kozma SC, Thomas G, Woods SC and Seeley RJ. Hypothalamic mTOR signaling regulates food intake. Science, 2006, 312(5775):927-930.
Dallman MF, Pecoraro N, Akana SF, La Fleur SE, Gomez F, Houshyar H, Bell ME, Bhatnagar S, Laugero KD, Manalo S. Chronic stress and obesity: a new view of“comfort food.”Proc Natl Acad Sci USA, 2003, 100: 11696–11701.
Dallman MF, Akana SF, Laugero KD, Gomez F, Manalo S, Bell ME, Bhatnagar S. A spoonful of sugar: feedback signals of energy stores and corticosterone regulate responses to chronic stress. Physiol Behav 2003, 79: 3–12.
Denbow DM. Peripheral regulation of food intake in poultry. J. Nutr., 1994, 124:1349–1354. Denbow DM, Snapir N, Furuse M. Inhibition of food intake by CRF in chickens. Physiol Behav. 1999,66: 645–649.
Devenport L, Stith R., Mimicking corticosterone’s daily rhythm with specific receptor agonists : Effects on food, water, and sodium intake. Elsevier Science Inc, 1992, 51(6): 1247-1255.
Dridi S, Swennen Q, Decuypere E, Buyse J. Mode of leptin action in chicken hypothalamus. Brain Res., 2005, 1047: 214–223.
Drolet G, Dumont EC, Gosselin I, Kinkead R, Laforest S, Trottier JF. Role of endogenous opioid system in the regulation of the stress response. Prog Neuropsychopharmacol Biol Psychiatry., 2001, 25: 729-741.
Dryden S, Frankish H, Qiong W. Neuropeptide Y and energy balance:one way ahead for the treatment of obesity.Europen Journal of CIinical Investigation,1994, 24: 293—308.
Farooqi IS, Keogh JM, Yeo GS, Lank EJ, Cheetham T, O’Rahilly S. Clinical spectrum of obesity and mutations in the melanocortin 4 receptor gene. N Engl J Med., 2003, 348(12): 1085-1095.
Flier JS. Regulating energy balance: the substrate strikes back. Science, 2006, 312(5775): 861-864.
Forbes S, Bui S, Robinson BR, Hochgeschwender U, Brennan MB. Integrated control of appetite and fatmetabolism by the leptin-proopiomelanocortin pathway. Proc. Natl. Acad. Sci. USA, 2001, 98: 4233–4237.
Friedman J, Halaas JL, Leptin and the regulation of body weight.Nature, 1998, 395: 763-770. Fulton S, Woodside B, Shizgal P. Modulation of brain reward circuitry by leptin. Science, 2000, 287: 125-128.
Furuse M, Matsumoto M, Saito N, Sugahara K, Hasegawa S. The central
corticotropin-releasing factor and glucagon-like peptide-1 in food intake of the neonatal chick. Eur. J. Pharmacol. 1997, 339: 211–214.
Furuse M, Tachibana T, Ohgushi A, Ando R, Yoshimatsu T and Denbow DM. Intracerebroventricular injection of ghrelin and growth hormone releasing factor inhibitsfood intake in neonatal chicks. 2001, Neuroscience letters 301, 123-126.
Gehlert DR. Subtypes of receptors for neuropeptide Y: Implications for the targeting of therapeutics. Life Sci 1994, 55:551-562.
Gerets HH, Peeters K, Arckens L, Vandesande F, Berghman LR. Sequence and distribution of pro-opio-melanocortin in the pituitary and the brain of the chicken(Gallus gallus). J. Comp. Neurol., 2000, 417: 250–262.
Gingras AC, Raught B, Sonenber GN. Regulation of translation initiation by FRAP/mTOR. Genes Dev, 2001, 15: 807-826.
Giraudo SQ, Grace MK, Billington CJ, Levine AS. Differential effects of neuropeptide Y and the mu-agonist DAMGO on‘palatability’vs.‘energy’. Brain Res., 1999, 834: 160-163.
Gourine AV, Melenchuk EV, Poputnikov DM, Gourine VN, Spyer KM. Involvement of purinergic signalling in central mechanisms of body temperature regulation in rats. Br. J. Pharmacol., 2002, 135(8): 2047-2055.
