脑-肠轴及其在动物摄食调控中的作用

doi:10.11843/j.issn.0366-6964.2015.07.001

摘要/Abstract

摘要：

摄食是动物的一种反射性活动，动物摄食行为的调节与脑-肠轴密切相关。动物摄食后，营养物质接触胃肠道从而刺激脑肠肽的释放，通过迷走传入神经元将信号传递给中枢神经系统，神经中枢将信号整合后经传出神经到达效应器官以促进或抑制摄食。脑-肠肽是参与食物摄取的重要的胃肠激素，在脑-肠轴调控摄食行为中起关键的作用，本文就脑-肠轴参与摄食调节作用方面的研究进展作一综述。

关键词: 脑-肠轴, 摄食调节, 脑-肠肽, ghrelin, NPY, orexin, CCK, GLP-1

Abstract:

Feeding is a reflective activity in animals，and regulation of feeding behavior is associated with brain-gut axis.After feeding，brain-gut peptides were released from gastrointestinal after receiving signal stimuli of nutrients，vagal afferent neurons received signal of brain-gut peptides and transferred them to central nervous system，which integrated these signals to effector organ and promoted or inhibited feeding.Brain-gut peptides，important gastrointestinal hormones involved in food intake，are playing a critical role in the regulation of feeding behavior of brain-gut axis.The advances on food intake regulation of brain-gut axis are reviewed in this article.

Key words: brain-gut axis, feeding regulation, brain-gut peptides, ghrelin, NPY, orexin, CCK, GLP-1

中图分类号:

S852

刘飞飞，秦贵信，姜海龙，孙泽威. 脑-肠轴及其在动物摄食调控中的作用[J]. 畜牧兽医学报, 2015, 46(7): 1077-1083.

LIU Fei-fei，QIN Gui-xin，JIANG Hai-long，SUN Ze-wei. Advanced of Brain-gut Axis and Its Role in Modulating Food Intake of Animals[J]. ACTA VETERINARIA ET ZOOTECHNICA SINICA, 2015, 46(7): 1077-1083.

