运动对肥胖大鼠摄食量和体重影响及机制研究
摘要
研究目的:
一次性运动和长期运动对肥胖大鼠摄食以及血浆和下丘脑相关摄食内分泌指标的影响,初步探讨运动减肥的神经内分泌机制。
研究方法:
实验动物与分组:10周营养性肥胖建模成功SD大鼠。一次性运动实验分为即刻、1h、3h、12h、24h和对照组,长期运动实验分为长期运动组和长期对照组。
实验动物运动方式:大鼠专用电动跑台,坡度5%,速度20m/min,运动时间40分钟。一次性运动实验在肥胖大鼠运动后不同时间段取材,长期运动实验肥胖大鼠运动8周,每周5次,在最后一次运动结束后24小时取材。
样本测试:全自动生化分析仪测试肥胖大鼠血糖、甘油三酯、胆固醇、HDL、LDL;RIA方法测试血浆和下丘脑ghrelin、obestatin、NPY蛋白表达;RT-PCR方法测试下丘脑ghrelin受体GHSR-1a、obestatin受体GPR-39和NPY基因表达。
研究结果:
1、肥胖大鼠血浆ghrelin和Ghrelin/Obestatin比值有下降趋势,NPY显著升高;下丘脑ghrelin和obestatin显著下降,Ghrelin/Obestatin比值显著上升,而NPY有下降趋势。GHSR-1a基因表达显著下降,而NPY基因表达没有明显变化,GPR-39 mRNA在下丘脑没有表达;
2、一次性运动后,肥胖大鼠摄食量显著下降,12h开始恢复;血糖等基础指标下降,在3h开始恢复;运动后不同时间段血浆ghrelin和obestatin没有变化,但可以降低NPY浓度;
3、一次性运动后,肥胖大鼠下丘脑ghrelin和obestatin在12h之前降低,然后急剧升高,在24h恢复;NPY在运动后开始升高,在24h恢复;GHSR-1a和NPY基因表达没有影响,GPR-39基因没有表达;
4、8周跑台运动后,肥胖大鼠血浆ghrelin和obestatin没有影响;下丘脑ghrelin和obestatin显著下降,NPY显著升高;GHSR-1a基因表达没有影响,NPY基因表达显著增加。
结论:
1、Ghrelin可能通过中枢机制影响摄食和能量代谢调节;
2、Obestatin-GPR39通路在能量代谢调节中可能不起作用;
3、下丘脑Ghrelin/Obestatin比值在大鼠肥胖发生中可能有一定的作用。
Aims:Research the effects of food intake related endocrinological hormones on serum and hypothalamic of obese rats by acute and long time of exercise and discuss the neuroendocrinology mechanisms of weight loss by exercise.
Methods:Diet induced obese rats go throuth two experimental models: acute exercise experiment and 8 weeks exercise experiment.The rats run at a speed of 20 m min-1,50 slope on the treadmeal for 40 min one times on the acute experimental model and every five days for 8 weeks on the chronic experimental model.On the day they were sacrificed,rats from the acute experimental exercise group were randomly divided into six subgroups,namely C,EO,E1,E3,E12 and E24,which respectively were named as the preexercise control group,0 min postexercise group,one hour postexercise group,three hour postexercise group,twele hour postexercise group and twenty hour postexercisegroup.On the chronic exercise experiment model,the rats are divided long exercise group and long control group and the rats had rest for 24 hours before they are sacrificed after the last day.We determined the concentrations of ghrelin,obestatin and NPY on serum and hypothalamic of obese rats at once,one hour,three hour,12 hour and 24 hour after acute exercise and the concentrations after eight weeks' exercise by using RIA;we also determined the receptor GHSR-1a mRNA of ghrelin,GPR-39 mRNA of obestatin and NPY mRNA on the hypothalamic tissues by RT-PCR.
Results:
1) Compared with normal weight rats,the obese rats had distinct differences on body weight,BMI and serum preferences.The concentration of ghrelin and the ratio of Ghrelin/Obestatin had a decline tendency on serum,obestatin had an up tendency and NPY was higher than the normal weight rats distinctly.But on the hypothalamic tissues,the concentrations of ghrelin and obestatin decreased greatly,the ratio of Ghrelin/Obestatin increased,NPY had a decline tendency lightly.The ghrelin receptor GHSR-1a mRNA decreased distinctly,NPY mRNA had no change and we couldn't find GPR-39 mRNA on hypothalamic.
2) After acute exercise,appetite and food size decreased greatly on obese rats and recovered at the point of 12 hours;Glu and other preferences on plasma decreased and recovered at the point of 3 hours;on every time points,the serum concentrations of ghrelin and obestatin had no changes, but NPY decreased distinctly.
3) After acute exercise,the concentrations of ghrelin and obestatin on hypothalamic decreased before the point of 12 hours,then they increased greatly and recovered to preexercise after 24 hours;NPY increased at once after exercise and recovered after 24 hours;The receptor GHSR-1a mRNA of ghrelin and NPY mRNA had no changes after exercise and we couldn't find GPR-39 mRNA on hypothalamic too.
4) After 8 weeks oxygen exercise,the obese rats expended a great deal energy with no food intake increased,on the contrast,their food size decreased greatly;Exercise alone had no effects on serum ghrelin and obestatin,but on hypothalamic,ghrelin and obestatin decreased distinctly,NPY increased greatly;The receptor GHSR-1a mRNA of ghrelin had no change,but NPY mRNA increased distinctly after exercise.
Conclusions:
1) Ghrelin mediated food intake and energy metabolism post exercise through hypothalamic centers.
2) Obestatin- GPR-39 may be had no use on energy homeostasis.
3) The ratio of Ghrelin/Obestatin must be very important on the etiology of obese rats.
一次性运动和长期运动对肥胖大鼠摄食以及血浆和下丘脑相关摄食内分泌指标的影响,初步探讨运动减肥的神经内分泌机制。
研究方法:
实验动物与分组:10周营养性肥胖建模成功SD大鼠。一次性运动实验分为即刻、1h、3h、12h、24h和对照组,长期运动实验分为长期运动组和长期对照组。
实验动物运动方式:大鼠专用电动跑台,坡度5%,速度20m/min,运动时间40分钟。一次性运动实验在肥胖大鼠运动后不同时间段取材,长期运动实验肥胖大鼠运动8周,每周5次,在最后一次运动结束后24小时取材。
样本测试:全自动生化分析仪测试肥胖大鼠血糖、甘油三酯、胆固醇、HDL、LDL;RIA方法测试血浆和下丘脑ghrelin、obestatin、NPY蛋白表达;RT-PCR方法测试下丘脑ghrelin受体GHSR-1a、obestatin受体GPR-39和NPY基因表达。
研究结果:
1、肥胖大鼠血浆ghrelin和Ghrelin/Obestatin比值有下降趋势,NPY显著升高;下丘脑ghrelin和obestatin显著下降,Ghrelin/Obestatin比值显著上升,而NPY有下降趋势。GHSR-1a基因表达显著下降,而NPY基因表达没有明显变化,GPR-39 mRNA在下丘脑没有表达;
2、一次性运动后,肥胖大鼠摄食量显著下降,12h开始恢复;血糖等基础指标下降,在3h开始恢复;运动后不同时间段血浆ghrelin和obestatin没有变化,但可以降低NPY浓度;
3、一次性运动后,肥胖大鼠下丘脑ghrelin和obestatin在12h之前降低,然后急剧升高,在24h恢复;NPY在运动后开始升高,在24h恢复;GHSR-1a和NPY基因表达没有影响,GPR-39基因没有表达;
4、8周跑台运动后,肥胖大鼠血浆ghrelin和obestatin没有影响;下丘脑ghrelin和obestatin显著下降,NPY显著升高;GHSR-1a基因表达没有影响,NPY基因表达显著增加。
结论:
1、Ghrelin可能通过中枢机制影响摄食和能量代谢调节;
2、Obestatin-GPR39通路在能量代谢调节中可能不起作用;
3、下丘脑Ghrelin/Obestatin比值在大鼠肥胖发生中可能有一定的作用。
Aims:Research the effects of food intake related endocrinological hormones on serum and hypothalamic of obese rats by acute and long time of exercise and discuss the neuroendocrinology mechanisms of weight loss by exercise.