Gray TS, Morley JE. Neuropeptide Y: anatomical distribution and possible function in mammalian nervous system. Life Sci. 1986, 38: 389–401.
Hanada M, Fengj H, Hemmings BA. Structure, regulation and function of PKB/Akt-a major therapeutic target. Biochim Biophysica Acta, 2004, 1697: 3-16.
Hardie DG, Carling D&Carlson M. The AMP-activated/SNF1 protein kinase subfamily: metabolic sensors of the eukaryotic cell, Annu. Rev. Biochem.1998, 67: 821–855.
Hardie DG, Hawley SA, Scott JW. AMP-activated protein kinase development of the energy sensor concept. J. Physiol., 2006, 574: 7–15.
Harrold JA, Williams G, Widdowson PS. Changes in hypothalamic agouti-related protein (AGRP), but not alpha-MSH or pro-opiomelanocortin concentrations in dietary-obese and food-restricted rats. Biochem Biophys Res Commun, 1999, 258(3): 574–577.
Heatherton TF, Baumeister RF. Binge eating as escape from self-awareness. Psychol Bull, 1991, 110(1): 86-108.
Heilig M. The NPY system in stress, anxiety and depression. Neuropeptides, 2004, 38: 213-224.
Heinrichs SC, Richard D. The role of corticotrophin releasing factor and urocortin in the modulation of ingestive behavior. Neuropeptides, 1999, 33(5): 350–359.
Herman JP, Figueiredo H, Mueller NK, Ulrich-Lai Y, Ostrander MM, Choi DC, Cullinan WE. Central mechanisms of stress integration: hierarchical circuitry controlling hypothalamo–pituitary–adrenocortical responsiveness. Front Neuroendocrinol., 2003, 24(3): 151-180.
Honda K, Kamisoyama H, Saneyasu T, Sugahara K, Hasegawa S. Central administration of insulin suppresses food intake in chicks. Neuroscience Letters, 2007, 423: 153-157.
Jewett DC, Cleary JP, Levine AS, Schaal DW, Thompson T. Effects of neuropeptide Y, insulin, 2-deoxyglucose, and food deprivation on food-motivated behavior. Psychopharmacology(Berl), 1995, 120: 261-271.
Jonson L, Schoeman N, Saayman H. Identification of ostrich and chicken cholecystokinin cDNA and intestinal peptides. Peptides, 2000,21(9): 1337-1344.
Kanatani A, Ishihara A, Asahi S. Potent neuropeptide Y-Y, receptor antagonist. Blockade of neuropeptide Y-induced and physiological food intake. Endocrinology, 1996, 137: 3177-3182.
Kapoor JR, Sladek CD. Purinergic and adrenergic agonists synergize in stimulating vasopressin and oxytocin release. J. Neurosci., 2000, 20: 8868-8875.
Kawakami S, Bungo T, Ando R, Ohgushi A, Shimojo M, Masuda Y, Furuse M. Central administration of alpha-melanocyte stimulating hormone inhibits fasting- and neuropeptide Y-induced feeding in neonatal chicks. Eur. J. Pharmacol., 2000, 398: 361–364.
Kemp BE, Mitchelhill KI, Stapleton D, Michell BJ, Chen ZP & Witters LA. Dealing with energy demand: the AMP-activated protein kinase. Trends. Biochem. Sci. 1999, 24: 22–25.
Kimball SR, Orellana RA, O'Connor PMJ, Suryawan A, Bush JA, Nguyen HV, Thivierge MC, Endotoxin induces differential regulation of mTOR-dependent signaling in skeletal muscle and liver of neonatal pigs. American Journal of Physiology-Endocrinology And Metabolism, 2003. 285(3): E637-E644.
Kitraki E, Soulis G. Impaired Neuroendocrine Response to Stress following a Short-Term Fat-Enriched Diet. Neuroendocrinology, 2004, 79: 338- 345
Kreek MJ, Koob GF. Drug dependence: stress and dysregulation of brain reward pathways. Drug Alcohol Depend, 1998, 51: 23-47.
Kuenzel WJ, Douglass LW, Davison BA. Robust feeding following central administration of neuropeptide Y or peptide YY in chicks, Gallus domesticus. Peptides, 1987, 8: 823-828.
