Nesfatin-1的分子生物学特征、功能及其基因表达的营养调控
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摘要
Nesfatin-1是由核组蛋白2(NUCB2)衍生而来的肽段,是一种由下丘脑和外周组织表达的厌食信号肽,通过使动物产生饱腹感而抑制动物摄食。研究者发现,Nesfatin-1除了通过抑制动物摄食调节机体内稳态与能量储备,还参与初情启动和胰岛素抵抗等多种生理过程,具有多种生物学功能,本文综述了Nesfatin-1/NUCB2的分子生物学特征、功能及其基因表达的营养调控。
Nesfatin-1 is a peptide fragment driven from nucleobindin 2( NUCB2) in hypothalamus and peripheral tissues,and inhibit animal feed intake by satiety. Researchers found that Nesfatin-1 not only modified the whole-body homeostasis and energy storage through inhibiting feed intake,but also played roles in many physiological processes such as regulating puberty onset and insulin resistance and so on,with a variety of biological functions. This article reviewed the molecular biological characteristics,functions and nutritional regulation in gene expression of Nesfatin-1 / NUCB2.
Nesfatin-1 is a peptide fragment driven from nucleobindin 2( NUCB2) in hypothalamus and peripheral tissues,and inhibit animal feed intake by satiety. Researchers found that Nesfatin-1 not only modified the whole-body homeostasis and energy storage through inhibiting feed intake,but also played roles in many physiological processes such as regulating puberty onset and insulin resistance and so on,with a variety of biological functions. This article reviewed the molecular biological characteristics,functions and nutritional regulation in gene expression of Nesfatin-1 / NUCB2.
引文
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[15]朱宇旌,丁兰,张勇,等.胰岛素对促性腺激素释放激素分泌及活性的调控[J].动物营养学报,2013,25(1):1-7.
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[19]STENGEL A,TACHéY.Nesfatin-1—role as possible new potent regulator of food intake[J].Regulatory Peptides,2010,163(1/2/3):18-23.
[20]GARCA-GALIANO D,NAVARRO V M,ROA J,et al.The anorexigenic neuropeptide,Nesfatin-1,is indispensable for norm al puberty onset in the fem ale rat[J].The Journal of Neuroscience,2010,30(23):7783-7792.
[21]MOHAN H,UNNIAPPAN S.Ontogenic pattern of nucleobindin-2/nesfatin-1 expression in the gastroenteropancreatic tissues and serum of Sprague Daw ley rats[J].Regulatory Peptides,2012,175(1/2/3):61-69.
[22]王尧尧,李冉,李运生,等.Nesfatin-1对初情期雌性大鼠促性腺激素及其mRNA表达的影响[J].中国农业大学学报,2015,20(3):139-145.
[23]张志红.下丘脑输注Nesfatin-1对肝脏AMPK/TORC2/AKT信号通路的影响[D].博士学位论文.重庆:重庆医科大学,2012.
[24]吴丹冬,杨刚毅,李钶,等.NUCB2 siRNA对肝细胞胰岛素信号通路及细胞凋亡的影响[J].免疫学杂志,2014(10):860-864.
[25]YANG M L,ZHANG Z H,WANG C,et al.Nesfatin-1 action in the brain increases insulin sensitivity through Akt/AM PK/TORC2 pathw ay in diet-induced insulin resistance[J].Diabetes,2012,61(8):1959-1968.
[26]WEISMAN R,COHEN A,GASSER S M.TORC2—a new player in genom e stability[J].EM BO M olecular M edicine,2014,6(8):995-1002.
[27]NAKATA M,MANAKA K,YAMAMOTO S,et al.Nesfatin-1 enhances glucose-induced insulin secretion by prom oting Ca2+influx through L-type channels in m ouse isletβ-cells[J].Endocrine Journal,2011,58(4):305-313.
[28]YOSTEN G L C,SAMSON W K.Nesfatin-1 exerts cardiovascular actions in brain:possible interaction w ith the central m elanocortin system[J].Am erican Journal of Physiology Regulatory,Integrative and Com parative Physiology,2009,297(2):R330-R336.