Methods:Diet induced obese rats go throuth two experimental models: acute exercise experiment and 8 weeks exercise experiment.The rats run at a speed of 20 m min-1,50 slope on the treadmeal for 40 min one times on the acute experimental model and every five days for 8 weeks on the chronic experimental model.On the day they were sacrificed,rats from the acute experimental exercise group were randomly divided into six subgroups,namely C,EO,E1,E3,E12 and E24,which respectively were named as the preexercise control group,0 min postexercise group,one hour postexercise group,three hour postexercise group,twele hour postexercise group and twenty hour postexercisegroup.On the chronic exercise experiment model,the rats are divided long exercise group and long control group and the rats had rest for 24 hours before they are sacrificed after the last day.We determined the concentrations of ghrelin,obestatin and NPY on serum and hypothalamic of obese rats at once,one hour,three hour,12 hour and 24 hour after acute exercise and the concentrations after eight weeks' exercise by using RIA;we also determined the receptor GHSR-1a mRNA of ghrelin,GPR-39 mRNA of obestatin and NPY mRNA on the hypothalamic tissues by RT-PCR.
Results:
1) Compared with normal weight rats,the obese rats had distinct differences on body weight,BMI and serum preferences.The concentration of ghrelin and the ratio of Ghrelin/Obestatin had a decline tendency on serum,obestatin had an up tendency and NPY was higher than the normal weight rats distinctly.But on the hypothalamic tissues,the concentrations of ghrelin and obestatin decreased greatly,the ratio of Ghrelin/Obestatin increased,NPY had a decline tendency lightly.The ghrelin receptor GHSR-1a mRNA decreased distinctly,NPY mRNA had no change and we couldn't find GPR-39 mRNA on hypothalamic.
2) After acute exercise,appetite and food size decreased greatly on obese rats and recovered at the point of 12 hours;Glu and other preferences on plasma decreased and recovered at the point of 3 hours;on every time points,the serum concentrations of ghrelin and obestatin had no changes, but NPY decreased distinctly.
3) After acute exercise,the concentrations of ghrelin and obestatin on hypothalamic decreased before the point of 12 hours,then they increased greatly and recovered to preexercise after 24 hours;NPY increased at once after exercise and recovered after 24 hours;The receptor GHSR-1a mRNA of ghrelin and NPY mRNA had no changes after exercise and we couldn't find GPR-39 mRNA on hypothalamic too.
4) After 8 weeks oxygen exercise,the obese rats expended a great deal energy with no food intake increased,on the contrast,their food size decreased greatly;Exercise alone had no effects on serum ghrelin and obestatin,but on hypothalamic,ghrelin and obestatin decreased distinctly,NPY increased greatly;The receptor GHSR-1a mRNA of ghrelin had no change,but NPY mRNA increased distinctly after exercise.
Conclusions:
1) Ghrelin mediated food intake and energy metabolism post exercise through hypothalamic centers.
2) Obestatin- GPR-39 may be had no use on energy homeostasis.
3) The ratio of Ghrelin/Obestatin must be very important on the etiology of obese rats.
引文
[1]King NA,Lluch A,Stubbs RJ,et al.High dose exercise does not increase hunger or energy intake in free living males.Eur J Clin Nutr,1997,51(7):478-483
[2]Melanie S.Moorel,Caroline J.Dodd,Joanne R.Welsman,et al.Short-term appetite and energy intake following imposed exercise in 9-to 10-year-old girls.Appetite,2004(43):127-134
[3]Maraki F,Tsofliou YP,Pitsiladis,et al.Acute effects of a single exercise class on appetite,energy intake and mood.Is there a time of day effect?Appetite,2005(45):272-278
[4]Hubert P,King NA,Blundell JE.Uncoupling the effects of energy expenditure and energy intake:Appetite response to short-term energy deficit induced by meal omission and physical activity.Appetite,1998(31):9-19
[5]Thompson DA,Wolfe LA,Eikelboom R,et al.Acute effects of exercise intensity on appetite in young men.Med Sci Sports Exerc,1988,20(3):222-227
[6]Stubbs RJ,Sepp A,Hughes DA,et al.The effect of graded levels of exercise on energy intake and balance in free-living women.International Journal of Obesity,2002(26):866-869
[7]King NA,Burley VJ,Blundell JE.Exercise-induced suppression of appetite:Effects on food intake and implications for energy balance.Eur.J Clin Nutr,1994 (48):715-724
[8]King NA,Blundell JE.High-fat foods overcome the energy expenditure induced by high-intensity cycling or running.European Journal of Clinical Nutrition,1995 (49):114-123
[9]Westerterp MS,Verwegen CR,Ijedema MJ,et al.Acute effects of exercise or sauna on appetite in obese and nonobese men.Physiology and Behavior,1997 (62):1345-1354
[10]Harry RK,FXavier PS,Karen S,et al.Acute effects of exercise on food intake in obese and nonobese women.Am J Clin Nuir,1990(52):240-245
[11]George,VA,Morganstein A.Effect of moderate intensity exercise on acute enrgy intake in normal and overweight females.Appetite,2003 (40):43—46
[12]Pomerleau M,Imbeault P,Parker T.Effects of exercise intensity on food intake and appetite in women.Am J Clin Nutr,2004;80(5):1230-1236
[13]Woo R,Garrow JS,Pi-Sunyer FX.Effect of exercise on spontaneous calorie intake in obesity.Am J Clin Nutr,1982;36(3):470-477
[14]Westerterp KR,Saris WHM,Van EM,et al.Use of doubly labelled water technique in humans during heavy sustained exercise.J Appl Physiol,1986(61):2162-2167
[15]Verger P,Lanteaume MT,Louis-Sylvestre J.Human intake and choice of foods at intervals after exercise.Appetite,1992(18):93-99
[16]Verger P,Lanteaume MT,Louis-Sylvestre J.Free food choice after acute exercise in men.Appetite,1994(22):159-164
[17]Donnelly JE,Jacobsen DJ,Heelan KS,et al.The effects of 18 months of intermittent vs.continuous exercise on aerobic capacity,body weight and composition,and metabolic fitness in previously sedentary,moderately obese females.Int J Obes Relat Metab Disord,2000;24(5):566-572
[18]Donnelly JE,Kirk EP,Jacobsen DJ,et al.Effects of 16 mo of verified,supervised aerobic exercise on macronutrient intake in overweight men and women:the Midwest exercise trial.Am J Clin Nutr,2003;78(5):950-956
[19]Katarina Melzera,Bengt Kayserb,Wim HM Saris,et al.Effects of physical activity on food intake.Clinical Nutrition,2005;24(6):885-895
[20]Stubbs RJ,Hughes DA,Johnstone AM,et al.A decrease in physical activity affects appetite,energy,and nutrient balance in lean men feeding ad libitum,Am J Clin Nutr.2004;79(l):62-69
[21]Murgatroyd PR,Goldberg GR,Leahy FE,et al.Effects of inactivity and diet composition on human energy balance.Int J Obes Relat Metab Disord,1999;23(12):1269-1275
[22]Blundell JE,King NA.Physical activity and regulation of food intake:current evidence.Med Sci Sports Exerc,1999;31(ll):573-583
[23]Blundell JE,King NA.Exercise,appetite control,and energy balance,Nutrition.2000 (16):519-522
[24]Schwartz MW,Woods SC,Seeley RJ,et al.Is the energy homeostasis system inherently biased toward weight gain?Diabetes,2003(52):232-238
[25]Stephen C.Woods,Randy J.Seeley.Adiposity Signals and the Control of Homeostasis.Nutrition,2000;16(10):894-902
[26]George A.Bray.A Concise Review on the Therapeutics of Obesity Nutrition,2000(16):953-960
[27]Zhang JV,Ren PG,Avsian-Kretchmer O,et al.Obestatin,a peptide encoded by the ghrelin gene,opposes ghrelin's effects on food intake.Science,2005;310(5750):996-999