参考文献

［1］WHITLOCK G，LEWINGTON S，SHERLIKER P，et al.Body-mass index and cause-specific mortality in 900 000 adults：collaborative analyses of 57 prospective studies［J］.Lancet，2009，373(9669)：1083-1096.
［2］ZHENG W，MCLERRAN D F，ROLLAND B，et al.Association between body-mass index and risk of death in more than 1 million Asians［J］.N Engl J Med，2011，364(8)：719-729.
［3］BREEN D M，YANG C S，LAM T K T.Gut-brain signalling：how lipids can trigger the gut［J］.Diabetes Metab Res Rev， 2011，27(2)：113-119.
［4］MITHIEUX G.Crosstalk between gastrointestinal neurons and the brain in the control of food intake［J］.Best Pract Res CL EN，2014，28：739-744.
［5］JANSSEN P，VANDEN BERGHE P，VERSCHUEREN S，et al.Review article：the role of gastric motility in the control of food intake［J］. Aliment Pharmacol Ther，2011，33(8)：880-894.
［6］CUMMINGS D E，OVERDUIN J.Gastrointestinal regulation of food intake［J］.Clin Invest，2007，117(1)：13-23.
［7］LAM C K L，CHARI M，RUTTER G A，et al.Hypothalamic nutrient sensing activates a forebrain–hindbrain neuronal circuit to regulate glucose production in vivo［J］. Diabetes，2011，60(1)：107-113.
［8］MORTON G J，CUMMINGS D E，BASKIN D G，et al.Central nervous system control of food intake and body weight［J］.Nature，2006，443(7109)：289-295.
［9］CHAUDHRI O B，FIELD B C T，BLOOM S R.Gastrointestinal satiety signals［J］.Int J Obes，2008，32：S28-S31.
［10］VERHULST P J，DEPOORTERE I.Ghrelin’s second life：from appetite stimulator to glucose regulator［J］.World J Gastroenterol，2012，18(25)：3183-3195.
［11］VITARRI F，DI GIANCAMILLO A，DEPONTI D，et al.Distribution of ghrelin-producing cells in the gastrointestinal tract of pigs at different ages［J］.Vet Res Commun，2012，36(1)：71-80.
［12］于高水，张文龙，黄勇，等.Ghrelin在撒能奶山羊胃肠道内的分布与表达［C］//兽医病理学会议［A］.2012：141.
YU G S，ZHANG W L，HUANG Y，et al.Distribution and expression of ghrelin in gastrointestinal tract of goats［C］//Veterinary Pathology Conference Proceedings［A］.2012：141.(in Chinese)
［13］BEWICK G A，KENT A，CAMPBELL D，et al.Mice with hyperghrelinemia are hyperphagic and glucose intolerant and have reduced leptin sensitivity［J］. Diabetes，2009，58(4)：840-846.
［14］KANG K S，YAHASHI S，MATSUDA K.Central and peripheral effects of ghrelin on energy balance，food intake and lipid metabolism in teleost fish［J］.Peptides，2011，32(11)：2242-2247.
［15］KATARZYNA K，DOROTA A Z.Ghrelin-mediated appetite regulation in the central nervous system［J］.Peptides，2011，32(11)：2256-2264.
［16］ZHANG H W，YIN J D，LI D F，et al.Tryptophan enhances ghrelin expression and secretion associated with increased food intake and weight gain in weanling pigs［J］.Domest Anim Endocrinol，2007，33(1)：47-61.
［17］SALFEN B E，CARROLL J A，KEISLER D H，et al.Effects of exogenous ghrelin on feed intake，weight gain，behavior，and endocrine responses in weanling pigs［J］.Anim Sci，2004，82(7)：1957-1966.
［18］TINOCO A B，NASLUND J，DELGADO M J，et al.Ghrelin increases food intake，swimming activity and growth in juvenile brown trout (Salmo trutta)［J］.Physiol Behav，2014，124：15-22.
［19］PAGE A J，SLATTERY J A，MILTE C，et al.Ghrelin selectively reduces mechanosensitivity of upper gastrointestinal vagal afferents［J］.Am J Physiol Gastrointest Liver Physiol，2007，292(5)：G1376-G1384.
［20］HOLZER P，REICHMANN F，FARZI A.Neuropeptide Y，peptide YY and pancreatic polypeptide in the gut-brain axis［J］.Neuropeptides，2012，46(6)：261-274.
［21］ZHANG L，BIJKER M S，HERZOG H，et al.The neuropeptide Y system：Pathophysiological and therapeutic implications in obesity and cancer［J］.Pharmacol Ther，2011，131(1)：91-113.
［22］PATEL D，PATEL N M.Review of NPY and NPY receptor for obesity［J］.Int J Pharm，2009，8：2.
［23］NGUYEN M V，JORDAL A E O，ESPE M，et al.Feed intake and brain neuropeptide Y (NPY) and cholecystokinin (CCK) gene expression in juvenile cobia fed plant-based protein diets with different lysine to arginine ratios［J］.Comp Biochem Phys A，2013，165 (3)：328-337.