[29]MIMEE A,SMITH P M,FERGUSON A V.Nesfatin-1 influences the excitability of neurons in the nucleus of the solitary tract and regulates cardiovascular function[J].Am erican Journal of Physiology Regulatory,Integrative and Com parative Physiology,2012,302(11):R1297-R1304.
[30]KNCZL K,PINTR O,FERENCZI S,et al.Nesfatin-1 exerts long-term effect on food intake and body tem perature[J].International Journal of Obesity,2012,36(12):1514-1521.
[31]FOO K S,BRAUNER H,STENSON C G.Nucleobindin-2/nesfatin in the endocrine pancreas:distribution and relationship to glycaem ic state[J].Journal of Endocrinology,2010,204(3):255-263.
[32]GONZALEZ R,REINGOLD B K,GAO X D,et al.Nesfatin-1 exerts a direct,glucose-dependent insulinotropic action on m ouse isletβ-and M IN6 cells[J].Journal of Endocrinology,2011,208(3):R9-R16.
[33]MOHAN H,RAMESH N,MORTAZAVI S,et al.Nutrients differentially regulate nucleobindin-2/nesfatin-1in vitro in cultured stom ach ghrelinom a(M GN3-1)cells and in vivo in m ale m ice[J].PLo S One,2014,9(12):e11502.
[34]GONZALEZ R,PERRY R L S,GAO X,et al.Nutrient responsive nesfatin-1 regulates energy balance and induces glucose-stim ulated insulin secretion in rats[J].Endocrinology,2011,152(10):3628-3637.
[35]秦小云,王伯钧,伍善广,等.NUCB2/Nesfatin-1在DIO大鼠下丘脑中的表达[J].中国临床解剖学杂志,2014,32(6):704-707.
[36]吴博,刘重斌,董缪武,等.重复性饥饿/再投喂对大鼠下丘脑NUCB 2表达影响[J].中国公共卫生,2010,39(3):313-314.
[37]李清春,管洪在,陈曦,等.禁食前后小鼠胃黏膜NUCB 2的变化[J].青岛大学医学院学报,2010,46(3):206-208.
[38]HATEF A,SHAJAN S,UNNIAPPAN S.Nutrient status m odulates the expression of Nesfatin-1 encoding nucleobindin 2A and 2B m RNAs in zebrafish gut,liver and brain[J].General and Com parative Endocrinology,2014,215:51-60.
[39]SENIN L L,AL-MASSADI O,BARJA-FERNANDEZ S,et al.Regulation of NUCB2/Nesfatin-1 production in rat’s stom ach and adipose tissue is dependent on age,testosterone levels and lactating status[J].M olecular and Cellular Endocrinology,2015,411:105-112.
[40]BONNET M S,OUELAA W,TILLEMENT V,et al.Gastric distension activates NUCB2/nesfatin-1-expressing neurons in the nucleus of the solitary tract[J].Regulatory Peptides,2013,187:17-23.
[2]SHIMIZU H,OH-I S,HASHIMOTO K,et al.Peripheral adm inistration of nesfatin-1 reduces food intake in m ice:the leptin-independent m echanism[J].Endocrinology,2009,150(2):662-671.
[3]LENTS C A,BARB C R,HAUSMAN G J,et al.Effects of nesfatin-1 on food intake and LH secretion in prepubertal gilts and genom ic association of the porcine NUCB2 gene w ith grow th traits[J].Dom estic Anim al Endocrinology,2013,45(2):89-97.
[4]GAIGS,BONNET M S,TARDIVEL C,et al.c-Fos im m unoreactivity in the pig brain follow ing deoxynivalenol intoxication:focus on NUCB2/nesfatin-1 expressing neurons[J].Neuro Toxicology,2013,34:135-149.
[5]PALASZ A,KRYSTANEK M,WORTHINGTON J,et al.Nesfatin-1,a unique regulatory neuropeptide of the brain[J].Neuropeptides,2012,46(3):105-112.