[28]Christopher G.Bell,Andrew J.Walley,Philippe Froguel.The genetics of human obesity.Nature Review,2005,3:221-234
[29]Kojima M,Hosoda H,Date Y,et al.Ghrelin is a growth-hormone-releasing acylated peptide from stomach.Nature,1999;402(6762):656-660
[30]Hosda H,Kojima M,Matasuo H,et al.Ghrelin and desacyl ghrelin:two major forms of rat ghrelin peptide in gastrointestinal tissue.Biochem Biophys Res Commun,2000;279(3):909-913
[31]Date Y,Kojima M,Hosoda H,et al.Ghrelin,a novel growth hormone-releasing acylated peptide,is synthesized in a distinct endocrine cell type in the gastrointestinal tracts of rats and humans.Endocrinology,2000(141):4255-4261
[32]Muccioli G,Tschop M,Papotti M,et al.Neuroendocrine and peripheral activities of ghrelin:implications in metabolism and obesity.Eur J Pharmacol,2002(440):235-254
[33]Howard AD,Feighner SD,Cully DF,et al.A receptor in pituitary and hypothalamus that functions in growth hormone release.Science,1996(273):974-977
[34]Gnanapavan S,Kola B,Bustin SA,et al.The tissue distribution of the mRNA of ghrelin and subtypes of its receptor,GHS-R,in humans.J Clin Endocrinol Metab,2002(87):2988-2991
[35]Muccioli G,Ghe C,Ghigo MC,et al.Specific receptors for synthetic GH secretagogues in the human brain and pituitary gland.J Endocrinol,1998(157):99—106
[36]Papotti M,Ghe C,Cassoni P,et al.Growth hormone secretagogue binding sites in peripheral human tissues.J Clin Endocrinol Metab,2000(85):3803-3807
[37]Kojima M,Hosoda H,Kangawa K.Purification and distribution of ghrelin:the natural endogenous ligand for the growth hormone secretagogue receptor.Horm Res,2001(56):93-97
[38]Aart JV,Matthias TP,Mark LH,et al.Biological,Physiological,Pathophysiological,and Pharmacological Aspects of Ghrelin.Endocrine Reviews,2004;25(3):426-457
[39]Tschop M,Smiley DL,Heiman ML.Ghrelin induces adiposity in rodents.Nature,2000(407):908-913
[40]Wren AM,Small CJ,Ward HL,et al.The novel hypothalamic peptide ghrelin stimulates food intake and growth hormone secretion.Endocrinology,2000(141):4325-4328
[41]Nakazato M,Murakami N,Date Y,et al.A role for ghrelin in the central regulation of feeding.Nature,2001(409):194-198
[42]Wren AM,Seal LJ,Cohen MA,et al.Ghrelin enhances appetite and increases food intake in humans.J Clin Endocrinol Metab,2001 (86):5992-5995
[43]F Tassone,F Broglio,S Destefanis,et al.Neuroendocrine and Metabolic Effects of Acute Ghrelin Administration in Human Obesity.J Clin Endocrinol Metab,2003;88(11):5478-5483
[44]Neary NM,Small CJ,Wren AM,et al.Ghrelin Increases Energy Intake in Cancer Patients with Impaired Appetite:Acute,Randomized,Placebo-Controlled Trial.J Clin Endocrinol Metab,2004(89):2832-2836
[45]Wortley KE,Anderson KD,Garcia K,et al.Genetic deletion of ghrelin does not decrease food intake but influences metabolic fuel preference.Proc Natl Acad Sci USA,2004;101(21):8227-8232
[46]Kichoon Choi,Sang-Gun Roh,Yeon-Hee Hong,et al.The Role of Ghrelin and Growth Hormone Secretagogues Receptor on Rat Adipogenesis.Endocrinology,2003;144(3):754-759
[47]Min Seon Kim,Cho Ya Yoon,Pil Geum Jang,et al.The Mitogenic and Antiapoptotic Actions of Ghrelin in 3T3-L1 Adipocytes.Molecular Endocrinology,2004;18 (9):2291-2301
[48]Zhang W,Lili Zhao,Theodore R.et al.Inhibition of Adipogenesis by Ghrelin.Molecular Biology of the Cell,2004(15):2484-2491
[49]Ott V,Fasshauer M,Dalski A,et al.Direct peripheral effects of ghrelin include suppression of adiponectin expression.Horm Metab Res,2002(34):640-645
[50]St-Pierre DH,Karelis AD,St-Onge M,et al.Relationship between ghrelin and energy expenditure in healthy young women.J Clin Endocrinol Metab,2004;89(12):5993-5997
[51]Marzullo P,Verti B,Savia G,et al.The relationship between active ghrelin levels and human obesity involves alterations in resting energy expenditure.J Clin Endocrinol Metab,2004(89):936-939
[52]RⅡs AL,Hansen TK,Moller N,et al.Hyperthyroidism is associated with suppressed circulating ghrelin levels.J Clin Endocrinol Metab,2003(88):853-857
[53]Fukuda H,Mizuta Y,Isomoto H,et al.Ghrelin enhance gastric motility through direct stimulation of intrinsic neural pathways and capsaicin-sensitive afferent neurons in rats.Scand J Gastroenterol,2004;39(12):1209-1214
[54]Tang-Christensen M,Vrang N,Ortmann S,et al.Central administration of ghrelin and agouti-related protein(83-132)increase food intake and decreases spontaneous locomotor activeity in rats.Endocrinology,2004;145(10):4645-4652
[55]Matsumura K,Tsuchihashi T,FujⅡ K,et al.Central Ghrelin Modulates Sympathetic Activity in Conscious Rabbits.Hypertension,2002(40):694-699
[56]Catherine BL,Amelie CS,Florence MHB,et al.Acute Central Ghrelin and GH Secretagogues Induce Feeding and Activate Brain Appetite Centers.Endocrinology,2002(143):155-162
[57]Cummings DE,Foster-Schubert KE,OverduinJ.Ghrelin and Energy Balance:Focus on Current Controversies.Current Drug Targets,2005(6):153-169
[58]Wren AM,Small CJ,Abbott CR,et al.Ghrelin causes hyperphagia and obesity in rats.Diabetes,2001(50):2540-2547
[59]Date Y,Murakami N,Toshinai K,et al.The role of the gastric afferent vagal nerve in ghrelin induced feeding and growth hormone secretion in rats.Gastroenterology,2002;123(4):1120-1128.
[60]Cowley MA,Smith RG,Diano S,et al.The Distribution and Mechanism of Action of Ghrelin in the CNS Demonstrates a Novel Hypothalamic Circuit.Regulating Energy Homeostasis.Neuron,2003 (37):649-661
[61]Guan JL,Wang QP,Kageyama H,et al.Synaptic interactions between ghrelin-and neuropeptide Y-containing neurons in the rat arcuate nucleus.Peptides,2003(24):1921-1928
[62]Hu Z,Cha SH,Van Haasteren G,et al.Effect of centrally administered C75,a fatty acid synthase inhibitor,on ghrelin secretion and its downstream effects.Proc Natl Acad Sci USA,2005;102(11):3972-3977
[63]Asakawa A,Inui A,Kaga T,et al.Antagonism of ghrelin recaptor reduces food intake and body weght gain in mice.Gut,2003;52(7):947-952
[64]Tolle V,Bassant MH,Zizzari P,et al.Ultradian rhythmicity of ghrelin secretion in relation with GH,feeding behavior,and sleep-wake patterns in rats.Endocrinology,2002(143):1353-1361
[65]Tschop M,Wawarta R,Riepl RL,et al.Post-prandial decrease of circulating human ghrelin levels.J Endocrinol Invest,2001(24):19-21
[66]Cummings DE,Weigle DS,Frayo RS,et al.Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery.N Engl J Med,2002(346):1623-1630
[67]Blom WA,Stafleu A,de Graaf C,et al.Ghrelin response to carbohydrate enriched breakfast is related to insulin.Am J Clin Nutr,2005;81(2):367-375
[68]Mohlig M,Spranger J,Otto B,et al.Euglycemic hyperinsulinemia,but not lipid infusion,decreases circulating ghrelin levels in humans.J Endocrinol Invest,2002(25):36-38
[69]Dall R,Kanaley J,Hansen TK,et al.Plasma ghrelin levels during exercise in healthy subjects and in growth hormone-deficient patients.Eur J Endocrinol,2002(147):65-70
[70]Kallio J,Pensonen U,Karvonen MK,et al.Enhanced Exercise-Induced GH Secretion in Subjects with Pro7 Substitution in the Prepro-NPY.J Clin Endocrinol Metab,2001;86(11):5348-5352
[71]Schmidt A,Maier C,Schaller G,et al.Acute exercise has no effect on ghrelin plasma concentrations.Horm Metab Res,2004(36):174-177
[72]Zoladz J A,Konturek SJ.Effect of moderate incremental exercise,performed in fed and fasted state on cardio-respiratory variables and leptin and ghrelin concentrations in young healthy men.Physiol Pharmacol,2005;56(l):63-85