Kuenzel WJ, McMurtry J. NeuropeptideY: brain localization and central effects on plasma insulin levels in chicks. Physiol Behav, 1988, 44: 669–678.
Lawrence JC. PHAS/4E-BPs as regulators of mRNA translation and cell proliferation. Trends. Biochem. Sci. 1997,22: 345–349.
Lei Bi, Ichiro Okabe, David J. Bernard, Robert L. Nussbaum, Early embryonic lethality inmice deficient in the p110βcatalytic subunit of PI 3-kinase. Mammalian Genome, 2002, 13: 169–172.
Levin BE, Dunn-Meynell AA, Routh VH. CNS sensing and regulation of peripheral glucose levels. Int. Review Neurobiol., 2002, 51: 219-258.
Levine AS, Jewett DC, Cleary JP, Kotz CM, Billington CJ. Our journey with neuropeptideY: effects on investive behaviors and energy expenditure. Peptides, 2004, 25: 505-510.
Maeda N, Shimomura I, Kishida K, Nishizawa H, Matsuda M, Nagaretani H, Furuyama N, Kondo H, Takahashi M and Arita Y. Diet-induced insulin resistance in mice lacking adiponectin/ACRP30. Nature Medicine,2002,8:731-737.
Mayer J, Thomas DW. Regulation of food intake and obesity. Science, 1967, 156, 773: 328-337.
McCurdy MC, Barbut S, Quinton M, Sea-. sonal effects on PSE in young turkey breast. meat, Food Res. Int. 1996, 29: 363–366.
McKee SR and AR Sams. The effect of seasonal heat stress on rigor development and the incidence of pale, exudative turkey meat. Poult. Sci. 1997, 76: 1616–1620.
Minokoshi Y, Alquier T, Furukawa N, Kim YB, Lee A, Xue B, Mu J, Foufelle F, FerréP, Birnbaum MJ, Stuck BJ, Kahn BB..AMP kinase regulates food intake by responding to hormonal and nutrient signals in the hypothalamus.Nature, 2004, 428(6982): 569-574.
Mobbs CV, Kow LM, Yang XJ. Brain glucose-sensing mechanisms: ubiquitous silencing by aglycemia vs. hypothalamic neuroendocrine responses. Am. J. Physiol Endocrinol Metab., 2001, 281(4) : 649-654.
Moreau J, Kilpatrick G, JenckF Urocortin, a novel neuropeptide with anxiogenic-like properties. NeuroReport.1997, 8:1697–1701.
Mori H, Inoki K, M¨nzberg H, Opland D, Faouzi M, Villanueva EC, Ikenoue T, Kwiatkowski D, MacDougald OA and Myers JMG. Critical role for hypothalamic mTOR activity in energy balance. Cell Metab, 2009, 9(4): 362-374.
Morley JE, Hernandez EN, Flood JF. Neuropeptide Y increases food intake in mice. Am. J. Physiol. 1987, 253: R516–R522.
Mothe-Satney I, Gautier N, Hinault C, Lawrence JC, Van Obberghen E: In rat hepatocytes glucagon increases mammalian target of rapamycin phosphorylation on serine 2448 but antagonizes the phosphorylation of its downstream targets induced by insulin and amino acids. Journal of Biological Chemistry , 2004, 279(41): 42628.
O’Hare E, Shaw DL, Tierney KJ, E-M K, Levine AS, Shephard RA. Behavioral and neurochemical mechanisms of the action of mild stress in the enhancement of feeding.Behav. Neurosci., 2004, 118(1): 173-177.
Ollmann MM, Wilson BD, Yang YK, Kerns JA, Chen Y, Gantz I, Barsh GS. Antagonism of central melanocortin receptors in vitro and in vivo by agouti-related protein. Science, 1997, 278(5335): 135–138.
Pecoraro N, Reyes F, Gomez F, Bhargava A, Dallman MF. Chronic stress promotes palatable feeding, which reduces signs of stress: feedforward and feedback effects of chronic stress. Endocrinology, 2004, 145(8): 3754-3762.
Pene F, Claessens YE, Muller O, Viguie F, Mayeux P, Dreyfus F, Lacombe C, Bouscary D. Role of the phosphatidylinositol 3-kinase/Akt and mTOR/P70S6-kinase pathways in the proliferation and apoptosis in multiple myeloma. Oncogene 21, 2002: 6587-6597.
