综述 Review

食欲素调控机体糖代谢

  • 王进宝 ,
  • 王建林 ,
  • 邵宝平
展开
  • 兰州大学生命科学学院动物研究所, 兰州 730000

收稿日期: 2013-05-08

  网络出版日期: 2013-10-27

基金资助

国家自然科学基金青年科学基金项目(31000190);中央高校基本科研业务费专项资金(860829)

Orexin: Regulation in Body Glucose Metabolism

  • WANG Jinbao ,
  • WANG Jianlin ,
  • SHAO Baoping
Expand
  • Institute of Zoology, School of Life Science, Lanzhou University, Lanzhou 730000, China

Received date: 2013-05-08

  Online published: 2013-10-27

摘要

下丘脑食欲素(orexin)是调节睡眠与觉醒、饮食行为、情感、自主神经活动以及全身糖代谢的主要神经肽之一。本文综述了下丘脑orexin在机体糖代谢平衡中的主要作用,阐述了orexin在糖代谢中的作用模式及其分子机制。

本文引用格式

王进宝 , 王建林 , 邵宝平 . 食欲素调控机体糖代谢[J]. 动物营养学报, 2013 , 25(11) : 2520 -2528 . DOI: 10.3969/j.issn.1006-267x.2013.11.003

Abstract

Hypothalamic orexin are known to regulate sleep/wake, feeding behavior, emotions, autonomic nerve activity, and whole-body glucose metabolism. This review mainly discussed the mian roles of orexin in glucose metabolism balance, and the action model and molecular mechanism in glucose metabolism.

参考文献

[1] SAKURAL T.The neural circuit of orexin (hypocretin):maintaining sleep and wakefulness[J].Nature Reviews Neuroscience,2007,8(3):171-181.

[2] DE LECEA L,KILDUFF T S,PEYRON C,et al.The hypocretins:hypothalamus-specific peptides with neuroexcitatory activity[J].Proceedings of the National Academy of Sciences of the United States of America,1998,95(1):322-327.  

[3] SAKURAL T,MIEDA M.Connectomics of orexin-producing neurons:interface of systems of emotion,energy homeostasis and arousal[J].Trends in Pharmacological Sciebces,2011,32(8):451-462.  

[4] WILLIE J T,TAKAHIRA H,SHIBAHARA M,et al.Ectopic overexpression of orexin alters sleep/wakefulness states and muscle tone regulation during REM sleep in mice[J].Journal of Molecular Neuroscience,2011,43(2):155-161.  

[5] TRIVEDI P,YU H,MACNEIL D J,et al.Distribution of orexin receptor mRNA in the rat brain[J].FEBS Letters,1998,438(1/2):71-75.

[6] MARCUS J N,ASCHKENASI C J,LEE C E,et al.Differential expression of orexin receptors 1 and 2 in the rat brain[J].The Journal of Comparative Neurology,2001,435(1):6-25.  

[7] 赵玉岩,郭磊,都健,等.增食欲素受体l在大鼠胰岛细胞中的表达研究[J].中国医科大学学报,2008,37(3):304-306.

[8] MORIGUCHI T,SAKURAI T,NAMBU T,et al.Neurons containing orexin in the lateral hypothalamic area of the adult rat brain are activated by insulin-induced acute hypoglycemia[J].Neuroscience Letters,1999,264(1/2/3):101-104.

[9] YAMANAKA A,BEUCKMANN C T,WILLIE J T,et al.Hypothalamic orexin neurons regulate arousal according to energy balance in mice[J].Neuron,2003,38(5):701-713.  

[10] BURDAKOV D,GERASIMENKO O,VERKHRATSKY A.Physiological changes in glucose differentially modulate the excitability of hypothalamic melanin-concentrating hormone and orexin neurons in situ[J].The Journal of Neuroscience,2005,25(9):2429-2433.  

[11] GRIFFOND B,RISOLD P Y,JACQUEMARD C,et al.Insulin-induced hypoglycemia increases preprohypocretin (orexin) mRNA in the rat lateral hypothalamic area[J].Neuroscience Letters,1999,262(2):77-80.  

[12] SCHULD A,HEBEBRAND J,GELLER F,et al.Increased body-mass index in patients with narcolepsy[J].Lancet,2000,355(9211):1274-1275.

[13] KOTZ C,NIXON J,BUTTERICK T,et al.Brain orexin promotes obesity resistance[J].Annals of the New York Academy of Sciences,2012,1264(1):72-86.  

[14] HARA J,BEUCKMANN CT,NAMBU T,et al.Genetic ablation of orexin neurons in mice results in narcolepsy,hypophagia,and obesity[J].Neuron,2001,30(2):345-354.  

[15] HARA J,YANAGISWA M,SAKURAI T.Difference in obesity phenotype between orexin-knockout mice and orexin neuron-deficient mice with same genetic background and environmental conditions[J].Neuroscience Letters,2005,380(3):239-242.  