[73]RR Kraemer,RJ Durand,EO Acevedo,et al.Rigorous running increases growth hormone and insulin-like growth factor-1 without altering ghrelin.Exp Biol Med,(Maywood.) 2004(229):240-246
[74]Takano H,Morita T,lida H,et al.Hemodynamic and hormonal responses to a short-term low-intensity resistance exercise with the reduction of muscle blood flow.Eur J Appl Physiol,2005;95(l):65-73
[75]Andersson U,Treebak JT,Nielsen JN,et al.Exercise in rats does not alter hypothalamic AMP-activated protein kinase activity.Biochem Biophys Res Commun,2005 (2):719-725
[76]Karen E.Foster-Schubert,Anne McTiernan,et al.Human Plasma Ghrelin Levels Increase during a One-Year Exercise Program.J Clin Endocrinol Metab,2005(90):2820-2825
[77]Garcia JM,Iyer D,Poston WS,et al.Rise of plasma ghrelin with weight loss is not sustained during weight maintenance.Obesity(Silver Spring).,2006;14(10):1716-1723
[78]Hyun Kwak,Hyun Jun Kim,Sangyeoup Lee,et al.The Effects of Combined Exercise on Adiponectin and Acyl-Ghrelin in Overweight and Obese Elementary School Boys.Archives of Physical Medicine and Rehabilitation,2006(11):e40
[79]KJ Mackelvie,GS Meneilly,D Elahi,et al.Regulation of Appetite in Lean and Obese Adolescents Following Exercise:Role of Acylated and Desacyl ghrelin.J Clin Endocrin Metab,First published ahead of print November 21,2006 as doi:10.1210/jc.2006-1028
[80]De Souza MJ,Hontscharuk R,Olmsted M,et al.Drive for thinness score is a proxy indicator of energy deficiency in exercising women.Appetite,(2007),doi:10.1016/j.appet.2006.10.009
[81]Abbass Ghanbari-Niaki.Ghrelin and glucoregulatory hormone responses to a single circuit resistance exercise in male college students.Clinical Biochemistry,2006 (39):966-970
[82]Kraemer RR,Durand RJ,Hollander DB,et al.Ghrelin and other glucoregulatory hormone responses to eccentric and concentric muscle contractions.Endocrine,2004;24(l):93-98
[83]Jurimae J,Hofmann P,Jurimae T,et al.Plasma ghrelin responses to acute sculling exercises in elite male rowers.Eur J Appl Physiol.,2007;99(5):467-474
[84]Christ ER,Zehnder M,Boesch C,et al.The effect of increased lipid intake on hormonal responses during aerobic exercise in endurance trained men.Eur J Endocrinol,2006(154):397-403
[85]McK.ee KK,Tan CP,Palyha OC,et al.Cloning and characterization of two human G protein-coupled receptor genes (GPR38 and GPR39) related to the growth hormone secretagogue and neurotensin receptors.Genomics,1997;46(3):426-434
[86]Broglio F,Prodam F,Riganti F,et al.Ghrelin:from somatotrope secretion to new perspectives in the regulation of peripheral metabolic functions.Frontiers of Hormone Research,2006(35):102-114
[87]Gualillo O,Lago F,Casanueva FF,et al.One ancestor,several peptides Post-transiational modifications of preproghrelin generate several peptides with antithetical effects.Molecular and Cellular Endocrinology,2006(256):1-8
[88]Siok L Dun,G Cristina Brailoiu,Eugen Brailoiu,et al.Distribution and biological activity of obestatin in the rat.Journal of Endocrinology,2006 (191):481-489
[89]Bresciani E,Rapetti D,Dona F,et al.Obestatin inhibits feeding but does not modulate GH and corticosterone secretion in the rat.J Endocrinol Invest,2006(29):16-18
[90]Moechars D,Depoortere I,Moreaux B,et al.Altered gastrointestinal and metabolic function in the GPR39-obestatin receptor-knockout mouse.Gastroenterology,2006(131):1131-1141
[91]Seoane LM,Al-Massadi O,Pazos Y,et al.Central obestatin administration does not modify either spontaneous or ghrelin-induced food intake in rats.J Endocrinol Invest,2006(29):13-15
[92]Bassil AK,Haglund Y,Brown J,et al.Little or no ability of obestatin to interact with ghrelin or modify motility in the rat gastrointestinal tract.Br J Pharmacol,2007(l 50):58-64
[93]G Gourcerol,M Million,DW Adelson,et al.Lack of interaction between peripheral injection of CCK and obestatin in the regulation of gastric satiety signaling in rodents.Peptides,2006(27):2811-2819
[94]Rube'n Nogueiras,Paul Pfluger,Sulay Tovar,et al.Effects of Obestatin on Energy Balance and Growth Hormone Secretion in Rodents.Endocrinology,2007;148(l):21-26
[95]de Smet B,Thijs T,Peeters TL,et al.Effect of peripheral obestatin on gastric emptying and intestinal contractility in rodents.Neurogastroenterol Motil.,2007;19(3):211-217
[96]Sibilia V,Bresciani E,Lattuada N,et al.lntracerebroventricular acute and chronic administration of obestatin minimally affect food intake but not weight gain in the rat.J Endocrinol Invest,2006;29(ll):31-34
[97]Jackson VR,Nothacker HP,Civelli O.GPR39 receptor expression in the mouse brain.Neuroreport,2006(17):813-816
[98]Hoist B,Egerod KL,Schild E,et al.GPR39 Signaling Is Stimulated by Zinc Ions But Not by Obestatin.Endocrinology,2007(148):13-20
[99]Erwin L,Bart L,Lutgarde A,et al.Obestatin does not activate orphan G protein-coupled receptor GPR39.Biochem Biophys Res Commun,(2006),doi:10.1016/j.bbrc.2006.09.141
[100]N Chartrel,RA Perez,J Leprince,et al.Comment on“Obestatin,a Peptide Encoded by the Ghrelin Gene,Opposes Ghrelin's Effects on Food Intake”.Science,2007(315):766c
[101]Pan W,Tu H,Kastin AJ.Differential BBB interactions of three ingestive peptides:Obestatin,ghrelin,and adiponectin.Peptides,2006(27):911-916
[102]Szentirmai E,Krueger JM.Obestatin alters sleep in rats.Neurosci Lett,2006(404):222-226
[103]Tatemoto K,Carlquist M,Mutt V.Neuropeptide Y—a novel brain peptide with structural similarities to peptide YY and pancreatic polypeptide.Nature,1982(296):659-660
[104]Dan Larhammar.Evolution of neuropeptide Y,peptide YY and pancreatic polypeptide.Regulatory Peptides,1996(l):l-ll
[105]Blundell TL,Pitts JE,Tickle IJ,et al.X-ray analysis (1.4 A resolution) of avian pancreatic polypeptide:small globular protein hormone.Proc Natl Acad Sci USA,1981(78):4175—4179
[106]Fuhlendorff J,Langeland Johansen N,Melberg SG,et al.The antiparallel pancreatic polypeptide fold in the binding of neuropeptide Y to Yl and Y2 receptors.J Biol Chem,1990 (265):11706-11712
[107]Cerda-Reverter JM,Larhammar D.Neuropeptide Y family of peptides:structure,anatomical expression,function,and molecular evolution.Biochem Cell Biol,2000(78):371-392
[108]Chronwall BM,Dimaggio DA,Massari VJ,et al.The anatomy of neuropeptide Y-containing neurons in the rat brain.Neuroscience,1985(15):1159-1181
[109]DiMaggio DA,Chronwall BM,Buchman K,et al.Pancreatic polypeptide immunoreactivity in rat brain is actually neuropeptide Y.Neuroscience,1985(15):1149-1157
[110]Heilig M,Widerlov E.Neurobiology and clinical aspects of neuropeptide Y.Crit Rev Neurobiol,1995(9):115-136
[111]Liposits ZS,Sievers L,Paull WK.Neuropeptide-Yand ACTH-immunoreactive innervation of corticotropin releasing factor (CRF)-synthesizing neurons in the hypothalamus of the rat.An immunocytochemical analysis at the light and electron microscopic levels.Histochemistry,1988(88):227-234
[112]Cavadas C,Ribeiro CA,Cotrim M,et al.Catecholamine and neuropeptide Y secretion from human adrenal chromaffin cells:effect of nicotine and KC1.Ann NY Acad Sci,2002(971):332-334
[113]BM Chronwall,DA DiMaggio,VJ Massari,et al.The anatomy of neuropeptide-Y-containing neurons in rat brain.Neuroscience,1985 (15):1159-1181
[114]Dumont Y,Martel JC,Fouruier A,et al.Neuropeptide Y and neuropeptide Y receptor subtypes in brain and peripheral tissues.Prog Neurobiol,1992(38):125-167