Peters A, Schweiger U, Pellerin L, Hubold C, Oltmanns KM, Conrad M, Schultes B, Born J, Fehm HL. The selfish brain: competition for energy resources. Neuroscience and Biobehavioral Reviews, 2004, 28: 143-180.
Phillips-Singh D, Li Q, Takeuchi S, Okubo T, Sharp PJ, Boswell T. Fasting differentially regulates expression of agouti-related peptide, pro-opiomelanocortin, pre-pro-orexin, and vasoactive intestinal polypeptide mRNAs in the hypothalamus of Japanese quail. Cell Tissue Res., 2003, 313: 217–225.
Pitel F, Monbrun C, Gellin J, Vignal A. The chicken LEP (OB) gene has not been mapped. Anim. Genet., 2000, 31: 281.
Plum L, Belgardt BF and Bruning JC. Central insulin action in energy and glucose homeostasis. Journal of Clinical Investigation 2006 , 116:1761-1767.
Pocai A, Muse ED and Rossetti L. Did a muscle fuel gauge conquer the brain? Nature Medicine 2006, 12: 50-51.
Proszkowiec-Weglarz M, Richards MP, Ramachandran R, McMurtry JP. Characterization of the AMP-activated protein kinase pathway in chickens. Comp. Biochem. Physiol. B Biochem. Mol. Biol., 2006, 143: 92–106.
Proulx K, Cota D, Woods SC and Seeley RJ. Fatty acid synthase inhibitors modulate energy balance via mammalian target of rapamycin complex 1 signaling in the central nervous system. 2008, 57(12), 3231-3238.
Rada P, Avena NM, Hoebel BG. Daily bingeing on sugar repeatedly releases dopamine in the accumbens shell. Neuroscience, 2005, 134: 737-744.
Ramos EJ, Meguid MM, Campos AC, Coelho JC. Neuropeptide Y, alpha-melanocyte-stimulating hormone, and monoamines in food intake regulation. Nutrition, 2005, 21(2): 269-279.
Raver N, Taouis M, Dridi S, Derouet M, Siomon J, Robinzon B, Djiane J and Gertler A. Large scale preparation of biological active recombinant chicken obese protein (Leptin) .Protein Expression and Purification.1998, 14: 403-408.
Richards MP, Poch SM, Ashwell CM. Identification and expression of the turkey leptin receptor. Poult Sci., 2001, 80: 394-399.
Richards MP, Poch SM, Coon CN, Rosebrough RW, Ashwell CM and McMurtry JP. Feed restriction significantly alters lipogenic gene expression in broiler breeder chickens. The Journal of nutrition 133, 2003,707-715.
Roh C, Han J, Tzatsos A,et al. Nutrient sensing mTORmediated pathway regulates leptin production in isolated rat adipocytes. Am J Physiol Endocrinol Metab,2003, 284(2): E322-330.
Sahu A. A hypothalamic role in energy balance with special emphasis on leptin. Endocrinology,2004, 145(6):2613-2620.
Schwartz MW, Woods SC, Porte D, Seeley RJ, Baskin DG. Central nervous system control and food intake. Nature, 2000, 404:661-671.
Simon J, Leroith D. Insulin receptors of chicken liver and brain. Characterization of alpha and beta subunit properties. Eur. J. Biochem., 1986, 158: 125–132.
Stanley BG, Magdalin W, Seirafi A, Nguyen MM, Leibowitz SF. Evidence for neuropeptide Y mediation of eating produced by food deprivation and for a variant of the Y receptor mediating this 1 peptide’s effect. Peptides . 1992, 13: 581–587.
Stephen C. Woods, Randy J. Seeley, and Daniela Cota. Regulation of Food Intake Through Hypothalamic Signaling Networks Involving mTOR, Annu. Rev. Nutr. 2008.28: 295-311.
Tache Y, Maeda–Hagiwara M, Turkelson CM. Central nervous system action of corticotropin-releasing factor to inhibit gastric emptying in rats. Am. J. Physiol. 1987, 253: G241–G245.
Tachibana T, Sugahara K, Ohgushi A, Ando R, Kawakami S, Yoshimatsu T, Furuse M. Intracerebroventricular injection of agouti-related protein attenuates the anorexigenic effect of alpha-melanocyte stimulating hormone in neonatal chicks. Neurosci Lett., 2001, 305: 131–134.