［24］YOKOBORI E，AZUMA M，NISHIGUCHI R，et al.Neuropeptide Y stimulates food intake in the Zebrafish，Danio rerio［J］.J Neuroendocrinol，2012，24(5)：766-773.
［25］LUQUET S，PEREZ F A，HNASKO T S，et al.NPY/AgRP neurons are essential for feeding in adult mice but can be ablated in neonates［J］.Science，2005，310(5748)：683-685.
［26］MERCER R，CHEE M J S，COLMERS W F，et al.The role of NPY in hypothalamic mediated food intake［J］.Front Neuroendocrin，2011，32(4)：398-415.
［27］ZHOU Y，LIANG X F，YUAN X C，et al.Neuropeptide Y stimulates food intake and regulates metabolism in grass carp，Ctenopharyngodon idellus［J］.Aquaculture，2013，380：52-61.
［28］FILBY A L，PAULL G C，BARTLETT E J，et al.Physiological and health consequences of social status in zebrafish (Danio rerio)［J］.Physiol Behav，2010，101(5)：576-587.
［29］KAMIJO M，KOJIMA K，MARUYAMA K，et al.Neuropeptide Y in tiger puffer (Takifugu rubripes)：distribution，cloning，characterization and mRNA expression responses to prandial condition［J］.Zoolog Sci，2011，28(12)：882-890.
［30］MATSUDA K，KANG K S，SAKASHITA A，et al.Behavioral effectof neuropeptides related to feeding regulation in fish［J］.Ann N Y Acad Sci，2011，1220(1)：117-126.
［31］WONG K K Y，NG S Y L，LEE L T O，et al.Orexins and their receptors from fish to mammals：A comparative approach［J］.Gene Comp Endocrinol，2011，171(2)：124-130.
［32］SHIMIZU S，NAKAMACHI T，KONNO N，et al.Orexin A enhances food intake in bullfrog larvae［J］.Peptides，2014，59：79-82.
［33］DALL’AGLIO C，ZANNONI A，FORNI M，et al.Orexin system expression in the gastrointestinal tract of pigs［J］.Res Vet Sci，2013，95 (1)：8-14.
［34］DALL’AGLIO C，ZANNONI A，FORNI M，et al.Differential gene expression and immune localization of the orexin system in the major salivary glands of pigs［J］.Regul Pept，2011，172(1-3)：51-57.
［35］DALL’AGLIO C，PASCUCCI L，MERCATI F，et al.Identification of orexin A- and orexin type 2 receptor-positive cells in the gastrointestinal tract of neonatal dogs［J］. Eur J Histochem，2009，52(4)：229-236.
［36］DALL’AGLIO C，PASCUCCI L，MERCATI F，et al.Immunohistochemical identification and localization of orexin A and orexin type 2 receptor in the horse gastrointestinal tract［J］.Res Vet Sci，2009，86(2)：189-193.
［37］DALL’AGLIO C，PASCUCCI L，MERCATI F，et al.Localization of the orexin system in the gastrointestinal tract of fallow deer［J］.Acta Histochem，2012，114(2)：74-78.
［38］PENNEY C C，VOLKOFF H.Peripheral injections of cholecystokinin，apelin，ghrelin and orexin in cavefish (Astyanax fasciatus mexicanus)：Effects on feeding and on the brain expression levels of tyrosine hydroxylase，mechanistic target of rapamycin and appetite-related hormones［J］.Gen Comp Endocrinol，2014，196：34-40.
［39］YOKOBORI E，KOJIMA K，AZUMA M，et al.Stimulatory effect of intracerebroventricular administration of orexin A on foodintake in the zebrafish，Danio rerio［J］.Peptides，2011，32(7)：1357-1362.
［40］KIRSZ K，SZCZESNA M，DUDEK K，et al.Influence of season and nutritional status on the direct effects of leptin，orexin-A and ghrelin on luteinizing hormone and growth hormone secretion in the ovine pituitary explant model［J］.Domest Anim Endocrin，2014，48：69-76.
［41］王俊波，李艳君，宁树君，等.GLP-1-IR细胞在鼠、猪和人胎儿肠道的分布［J］.解剖科学进展，2000，6(2)：140-143.
WANG J B，LI Y J，NING S J，et al.Study of distribution on GLP-1-IR cells in the gut of rat，pig and foetus of human［J］.Progress Anatom Science，2000，6(2)：140-143.(in Chinese)
［42］HOLST J J.The physiology of glucagon-like peptide 1［J］.Physiol Rev，2007，87(4)：1409-1439.
［43］WILLIAMS D L.Neural integration of satiation and food reward：Role of GLP-1 and orexin pathways［J］. Physiol Behav，2014，136：194-199.
［44］PUNJABI M，ARNOLD M，GEARY N，et al.Peripheral glucagon-like peptide-1 (GLP-1) and satiation［J］.Physiol Behav，2011，105(1)：71-76.