[115]Blomqvist AG,Herzog H.Y-receptor subtypes—how many more?Trends Neurosci, 1997(20):294-298
[116]Berglund MM,Hipskind PA,Gehlert DR.Recent developments in our understanding of the physiological role of PP-fold peptide receptorsubtypes.Exp Biol Med,2003(228):217-244
[117]Fetissov SO,Kopp J,Hokfelt T.Distribution of NPY receptors in the hypothalamus.Neuropeptides,2004;38(4):175-188
[118]D.R.Gehlert.Introduction to the reviews on neuropeptide Y.Neuropeptides,2004;38(4):135-140
[119]Gehlert,DR.Subtypes of receptors for neuropeptide Y:Implications for the targeting of therapeutics.Life Sci,1994 (55):551-562
[120]JT Clark,PS Kalra,WR Crowley,et al.Neuropeptide Y and human pancreatic polypeptide stimulate feeding behavior in rats.Endocrinology,1984(115):427-429
[121]Morley JE,Levine AS,Gosnell BA,et al.Effect of neuropeptide Y on ingestive behaviors in the rat.Am J Physiol,1987(252):599-609
[122]Stanley BG,Anderson KC,Grayson MH,et al.Repeated hypothalamic stimulation with neuropeptide Y increases daily carbohydrate and fat intake and body weight gain in female rats.Physiol Behav,1989(46):173-177
[123]Leibowitz SF,Alexander JT.Analysis of neuropeptide Y-induced feeding:dissociation of Yl and Y2 receptor effects on natural meal patterns.Peptides,1991 (12):1251—1260
[124]Grove KL,Chen P,Koegler FH,et al.Fasting activates neuropeptide Y neurons in the arcuate and the paraventricular nucleus in the rhesus macaque.Mol Brain Res,2003(113):133-138
[125]Calza' L,Giardino L,Battistini N,et al.Increase of neuropeptide Y-like immunoreactivity in the paraventricular nucleus of fasting rats.Neurosci Lett,1989(104):99-104
[126]Xu B,Kalra PS,Moldawer LL,et al.Increased appetite augments hypothalamic NPY Yl receptor gene expression:effects of anorexigenic ciliary neurotropic factor.Regul Pept,1998 (75-76):391-395
[127]McMinn JE,Seeley RJ,Wilkinson SW,et al.NPY-induced overfeeding suppresses hypothalamic NPY mRNA expression:potential roles of plasma insulin and leptin.Regul Pept,1998(75-76):425^131
[128]Zarjevski N,Cusin I,Vettor R,et al.Chronic intracerebroventricular neuropeptide-Y administration to normal rats mimics hormonal and metabolic changes of obesity.Endocrinology,1993(133):1753-1758
[129]Stanley BG,Daniel DR,Chin AS,et al.Paraventricular injections of peptide YY and neuropeptide Y preferentially enhance carbohydrate ingestion.Peptides,1985(6):1205-1211
[130]CJ Billington,JE Briggs,M Grace,et al.Effects of intracerebroventricular injection of neuropeptide Y on energy metabolism.Am J Physiol,1991 (260):321-327
[131]M Szekely,E Petervari,E Pakai,et al.Acute,subacute and chronic effects of central neuropeptide Y on energy balance in rats.Neuropeptides,2005;39(2):103-115
[132]DE Lewis,L Shellard,DG Koeslag,et al.Intense exercise and food restriction cause similar hypothalamic neuropeptide Y increases in rats,Am J Physiol,1993(264):279-284
[133]Levin BE,Dunn-Meynell AA.Chronic exercise lowers the defended body weight gain and adiposity in diet-induced obese rats.Am J Physiol Regul Integr Comp Physiol.,2004;286(4):771-778
[134]Karamouzis I,Karamouzis M,Vrabas IS,et al.The effects of marathon swimming on serum leptin and plasma neuropeptide Y levels.Clin Chem Lab Med.,2002;40(2):132-136
[135]Chen JX,Zhao X,Yue GX,et al.Influence of Acute and Chronic Treadmill Exercise on Rat Plasma Lactate and Brain NPy,L-ENK,DYN A(1-13).Cell Mol Neurobiol.,2007;27(1):1-10
[136]Bjornebekk A,Mathe AA,Brene S.Running has differential effects on NPY,opiates,and cell proliferation in an animal model of depression and controls.Neuropsychopharmacology.,2006;31(2):256-264
[137]CH Stenstr(o|¨)m,H Alexanderson,I Lundberg,et al.Exercise and variations in neuropeptide concentrations in rheumatoid arthritis.Neuropeptides,1999;33(4):260-264
[138]Bucinskaite V,Lundeberg T,Stenfors C,et al.Effects of electro-acupuncture and physical exercise on regional concentrations of neuropeptides in rat brain.Brain Res,1994;12(666):128-132
[139]Mal-Soon Shin,Hong Kim,Hyun-Kyung Chang,et al.Treadmill exercise suppresses diabetes-induced increment of neuropeptide Y expression in the hypothalamus of rats.Neuroscience Letters,2003(346):157-160
[140]刘庆春,刘晌烨,杜金赞等.短期内建立营养性肥胖动物模型的实验研究.Medical journal of the People's Armed Police Forces,2004;15(5):371-372
[141]孙坚,张中成,刘至诚.营养性肥胖动物模型的实验研究.中国药理学通报,2002;18(4):466-467
[142]余上斌,刘声远,刘垒等.营养性肥胖大鼠血浆肾上腺髓质素水平变化.中国公共卫生,2005;21(10):1219-1220
[143]杨爱君,崔雁,叶卉初等.营养性肥胖动物模型的建立.临床和实验医学杂志,2005;4(3):156-157
[144]Zhi-Fu Guo,Xing Zheng,Yong-Wen Qin,et al.Circulating Preprandial Ghrelin to Obestatin Ratio Is Increased in Human Obesity.J Clin Endocrin Metab,First published ahead of print February 13,2007 as doi:10.1210/jc.2006-2306
[145]Zahorska MB,Obuchowicz E,Waluga M,et al.Neuropeptide Y in obese women during treatment with adrenergic modulation drugs.Med Sci Monit.,2001;7(3):403-408
[146]Lou XM,Duan GC,Chen J,et al.Blood leptin,orexins and NPY levels and their relations in obese children.Sichuan Da Xue Xue Bao Yi Xue Ban.,2006;37(4):621-624
[147]Hansen M J,Jovanovska V,Morris MJ.Adaptive responses in hypothalamic neuropeptide Y in the face of prolonged high-fat feeding in the rat.J Neurochem,2004(88):909-916
[148]Michael GD,Satya PK,Pushpa SK.Low abundance of NPY in the hypothalamus can produce hyperphagia and obesity.Peptides,2007(28):475-479
[149]H Chen,Michelle JH,Jessica EJ.Regulation of hypothalamic NPY by diet and smoking.Peptides,2007(28):384-389
[2]Melanie S.Moorel,Caroline J.Dodd,Joanne R.Welsman,et al.Short-term appetite and energy intake following imposed exercise in 9-to 10-year-old girls.Appetite,2004(43):127-134
[3]Maraki F,Tsofliou YP,Pitsiladis,et al.Acute effects of a single exercise class on appetite,energy intake and mood.Is there a time of day effect?Appetite,2005(45):272-278
[4]Hubert P,King NA,Blundell JE.Uncoupling the effects of energy expenditure and energy intake:Appetite response to short-term energy deficit induced by meal omission and physical activity.Appetite,1998(31):9-19
[5]Thompson DA,Wolfe LA,Eikelboom R,et al.Acute effects of exercise intensity on appetite in young men.Med Sci Sports Exerc,1988,20(3):222-227
[6]Stubbs RJ,Sepp A,Hughes DA,et al.The effect of graded levels of exercise on energy intake and balance in free-living women.International Journal of Obesity,2002(26):866-869
[7]King NA,Burley VJ,Blundell JE.Exercise-induced suppression of appetite:Effects on food intake and implications for energy balance.Eur.J Clin Nutr,1994 (48):715-724
[8]King NA,Blundell JE.High-fat foods overcome the energy expenditure induced by high-intensity cycling or running.European Journal of Clinical Nutrition,1995 (49):114-123
[9]Westerterp MS,Verwegen CR,Ijedema MJ,et al.Acute effects of exercise or sauna on appetite in obese and nonobese men.Physiology and Behavior,1997 (62):1345-1354
[10]Harry RK,FXavier PS,Karen S,et al.Acute effects of exercise on food intake in obese and nonobese women.Am J Clin Nuir,1990(52):240-245
[11]George,VA,Morganstein A.Effect of moderate intensity exercise on acute enrgy intake in normal and overweight females.Appetite,2003 (40):43—46
[12]Pomerleau M,Imbeault P,Parker T.Effects of exercise intensity on food intake and appetite in women.Am J Clin Nutr,2004;80(5):1230-1236
[13]Woo R,Garrow JS,Pi-Sunyer FX.Effect of exercise on spontaneous calorie intake in obesity.Am J Clin Nutr,1982;36(3):470-477