Takeuchi S, Teshigawara K, Takahashi S. Wide spread expression of agouti-related protein (AGRP) in the chicken: A possible involvement of AGRP in regulating peripheral melanocortin systems in the chicken. Biochim. Biophys. Acta., 2000, 1496: 261–269.
Tatemoto K. Isolation and characterization of peptide YY PYY , a candidate gut hormone thatinhibits pancreatic exocrine function. Proc. Natl. Acad. Sci. U. S. A.1982a, 79: 2514–2518.
Tesseraud S, Abbas M, Duchene S, Bigot K, Vaudin P, Dupont J. Mechanisms involved in the nutritional regulation of mRNA translation: Features of the avian model. Nutr. Res. Rev., 2006, 19: 104–116.
Torres SJ, Nowson CA. Relationship between stress, eating behavior, and obesity. Nutrition, 2007, 23: 887-894.
Vanhaesebroeck B, Welham MJ, Kotani K, Stein R, Warne PH, Zvelebil MJ, Higashi K, Volinia S, Downward J, Waterfield MD..P110 delta, a novel phosphoinositide 3-kinase in leukocytes. ProcNatl Acad Sci USA ,1997: 4330–4335.
Vannucci SJ, Seaman LB, Brucklacher RM, Vannucci RC. Glucose transport in developing rat brain: glucose transporter proteins, rate constants and cerebral glucose utilization. Mol. Cell. Biochem., 1994, 140: 177-184.
Vettor R, Fabris R, Pagano C, Federspil G. Neuroendocrine regulation of eating behaviour. J Endocrinol Invest., 2002, 25: 836-854.
Viollet B, Mounier R, Leclerc J. Targeting AMP-activated protein kinase as a novel therapeutic approach for the treatment of metabolic disorders. Diabetes Metab, 2007, 33: 395-402.
Volkow ND, Wise RA. How can drug addiction help us understand obesity? Nat Neurosci., 2005, 8(5): 555-560.
Ward SG, Finan P. Isoform specific phosphoinositide 3-kinase inhibitors as therapeutic agents. Curr Opin Pharmacol, 2003, 3: 426-434. Woods SC, Benoit SC, Clegg DJ. The brain-gut-islet connection. Diabetes, 2006, 55: 114–121.
Woods SC, Seeley RJ, Porte Jr D, Schwartz MW. Signals that regulate food intake and energy homeostasis. Science, 1998, 280: 1378–1383.
Woods SC. Gastrointestinal satiety signals. An overview of gastrointestinal signals that in?uence food intake. Am J Physiol Gastrintest Liver Physiol., 2004, 286: 7-13.
Woods SC, Seeley RJ and Cota D. Regulation of food intake through hypothalamic signaling networks involving mTOR.Annu Rev Nutr, 2008, 28: 295-311.
Wullschleger S, Loewith R, Hall MN. TOR signaling in growth and metabolism. Cell, 2006, 124: 471–484.
Wymann MP, Pirola L. Structure and function of phosphoinositide 3-kinases. Biochim Biophys Acta ,1998, 1436: 127–150.
Xu AW, Kaelin CB, Takeda K, Akira S, Schwartz MW, Barsh GS. PI3K integrates the action of insulin and leptin on hypothalamic neurons. J Clin Invest., 2005, 115(4): 951-958.
Yuan J, Liu W, Liu Z L, Li N. cDNA cloning, genomic structure, chromosomal mapping and expression analysis of ADIPOQ (adiponectin) in chicken. Cytogenet Genome Res, 2006, 112(1-2): 148-151.
Zarjevski N, Cusin I, Vettor R, Rohner-Jeanrenaud F, Jeanrenaud B. Chronic intracerebroventricular neuropeptide-Y administration to normal rats mimics hormonal and metabolic changes of obesity. Endoocrinology, 1993, 133: 1753-1758.
Zhang R, Nakanishi T, Ohgushi A, Ando R, Yoshimastsu T, Denbow DM, Furuse M, Suppression of food intake induced by corticotrophin-releasing factor family in neonatal chicks. Eur. J. Pharmacol. 2001, 427: 37-41.