[6]GONZALEZ R,SHEPPERD E,THIRUPPUGAZH V,et al.Nesfatin-1 regulates the hypothalam o-pituitary-ovarian axis of fish[J].Biology of Reproduction,2012,87(4):84.
[7]KOHNO D,NAKATA M,MAEJIMA Y,et al.Nesfatin-1 neurons in paraventricular and supraoptic nuclei of the rat hypothalam us coexpress oxytocin and vasopressin and are activated by refeeding[J].Endocrinology,2008,149(3):1295-1301.
[8]宋敏,田园,方富贵.Nesfatin-1与生殖[J].生理科学进展,2014,45(6):439-441.
[9]ZHANG A Q,LI X L,JIANG C Y,et al.Expression of nesfatin-1/NUCB2 in rodent digestive system[J].World Journal of Gastroenterology,2010,16(14):1735-1741.
[10]STENGEL A,GOEBEL M,YAKUBOV I,et al.Identification and characterization of nesfatin-1 im m unoreactivity in endocrine cell types of the rat gastric oxyntic m ucosa[J].Endocrinology,2009,150(1):232-238.
[11]GARCA-GALIANO D,PINEDA R,ILHAN T,et al.Cellular distribution,regulated expression,and functional role of the anorexigenic peptide,NUCB2/nesfatin-1,in the testis[J].Endocrinology,2012,153(4):1959-1971.
[12]FEIJO-BANDN S,RODRGUEZ-PENAS D,GARCA-RA V,et al.Nesfatin-1 in hum an and m urine cardiom yocytes:synthesis,secretion,and m obilization of GLUT-4[J].Endocrinology,2013,154(12):4757-4767.
[13]PAN W H,HSUCHOU H,KASTIN A J.Nesfatin-1crosses the blood-brain barrier w ithout saturation[J].Peptides,2007,28(11):2223-2228.
[14]FOO K S,BRISMAR H,BROBERGER C.Distribution and neuropeptide coexistence of nucleobindin-2m RNA/nesfatin-like im m unoreactivity in the rat CNS[J].Neuroscience,2008,156(3):563-579.
[15]朱宇旌,丁兰,张勇,等.胰岛素对促性腺激素释放激素分泌及活性的调控[J].动物营养学报,2013,25(1):1-7.
[16]VARRICCHIO E,RUSSOLILLO M G,RUSSO F,et al.Expression and im m unohistochem ical detection of Nesfatin-1 in the gastrointestinal tract of Casertana pig[J].Acta Histochemica,2014,116(4):583-587.
[17]GUO F F,XU L,GAO S L,et al.The effects of nesfatin-1 in the paraventricular nucleus on gastric m otility and its potential regulation by the lateral hypothalam ic area in rats[J].Journal of Neurochem istry,2015,132(3):266-275.
[18]王文杰,蒋正尧.nesfatin-1对大鼠迷走复合体内葡萄糖感受神经元和胃扩张敏感神经元兴奋性的作用[J].齐鲁医学杂志,2010,25(3):225-227.
[19]STENGEL A,TACHéY.Nesfatin-1—role as possible new potent regulator of food intake[J].Regulatory Peptides,2010,163(1/2/3):18-23.
[20]GARCA-GALIANO D,NAVARRO V M,ROA J,et al.The anorexigenic neuropeptide,Nesfatin-1,is indispensable for norm al puberty onset in the fem ale rat[J].The Journal of Neuroscience,2010,30(23):7783-7792.
[21]MOHAN H,UNNIAPPAN S.Ontogenic pattern of nucleobindin-2/nesfatin-1 expression in the gastroenteropancreatic tissues and serum of Sprague Daw ley rats[J].Regulatory Peptides,2012,175(1/2/3):61-69.
[22]王尧尧,李冉,李运生,等.Nesfatin-1对初情期雌性大鼠促性腺激素及其mRNA表达的影响[J].中国农业大学学报,2015,20(3):139-145.
[23]张志红.下丘脑输注Nesfatin-1对肝脏AMPK/TORC2/AKT信号通路的影响[D].博士学位论文.重庆:重庆医科大学,2012.