［45］POLENI P E，AKIEDA-ASAI S，KODA S，et al.Possible involvement of melanocortin-4-receptor and AMP-activated protein kinase in the interaction of glucagon-like peptide-1 and leptin on feeding in rats［J］.Biochem Biophys Res Commun，2012，420(1)：36-41.
［46］PARKINSON J R C，CHAUDHRI O B，KUO Y T，et al.Differential patterns of neuronal activation in the brainstem and hypothalamus following peripheral injection of GLP-1，oxyntomodulin and lithium chloride in mice detected by manganese enhanced magnetic resonance imaging (MEMRI)［J］.Neuroimage，2009，44(3)：1022-1031.
［47］CHARLOTTE C R，GUILLAUME D L，HELEN E R.Ability of GLP-1 to decrease food intake is dependent on nutritional status［J］.Physiol Behav，2014，135：222-229.
［48］HAYES M R，KANOSKI S E，ALHADEFF A L，et al.Comparative effects of the long-acting GLP-1 receptor ligands，liraglutide and exendin-4，on food intake and body weight suppression in rats［J］.Obesity，2011，19(7)：1342-1349.
［49］PLAMBOECK A，VEEDFALD S，DEACON C F，et al.The effect of exogenous GLP-1 on food intake is lost in male truncally vagotomized subjects with pyloroplasty［J］.Am J Physiol Gastrointest Liver Physiol，2013，304(12)：1117-1127.
［50］SCHIRRA J，NICOLAUS M，WOERLE H，et al.GLP-1 regulates gastroduodenal motility involving cholinergic pathways［J］.Neurogastroent Motil，2009，21(6)：609-618.
［51］ABBOTT C R，MONTEIRO M，SMALL C J，et al.The inhibitory effects of peripheral administration of peptide YY(3-36) and glucagon-like peptide-1 on food intake are attenuated by ablation of the vagal-brainstem-hypothalamic pathway［J］.Brain Res，2005，1044(1)：127-131.
［52］LIDDLE R A.Cholecystokinin：its role in health and disease［J］.Curr Opin Endocrinol Diabetes，2003，10(1)：50-54.
［53］CHEUNG G W C，KOKOROVIC A，LAM C K L，et al.Intestinal cholecystokinin controls glucose production through a neuronal network［J］.Cell Metab，2009，10(2)：99-109.
［54］MORAN T H，KINZIG K P.Gastrointestinal satiety signals II.Cholecystokinin［J］.Am J Physiol Gastrointest Liver Physiol，2004，286 (2)：183-188.
［55］DOCKRAY G J.Cholecystokinin［J］.Curr Opin Endocrinol Diabetes Obes，2012，19：8-12.
［56］LIOU A P，LU X，SEI Y，et al.The G-protein-coupled receptor GPR40 directly mediates long-chain fatty acid-induced secretion of cholecystokinin［J］.Gastroenterology，2011，140(3)：903-912.
［57］SUOMINEN A H，GLIMM D R，OKINE E K，et al.Development of an in vivo method to study bovine intestinal response to dietary manipulation at the molecular level［J］.J Anim Sci，1998，76(10)：2678-2686.
［58］RIPKEN D，VAN DER WIELEN N，VAN DER MEULEN J，et al.Cholecystokinin regulates satiation independently of the abdominal vagal nerve in a pig model of total subdiaphragmatic vagotomy［J］.Physiol Behav，2015，139：167-176.
［59］谭岳华，黄生强.CCK、CCKAR 对动物采食量影响的研究进展［J］.猪与禽，2008，28（5）：69-71.
TAN Y H，HUANG S Q.Advances on the effect of CCK，CCKAR on the animal feed intake［J］.Pig Poultry，2008，28(5)：69-71.(in Chinese)
［60］ASADULLAH H P，MIYUKI I，MOTOKI S，et al.Immunohistochemical study on the ontogenetic development of the regional distribution of peptide YY，pancreatic polypeptide，and glucagon-like peptide 1 endocrine cells in bovine gastrointestinal tract［J］.Regul Pept，2012，175(1)：15-20.
［61］STADLBAUER U，WOODS S C，LANGHANS W，et al.PYY_3-36：Beyond food intake［J］.Front Neuroendocrin，2015，38：1-11.
［62］BABU M，PURHONEN A K，BANSIEWICZ T，et al.Effect of total colectomy and PYY infusion on food intake and body weight in rats［J］.Regul Pept，2005，131(1)：29-33.
［63］KOUKEI M，ATSUSHI S，ERI Y，et al.Neuroendocrine control of feeding behavior and psychomotor activity by neuropeptide Y in fish［J］.Neuropeptides，2012，46(6)：275-283.
［64］DE SILVA A，SALEM V，LONG C J，et al.The gut hormones PYY_3-36 and GLP-1_7-36 amide reduce food intake and modulate brain activity in appetite centers in humans［J］.Cell Metab，2011，14(5)：700-706.