[14]Westerterp KR,Saris WHM,Van EM,et al.Use of doubly labelled water technique in humans during heavy sustained exercise.J Appl Physiol,1986(61):2162-2167
[15]Verger P,Lanteaume MT,Louis-Sylvestre J.Human intake and choice of foods at intervals after exercise.Appetite,1992(18):93-99
[16]Verger P,Lanteaume MT,Louis-Sylvestre J.Free food choice after acute exercise in men.Appetite,1994(22):159-164
[17]Donnelly JE,Jacobsen DJ,Heelan KS,et al.The effects of 18 months of intermittent vs.continuous exercise on aerobic capacity,body weight and composition,and metabolic fitness in previously sedentary,moderately obese females.Int J Obes Relat Metab Disord,2000;24(5):566-572
[18]Donnelly JE,Kirk EP,Jacobsen DJ,et al.Effects of 16 mo of verified,supervised aerobic exercise on macronutrient intake in overweight men and women:the Midwest exercise trial.Am J Clin Nutr,2003;78(5):950-956
[19]Katarina Melzera,Bengt Kayserb,Wim HM Saris,et al.Effects of physical activity on food intake.Clinical Nutrition,2005;24(6):885-895
[20]Stubbs RJ,Hughes DA,Johnstone AM,et al.A decrease in physical activity affects appetite,energy,and nutrient balance in lean men feeding ad libitum,Am J Clin Nutr.2004;79(l):62-69
[21]Murgatroyd PR,Goldberg GR,Leahy FE,et al.Effects of inactivity and diet composition on human energy balance.Int J Obes Relat Metab Disord,1999;23(12):1269-1275
[22]Blundell JE,King NA.Physical activity and regulation of food intake:current evidence.Med Sci Sports Exerc,1999;31(ll):573-583
[23]Blundell JE,King NA.Exercise,appetite control,and energy balance,Nutrition.2000 (16):519-522
[24]Schwartz MW,Woods SC,Seeley RJ,et al.Is the energy homeostasis system inherently biased toward weight gain?Diabetes,2003(52):232-238
[25]Stephen C.Woods,Randy J.Seeley.Adiposity Signals and the Control of Homeostasis.Nutrition,2000;16(10):894-902
[26]George A.Bray.A Concise Review on the Therapeutics of Obesity Nutrition,2000(16):953-960
[27]Zhang JV,Ren PG,Avsian-Kretchmer O,et al.Obestatin,a peptide encoded by the ghrelin gene,opposes ghrelin's effects on food intake.Science,2005;310(5750):996-999
[28]Christopher G.Bell,Andrew J.Walley,Philippe Froguel.The genetics of human obesity.Nature Review,2005,3:221-234
[29]Kojima M,Hosoda H,Date Y,et al.Ghrelin is a growth-hormone-releasing acylated peptide from stomach.Nature,1999;402(6762):656-660
[30]Hosda H,Kojima M,Matasuo H,et al.Ghrelin and desacyl ghrelin:two major forms of rat ghrelin peptide in gastrointestinal tissue.Biochem Biophys Res Commun,2000;279(3):909-913
[31]Date Y,Kojima M,Hosoda H,et al.Ghrelin,a novel growth hormone-releasing acylated peptide,is synthesized in a distinct endocrine cell type in the gastrointestinal tracts of rats and humans.Endocrinology,2000(141):4255-4261
[32]Muccioli G,Tschop M,Papotti M,et al.Neuroendocrine and peripheral activities of ghrelin:implications in metabolism and obesity.Eur J Pharmacol,2002(440):235-254
[33]Howard AD,Feighner SD,Cully DF,et al.A receptor in pituitary and hypothalamus that functions in growth hormone release.Science,1996(273):974-977
[34]Gnanapavan S,Kola B,Bustin SA,et al.The tissue distribution of the mRNA of ghrelin and subtypes of its receptor,GHS-R,in humans.J Clin Endocrinol Metab,2002(87):2988-2991
[35]Muccioli G,Ghe C,Ghigo MC,et al.Specific receptors for synthetic GH secretagogues in the human brain and pituitary gland.J Endocrinol,1998(157):99—106
[36]Papotti M,Ghe C,Cassoni P,et al.Growth hormone secretagogue binding sites in peripheral human tissues.J Clin Endocrinol Metab,2000(85):3803-3807
[37]Kojima M,Hosoda H,Kangawa K.Purification and distribution of ghrelin:the natural endogenous ligand for the growth hormone secretagogue receptor.Horm Res,2001(56):93-97
[38]Aart JV,Matthias TP,Mark LH,et al.Biological,Physiological,Pathophysiological,and Pharmacological Aspects of Ghrelin.Endocrine Reviews,2004;25(3):426-457
[39]Tschop M,Smiley DL,Heiman ML.Ghrelin induces adiposity in rodents.Nature,2000(407):908-913
[40]Wren AM,Small CJ,Ward HL,et al.The novel hypothalamic peptide ghrelin stimulates food intake and growth hormone secretion.Endocrinology,2000(141):4325-4328
[41]Nakazato M,Murakami N,Date Y,et al.A role for ghrelin in the central regulation of feeding.Nature,2001(409):194-198
[42]Wren AM,Seal LJ,Cohen MA,et al.Ghrelin enhances appetite and increases food intake in humans.J Clin Endocrinol Metab,2001 (86):5992-5995
[43]F Tassone,F Broglio,S Destefanis,et al.Neuroendocrine and Metabolic Effects of Acute Ghrelin Administration in Human Obesity.J Clin Endocrinol Metab,2003;88(11):5478-5483
[44]Neary NM,Small CJ,Wren AM,et al.Ghrelin Increases Energy Intake in Cancer Patients with Impaired Appetite:Acute,Randomized,Placebo-Controlled Trial.J Clin Endocrinol Metab,2004(89):2832-2836
[45]Wortley KE,Anderson KD,Garcia K,et al.Genetic deletion of ghrelin does not decrease food intake but influences metabolic fuel preference.Proc Natl Acad Sci USA,2004;101(21):8227-8232
[46]Kichoon Choi,Sang-Gun Roh,Yeon-Hee Hong,et al.The Role of Ghrelin and Growth Hormone Secretagogues Receptor on Rat Adipogenesis.Endocrinology,2003;144(3):754-759
[47]Min Seon Kim,Cho Ya Yoon,Pil Geum Jang,et al.The Mitogenic and Antiapoptotic Actions of Ghrelin in 3T3-L1 Adipocytes.Molecular Endocrinology,2004;18 (9):2291-2301
[48]Zhang W,Lili Zhao,Theodore R.et al.Inhibition of Adipogenesis by Ghrelin.Molecular Biology of the Cell,2004(15):2484-2491
[49]Ott V,Fasshauer M,Dalski A,et al.Direct peripheral effects of ghrelin include suppression of adiponectin expression.Horm Metab Res,2002(34):640-645
[50]St-Pierre DH,Karelis AD,St-Onge M,et al.Relationship between ghrelin and energy expenditure in healthy young women.J Clin Endocrinol Metab,2004;89(12):5993-5997
[51]Marzullo P,Verti B,Savia G,et al.The relationship between active ghrelin levels and human obesity involves alterations in resting energy expenditure.J Clin Endocrinol Metab,2004(89):936-939
[52]RⅡs AL,Hansen TK,Moller N,et al.Hyperthyroidism is associated with suppressed circulating ghrelin levels.J Clin Endocrinol Metab,2003(88):853-857
[53]Fukuda H,Mizuta Y,Isomoto H,et al.Ghrelin enhance gastric motility through direct stimulation of intrinsic neural pathways and capsaicin-sensitive afferent neurons in rats.Scand J Gastroenterol,2004;39(12):1209-1214
[54]Tang-Christensen M,Vrang N,Ortmann S,et al.Central administration of ghrelin and agouti-related protein(83-132)increase food intake and decreases spontaneous locomotor activeity in rats.Endocrinology,2004;145(10):4645-4652
[55]Matsumura K,Tsuchihashi T,FujⅡ K,et al.Central Ghrelin Modulates Sympathetic Activity in Conscious Rabbits.Hypertension,2002(40):694-699
[56]Catherine BL,Amelie CS,Florence MHB,et al.Acute Central Ghrelin and GH Secretagogues Induce Feeding and Activate Brain Appetite Centers.Endocrinology,2002(143):155-162
[57]Cummings DE,Foster-Schubert KE,OverduinJ.Ghrelin and Energy Balance:Focus on Current Controversies.Current Drug Targets,2005(6):153-169
[58]Wren AM,Small CJ,Abbott CR,et al.Ghrelin causes hyperphagia and obesity in rats.Diabetes,2001(50):2540-2547
[59]Date Y,Murakami N,Toshinai K,et al.The role of the gastric afferent vagal nerve in ghrelin induced feeding and growth hormone secretion in rats.Gastroenterology,2002;123(4):1120-1128.