[24]吴丹冬,杨刚毅,李钶,等.NUCB2 siRNA对肝细胞胰岛素信号通路及细胞凋亡的影响[J].免疫学杂志,2014(10):860-864.
[25]YANG M L,ZHANG Z H,WANG C,et al.Nesfatin-1 action in the brain increases insulin sensitivity through Akt/AM PK/TORC2 pathw ay in diet-induced insulin resistance[J].Diabetes,2012,61(8):1959-1968.
[26]WEISMAN R,COHEN A,GASSER S M.TORC2—a new player in genom e stability[J].EM BO M olecular M edicine,2014,6(8):995-1002.
[27]NAKATA M,MANAKA K,YAMAMOTO S,et al.Nesfatin-1 enhances glucose-induced insulin secretion by prom oting Ca2+influx through L-type channels in m ouse isletβ-cells[J].Endocrine Journal,2011,58(4):305-313.
[28]YOSTEN G L C,SAMSON W K.Nesfatin-1 exerts cardiovascular actions in brain:possible interaction w ith the central m elanocortin system[J].Am erican Journal of Physiology Regulatory,Integrative and Com parative Physiology,2009,297(2):R330-R336.
[29]MIMEE A,SMITH P M,FERGUSON A V.Nesfatin-1 influences the excitability of neurons in the nucleus of the solitary tract and regulates cardiovascular function[J].Am erican Journal of Physiology Regulatory,Integrative and Com parative Physiology,2012,302(11):R1297-R1304.
[30]KNCZL K,PINTR O,FERENCZI S,et al.Nesfatin-1 exerts long-term effect on food intake and body tem perature[J].International Journal of Obesity,2012,36(12):1514-1521.
[31]FOO K S,BRAUNER H,STENSON C G.Nucleobindin-2/nesfatin in the endocrine pancreas:distribution and relationship to glycaem ic state[J].Journal of Endocrinology,2010,204(3):255-263.
[32]GONZALEZ R,REINGOLD B K,GAO X D,et al.Nesfatin-1 exerts a direct,glucose-dependent insulinotropic action on m ouse isletβ-and M IN6 cells[J].Journal of Endocrinology,2011,208(3):R9-R16.
[33]MOHAN H,RAMESH N,MORTAZAVI S,et al.Nutrients differentially regulate nucleobindin-2/nesfatin-1in vitro in cultured stom ach ghrelinom a(M GN3-1)cells and in vivo in m ale m ice[J].PLo S One,2014,9(12):e11502.
[34]GONZALEZ R,PERRY R L S,GAO X,et al.Nutrient responsive nesfatin-1 regulates energy balance and induces glucose-stim ulated insulin secretion in rats[J].Endocrinology,2011,152(10):3628-3637.
[35]秦小云,王伯钧,伍善广,等.NUCB2/Nesfatin-1在DIO大鼠下丘脑中的表达[J].中国临床解剖学杂志,2014,32(6):704-707.
[36]吴博,刘重斌,董缪武,等.重复性饥饿/再投喂对大鼠下丘脑NUCB 2表达影响[J].中国公共卫生,2010,39(3):313-314.
[37]李清春,管洪在,陈曦,等.禁食前后小鼠胃黏膜NUCB 2的变化[J].青岛大学医学院学报,2010,46(3):206-208.
[38]HATEF A,SHAJAN S,UNNIAPPAN S.Nutrient status m odulates the expression of Nesfatin-1 encoding nucleobindin 2A and 2B m RNAs in zebrafish gut,liver and brain[J].General and Com parative Endocrinology,2014,215:51-60.
[39]SENIN L L,AL-MASSADI O,BARJA-FERNANDEZ S,et al.Regulation of NUCB2/Nesfatin-1 production in rat’s stom ach and adipose tissue is dependent on age,testosterone levels and lactating status[J].M olecular and Cellular Endocrinology,2015,411:105-112.
[40]BONNET M S,OUELAA W,TILLEMENT V,et al.Gastric distension activates NUCB2/nesfatin-1-expressing neurons in the nucleus of the solitary tract[J].Regulatory Peptides,2013,187:17-23.