[1]	蔡国栋, 孙凯, 项自来, 王玲, 邹辉, 顾建红, 袁燕, 刘学忠, 刘宗平, 卞建春. 玉米赤霉烯酮对小鼠T淋巴细胞体外活化、增殖的影响[J]. 畜牧兽医学报, 2017, 48(7): 1357-1364.
[2]	蔡国栋, 孙凯, 项自来, 王玲, 邹辉, 顾建红, 袁燕, 刘学忠, 刘宗平, 卞建春. 玉米赤霉烯酮对小鼠T淋巴细胞体外活化、增殖的影响[J]. 畜牧兽医学报, 2017, 48(7): 1357-1364.
[3]	沈向华, 潘登, 范奎奎, 李强, 李婷, 杜晨光. Ghrelin通过弓状核区域α型雌二醇受体神经元介导雌性小鼠采食调控[J]. 畜牧兽医学报, 2017, 48(12): 2399-2406.
[4]	沈向华, 潘登, 范奎奎, 李强, 李婷, 杜晨光. Ghrelin通过弓状核区域α型雌二醇受体神经元介导雌性小鼠采食调控[J]. 畜牧兽医学报, 2017, 48(12): 2399-2406.
[5]	刘骄，张曼，金鑫，范燕茹，田巧珍，杨银凤. 梅花鹿体内脑肠肽的表达及细胞定位分析[J]. 畜牧兽医学报, 2017, 48(1): 157-165.
[6]	刘骄，张曼，金鑫，范燕茹，田巧珍，杨银凤. 梅花鹿体内脑肠肽的表达及细胞定位分析[J]. 畜牧兽医学报, 2017, 48(1): 157-165.
[7]	贾知锋，王纯洁，敖日格乐，高瑞娟，巴森胡. 乳酸链球菌素对大肠杆菌所致腹泻小鼠的脑-肠轴中单胺类神经递质的影响[J]. 畜牧兽医学报, 2016, 47(9): 1931-1939.
[8]	贾知锋，王纯洁，敖日格乐，高瑞娟，巴森胡. 乳酸链球菌素对大肠杆菌所致腹泻小鼠的脑-肠轴中单胺类神经递质的影响[J]. 畜牧兽医学报, 2016, 47(9): 1931-1939.
[9]	张曼，金鑫，刘骄，杨银凤. Ghrelin在驯鹿器官内的表达及定位检测[J]. 畜牧兽医学报, 2016, 47(12): 2510-2519.
[10]	张曼，金鑫，刘骄，杨银凤. Ghrelin在驯鹿器官内的表达及定位检测[J]. 畜牧兽医学报, 2016, 47(12): 2510-2519.
[11]	刘飞飞，秦贵信，姜海龙，孙泽威. 脑-肠轴及其在动物摄食调控中的作用[J]. 畜牧兽医学报, 2015, 46(7): 1077-1083.
[12]	杨燕燕，青格勒，达来，张冠华，彭灿泉，邵凯，苏和，田瑛，王新奇，郭延华，乌达巴拉，周璇，曹贵方. Ghrelin对绵羊早期体外胚胎发育的影响[J]. 畜牧兽医学报, 2014, 45(6): 926-931.
[13]	杨燕燕，青格勒，达来，张冠华，彭灿泉，邵凯，苏和，田瑛，王新奇，郭延华，乌达巴拉，周璇，曹贵方. Ghrelin对绵羊早期体外胚胎发育的影响[J]. 畜牧兽医学报, 2014, 45(6): 926-931.
[14]	米焱，张伶俐，李海军，杜晨光，曹贵方，王秀梅. Ghrelin参与FSH对牛卵丘细胞体外增殖的调节[J]. 畜牧兽医学报, 2013, 44(8): 1236-1243.
[15]	米焱，张伶俐，李海军，杜晨光，曹贵方，王秀梅. Ghrelin参与FSH对牛卵丘细胞体外增殖的调节[J]. 畜牧兽医学报, 2013, 44(8): 1236-1243.