[60]Cowley MA,Smith RG,Diano S,et al.The Distribution and Mechanism of Action of Ghrelin in the CNS Demonstrates a Novel Hypothalamic Circuit.Regulating Energy Homeostasis.Neuron,2003 (37):649-661
[61]Guan JL,Wang QP,Kageyama H,et al.Synaptic interactions between ghrelin-and neuropeptide Y-containing neurons in the rat arcuate nucleus.Peptides,2003(24):1921-1928
[62]Hu Z,Cha SH,Van Haasteren G,et al.Effect of centrally administered C75,a fatty acid synthase inhibitor,on ghrelin secretion and its downstream effects.Proc Natl Acad Sci USA,2005;102(11):3972-3977
[63]Asakawa A,Inui A,Kaga T,et al.Antagonism of ghrelin recaptor reduces food intake and body weght gain in mice.Gut,2003;52(7):947-952
[64]Tolle V,Bassant MH,Zizzari P,et al.Ultradian rhythmicity of ghrelin secretion in relation with GH,feeding behavior,and sleep-wake patterns in rats.Endocrinology,2002(143):1353-1361
[65]Tschop M,Wawarta R,Riepl RL,et al.Post-prandial decrease of circulating human ghrelin levels.J Endocrinol Invest,2001(24):19-21
[66]Cummings DE,Weigle DS,Frayo RS,et al.Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery.N Engl J Med,2002(346):1623-1630
[67]Blom WA,Stafleu A,de Graaf C,et al.Ghrelin response to carbohydrate enriched breakfast is related to insulin.Am J Clin Nutr,2005;81(2):367-375
[68]Mohlig M,Spranger J,Otto B,et al.Euglycemic hyperinsulinemia,but not lipid infusion,decreases circulating ghrelin levels in humans.J Endocrinol Invest,2002(25):36-38
[69]Dall R,Kanaley J,Hansen TK,et al.Plasma ghrelin levels during exercise in healthy subjects and in growth hormone-deficient patients.Eur J Endocrinol,2002(147):65-70
[70]Kallio J,Pensonen U,Karvonen MK,et al.Enhanced Exercise-Induced GH Secretion in Subjects with Pro7 Substitution in the Prepro-NPY.J Clin Endocrinol Metab,2001;86(11):5348-5352
[71]Schmidt A,Maier C,Schaller G,et al.Acute exercise has no effect on ghrelin plasma concentrations.Horm Metab Res,2004(36):174-177
[72]Zoladz J A,Konturek SJ.Effect of moderate incremental exercise,performed in fed and fasted state on cardio-respiratory variables and leptin and ghrelin concentrations in young healthy men.Physiol Pharmacol,2005;56(l):63-85
[73]RR Kraemer,RJ Durand,EO Acevedo,et al.Rigorous running increases growth hormone and insulin-like growth factor-1 without altering ghrelin.Exp Biol Med,(Maywood.) 2004(229):240-246
[74]Takano H,Morita T,lida H,et al.Hemodynamic and hormonal responses to a short-term low-intensity resistance exercise with the reduction of muscle blood flow.Eur J Appl Physiol,2005;95(l):65-73
[75]Andersson U,Treebak JT,Nielsen JN,et al.Exercise in rats does not alter hypothalamic AMP-activated protein kinase activity.Biochem Biophys Res Commun,2005 (2):719-725
[76]Karen E.Foster-Schubert,Anne McTiernan,et al.Human Plasma Ghrelin Levels Increase during a One-Year Exercise Program.J Clin Endocrinol Metab,2005(90):2820-2825
[77]Garcia JM,Iyer D,Poston WS,et al.Rise of plasma ghrelin with weight loss is not sustained during weight maintenance.Obesity(Silver Spring).,2006;14(10):1716-1723
[78]Hyun Kwak,Hyun Jun Kim,Sangyeoup Lee,et al.The Effects of Combined Exercise on Adiponectin and Acyl-Ghrelin in Overweight and Obese Elementary School Boys.Archives of Physical Medicine and Rehabilitation,2006(11):e40
[79]KJ Mackelvie,GS Meneilly,D Elahi,et al.Regulation of Appetite in Lean and Obese Adolescents Following Exercise:Role of Acylated and Desacyl ghrelin.J Clin Endocrin Metab,First published ahead of print November 21,2006 as doi:10.1210/jc.2006-1028
[80]De Souza MJ,Hontscharuk R,Olmsted M,et al.Drive for thinness score is a proxy indicator of energy deficiency in exercising women.Appetite,(2007),doi:10.1016/j.appet.2006.10.009
[81]Abbass Ghanbari-Niaki.Ghrelin and glucoregulatory hormone responses to a single circuit resistance exercise in male college students.Clinical Biochemistry,2006 (39):966-970
[82]Kraemer RR,Durand RJ,Hollander DB,et al.Ghrelin and other glucoregulatory hormone responses to eccentric and concentric muscle contractions.Endocrine,2004;24(l):93-98
[83]Jurimae J,Hofmann P,Jurimae T,et al.Plasma ghrelin responses to acute sculling exercises in elite male rowers.Eur J Appl Physiol.,2007;99(5):467-474
[84]Christ ER,Zehnder M,Boesch C,et al.The effect of increased lipid intake on hormonal responses during aerobic exercise in endurance trained men.Eur J Endocrinol,2006(154):397-403
[85]McK.ee KK,Tan CP,Palyha OC,et al.Cloning and characterization of two human G protein-coupled receptor genes (GPR38 and GPR39) related to the growth hormone secretagogue and neurotensin receptors.Genomics,1997;46(3):426-434
[86]Broglio F,Prodam F,Riganti F,et al.Ghrelin:from somatotrope secretion to new perspectives in the regulation of peripheral metabolic functions.Frontiers of Hormone Research,2006(35):102-114
[87]Gualillo O,Lago F,Casanueva FF,et al.One ancestor,several peptides Post-transiational modifications of preproghrelin generate several peptides with antithetical effects.Molecular and Cellular Endocrinology,2006(256):1-8
[88]Siok L Dun,G Cristina Brailoiu,Eugen Brailoiu,et al.Distribution and biological activity of obestatin in the rat.Journal of Endocrinology,2006 (191):481-489
[89]Bresciani E,Rapetti D,Dona F,et al.Obestatin inhibits feeding but does not modulate GH and corticosterone secretion in the rat.J Endocrinol Invest,2006(29):16-18
[90]Moechars D,Depoortere I,Moreaux B,et al.Altered gastrointestinal and metabolic function in the GPR39-obestatin receptor-knockout mouse.Gastroenterology,2006(131):1131-1141
[91]Seoane LM,Al-Massadi O,Pazos Y,et al.Central obestatin administration does not modify either spontaneous or ghrelin-induced food intake in rats.J Endocrinol Invest,2006(29):13-15
[92]Bassil AK,Haglund Y,Brown J,et al.Little or no ability of obestatin to interact with ghrelin or modify motility in the rat gastrointestinal tract.Br J Pharmacol,2007(l 50):58-64
[93]G Gourcerol,M Million,DW Adelson,et al.Lack of interaction between peripheral injection of CCK and obestatin in the regulation of gastric satiety signaling in rodents.Peptides,2006(27):2811-2819
[94]Rube'n Nogueiras,Paul Pfluger,Sulay Tovar,et al.Effects of Obestatin on Energy Balance and Growth Hormone Secretion in Rodents.Endocrinology,2007;148(l):21-26
[95]de Smet B,Thijs T,Peeters TL,et al.Effect of peripheral obestatin on gastric emptying and intestinal contractility in rodents.Neurogastroenterol Motil.,2007;19(3):211-217
[96]Sibilia V,Bresciani E,Lattuada N,et al.lntracerebroventricular acute and chronic administration of obestatin minimally affect food intake but not weight gain in the rat.J Endocrinol Invest,2006;29(ll):31-34
[97]Jackson VR,Nothacker HP,Civelli O.GPR39 receptor expression in the mouse brain.Neuroreport,2006(17):813-816
[98]Hoist B,Egerod KL,Schild E,et al.GPR39 Signaling Is Stimulated by Zinc Ions But Not by Obestatin.Endocrinology,2007(148):13-20
[99]Erwin L,Bart L,Lutgarde A,et al.Obestatin does not activate orphan G protein-coupled receptor GPR39.Biochem Biophys Res Commun,(2006),doi:10.1016/j.bbrc.2006.09.141
[100]N Chartrel,RA Perez,J Leprince,et al.Comment on“Obestatin,a Peptide Encoded by the Ghrelin Gene,Opposes Ghrelin's Effects on Food Intake”.Science,2007(315):766c
[101]Pan W,Tu H,Kastin AJ.Differential BBB interactions of three ingestive peptides:Obestatin,ghrelin,and adiponectin.Peptides,2006(27):911-916
[102]Szentirmai E,Krueger JM.Obestatin alters sleep in rats.Neurosci Lett,2006(404):222-226
[103]Tatemoto K,Carlquist M,Mutt V.Neuropeptide Y—a novel brain peptide with structural similarities to peptide YY and pancreatic polypeptide.Nature,1982(296):659-660
[104]Dan Larhammar.Evolution of neuropeptide Y,peptide YY and pancreatic polypeptide.Regulatory Peptides,1996(l):l-ll
[105]Blundell TL,Pitts JE,Tickle IJ,et al.X-ray analysis (1.4 A resolution) of avian pancreatic polypeptide:small globular protein hormone.Proc Natl Acad Sci USA,1981(78):4175—4179
[106]Fuhlendorff J,Langeland Johansen N,Melberg SG,et al.The antiparallel pancreatic polypeptide fold in the binding of neuropeptide Y to Yl and Y2 receptors.J Biol Chem,1990 (265):11706-11712
[107]Cerda-Reverter JM,Larhammar D.Neuropeptide Y family of peptides:structure,anatomical expression,function,and molecular evolution.Biochem Cell Biol,2000(78):371-392
[108]Chronwall BM,Dimaggio DA,Massari VJ,et al.The anatomy of neuropeptide Y-containing neurons in the rat brain.Neuroscience,1985(15):1159-1181
[109]DiMaggio DA,Chronwall BM,Buchman K,et al.Pancreatic polypeptide immunoreactivity in rat brain is actually neuropeptide Y.Neuroscience,1985(15):1149-1157
[110]Heilig M,Widerlov E.Neurobiology and clinical aspects of neuropeptide Y.Crit Rev Neurobiol,1995(9):115-136
[111]Liposits ZS,Sievers L,Paull WK.Neuropeptide-Yand ACTH-immunoreactive innervation of corticotropin releasing factor (CRF)-synthesizing neurons in the hypothalamus of the rat.An immunocytochemical analysis at the light and electron microscopic levels.Histochemistry,1988(88):227-234
[112]Cavadas C,Ribeiro CA,Cotrim M,et al.Catecholamine and neuropeptide Y secretion from human adrenal chromaffin cells:effect of nicotine and KC1.Ann NY Acad Sci,2002(971):332-334
[113]BM Chronwall,DA DiMaggio,VJ Massari,et al.The anatomy of neuropeptide-Y-containing neurons in rat brain.Neuroscience,1985 (15):1159-1181
[114]Dumont Y,Martel JC,Fouruier A,et al.Neuropeptide Y and neuropeptide Y receptor subtypes in brain and peripheral tissues.Prog Neurobiol,1992(38):125-167
[115]Blomqvist AG,Herzog H.Y-receptor subtypes—how many more?Trends Neurosci, 1997(20):294-298
[116]Berglund MM,Hipskind PA,Gehlert DR.Recent developments in our understanding of the physiological role of PP-fold peptide receptorsubtypes.Exp Biol Med,2003(228):217-244
[117]Fetissov SO,Kopp J,Hokfelt T.Distribution of NPY receptors in the hypothalamus.Neuropeptides,2004;38(4):175-188
[118]D.R.Gehlert.Introduction to the reviews on neuropeptide Y.Neuropeptides,2004;38(4):135-140
[119]Gehlert,DR.Subtypes of receptors for neuropeptide Y:Implications for the targeting of therapeutics.Life Sci,1994 (55):551-562
[120]JT Clark,PS Kalra,WR Crowley,et al.Neuropeptide Y and human pancreatic polypeptide stimulate feeding behavior in rats.Endocrinology,1984(115):427-429
[121]Morley JE,Levine AS,Gosnell BA,et al.Effect of neuropeptide Y on ingestive behaviors in the rat.Am J Physiol,1987(252):599-609
[122]Stanley BG,Anderson KC,Grayson MH,et al.Repeated hypothalamic stimulation with neuropeptide Y increases daily carbohydrate and fat intake and body weight gain in female rats.Physiol Behav,1989(46):173-177
[123]Leibowitz SF,Alexander JT.Analysis of neuropeptide Y-induced feeding:dissociation of Yl and Y2 receptor effects on natural meal patterns.Peptides,1991 (12):1251—1260
[124]Grove KL,Chen P,Koegler FH,et al.Fasting activates neuropeptide Y neurons in the arcuate and the paraventricular nucleus in the rhesus macaque.Mol Brain Res,2003(113):133-138
[125]Calza' L,Giardino L,Battistini N,et al.Increase of neuropeptide Y-like immunoreactivity in the paraventricular nucleus of fasting rats.Neurosci Lett,1989(104):99-104
[126]Xu B,Kalra PS,Moldawer LL,et al.Increased appetite augments hypothalamic NPY Yl receptor gene expression:effects of anorexigenic ciliary neurotropic factor.Regul Pept,1998 (75-76):391-395
[127]McMinn JE,Seeley RJ,Wilkinson SW,et al.NPY-induced overfeeding suppresses hypothalamic NPY mRNA expression:potential roles of plasma insulin and leptin.Regul Pept,1998(75-76):425^131
[128]Zarjevski N,Cusin I,Vettor R,et al.Chronic intracerebroventricular neuropeptide-Y administration to normal rats mimics hormonal and metabolic changes of obesity.Endocrinology,1993(133):1753-1758
[129]Stanley BG,Daniel DR,Chin AS,et al.Paraventricular injections of peptide YY and neuropeptide Y preferentially enhance carbohydrate ingestion.Peptides,1985(6):1205-1211
[130]CJ Billington,JE Briggs,M Grace,et al.Effects of intracerebroventricular injection of neuropeptide Y on energy metabolism.Am J Physiol,1991 (260):321-327
[131]M Szekely,E Petervari,E Pakai,et al.Acute,subacute and chronic effects of central neuropeptide Y on energy balance in rats.Neuropeptides,2005;39(2):103-115
[132]DE Lewis,L Shellard,DG Koeslag,et al.Intense exercise and food restriction cause similar hypothalamic neuropeptide Y increases in rats,Am J Physiol,1993(264):279-284
[133]Levin BE,Dunn-Meynell AA.Chronic exercise lowers the defended body weight gain and adiposity in diet-induced obese rats.Am J Physiol Regul Integr Comp Physiol.,2004;286(4):771-778
[134]Karamouzis I,Karamouzis M,Vrabas IS,et al.The effects of marathon swimming on serum leptin and plasma neuropeptide Y levels.Clin Chem Lab Med.,2002;40(2):132-136
[135]Chen JX,Zhao X,Yue GX,et al.Influence of Acute and Chronic Treadmill Exercise on Rat Plasma Lactate and Brain NPy,L-ENK,DYN A(1-13).Cell Mol Neurobiol.,2007;27(1):1-10
[136]Bjornebekk A,Mathe AA,Brene S.Running has differential effects on NPY,opiates,and cell proliferation in an animal model of depression and controls.Neuropsychopharmacology.,2006;31(2):256-264
[137]CH Stenstr(o|¨)m,H Alexanderson,I Lundberg,et al.Exercise and variations in neuropeptide concentrations in rheumatoid arthritis.Neuropeptides,1999;33(4):260-264
[138]Bucinskaite V,Lundeberg T,Stenfors C,et al.Effects of electro-acupuncture and physical exercise on regional concentrations of neuropeptides in rat brain.Brain Res,1994;12(666):128-132
[139]Mal-Soon Shin,Hong Kim,Hyun-Kyung Chang,et al.Treadmill exercise suppresses diabetes-induced increment of neuropeptide Y expression in the hypothalamus of rats.Neuroscience Letters,2003(346):157-160
[140]刘庆春,刘晌烨,杜金赞等.短期内建立营养性肥胖动物模型的实验研究.Medical journal of the People's Armed Police Forces,2004;15(5):371-372
[141]孙坚,张中成,刘至诚.营养性肥胖动物模型的实验研究.中国药理学通报,2002;18(4):466-467
[142]余上斌,刘声远,刘垒等.营养性肥胖大鼠血浆肾上腺髓质素水平变化.中国公共卫生,2005;21(10):1219-1220
[143]杨爱君,崔雁,叶卉初等.营养性肥胖动物模型的建立.临床和实验医学杂志,2005;4(3):156-157
[144]Zhi-Fu Guo,Xing Zheng,Yong-Wen Qin,et al.Circulating Preprandial Ghrelin to Obestatin Ratio Is Increased in Human Obesity.J Clin Endocrin Metab,First published ahead of print February 13,2007 as doi:10.1210/jc.2006-2306
[145]Zahorska MB,Obuchowicz E,Waluga M,et al.Neuropeptide Y in obese women during treatment with adrenergic modulation drugs.Med Sci Monit.,2001;7(3):403-408
[146]Lou XM,Duan GC,Chen J,et al.Blood leptin,orexins and NPY levels and their relations in obese children.Sichuan Da Xue Xue Bao Yi Xue Ban.,2006;37(4):621-624
[147]Hansen M J,Jovanovska V,Morris MJ.Adaptive responses in hypothalamic neuropeptide Y in the face of prolonged high-fat feeding in the rat.J Neurochem,2004(88):909-916
[148]Michael GD,Satya PK,Pushpa SK.Low abundance of NPY in the hypothalamus can produce hyperphagia and obesity.Peptides,2007(28):475-479
[149]H Chen,Michelle JH,Jessica EJ.Regulation of hypothalamic NPY by diet and smoking.Peptides,2007(28):384-389