[16] BURDAKOV D,ALEXOPOULOS H.Metabolic state signalling through central hypocretin/orexin neurons[J].Journal of Cellular and Molecular Medicine,2005,9(4):795-803.  

[17] GARCÍA-CÁCERES C,YI C X,TSCHOP M H.Hypothalamic astrocytes in obesity[J].Endocrinology and Metabolism Clinics of North America,2013,42(1):57-66.  

[18] MARINO J S,XU Y,HILL J W.Central insulin and leptin-mediated autonomic control of glucose homeostasis[J].Trends in Endocrinology and Metabolism,2011,22(7):275-285.

[19] KARNANI M,BURDAKOV D.Multiple hypothalamic circuits sense and regulate glucose levels[J].American Journal of Physiology:Regulatory,Integrative and Comparative Physiology,2011,300(1):R47-R55.

[20] TSUNEKI H,WADA T,SASAOKA T.Role of orexin in the regulation of glucose homeostasis[J].Acta Physiologica,2010,198(3):335-348.  

[21] BURDAKOV D,GONZÁLEZ J A.Physiological functions of glucose-inhibited neurones[J].Acta Physiologica,2009,195(1):71-78.  

[22] GONZALEZ J A,REIMANN F,BURDAKOV D.Dissociation between sensing and metabolism of glucose in sugar sensing neurones[J].Journal of Physiologica,2009,587(1):41-48.  

[23] BURDAKOV D,LUCKMAN S M,VERKHRATSKY A.Glucose-sensing neurons of the hypothalamus[J].Philosophical Transactions of the Royal Society of London:Series B,Biological Sciences,2005,360:2227-2235.

[24] GONZÁLEZ J A,JENSEN L T,FUGGER L,et al.Metabolism-independent sugar sensing in central orexin neurons[J].Diabetes,2008,57(10):2569-2576.  

[25] VENNER A,KARNANI M M,GONZALEZ J A,et al.Orexin neurons as conditional glucosensors:paradoxical regulation of sugar sensing by intracellular fuels[J].Journal of Physiology,2011,589(Pt 23):5701-5708.

[26] WILLIAMS R H,ALEXOPOULOS H,JENSEN L T,et al.Adaptive sugar sensors in hypothalamic feeding circuits[J].Proceedings of the National Academy of Sciences of the United States of America,2008,105(33):11975-11980.  

[27] FURUDONO Y,ANDO C,YAMAMOTO C,et al.Involvement of specific orexigenic neuropeptides in sweetener-induced overconsumption in rats[J].Behavioural Brain Research,2006,175(2):241-248.  

[28] BAIRD J P,CHOE A,LOVELAND J L,et al.Orexin-A hyperphagia:hindbrain participation in consummatory feeding responses[J].Endocrinology,2009,150(3):1202-1216.

[29] MATSUO E,MOCHIZUKI A,NAKAYAMA K,et al.Decreased intake of sucrose solutions in orexin knockout mice[J].Journal of Molecular Neuroscience,2011,43(2):217-224.  

[30] KARNANI M M,APERGS-SCHOUTE J,ADAMANTIDIS A,et al.Activation of central orexin/hypocretin neurons by dietary amino acids[J].Neuron,2011,72(4):616-629.  

[31] PEREZ-LEIGHTON C E,BUTTERCK-PETERSON T A,BILLINGGTON C J,et al.Role of orexin receptors in obesity:from cellular to behavioral evidence[J].International Journal of Obesity,2013,37(2):167-174.  

[32] YOSHIMICHI G,YOSHIMATSU H,MASAKI T,et al.Orexin-A regulates body temperature in coordination with arousal status[J].Experimental Biology and Medicine (Maywood),2001,226(5):468-476.

[33] CAI X J,EVANS M L,LISTER C A,et al.Hypoglycemia activates orexin neurons and selectively increases hypothalamic orexin-B levels:responses inhibited by feeding and possibly mediated by the nucleus of the solitary tract[J].Diabetes,2001,50(1):105-112.  

[34] OUEDRAOGO R,NASLUND E,KIRCHGESSNER A L.Glucose regulates the release of orexin-A from the endocrine pancreas[J].Diabetes,2003,52(1):111-117.  

[35] SAKURAI T.Roles of orexins in regulation of feeding and wakefulness[J].Neuroreport,2002,13(8):987-995.  

[36] MATSUMURA K,TSUCHIHASHI T,ABE I.Central orexin-a augments sympathoadrenal outflow in conscious rabbits[J].Hypertension,2001,37(6):1382-1387.  

[37] YI C X,SERLIE M J,ACKERMANS M T,et al.A major role for perifornical orexin neurons in the control of glucose metabolism in rats[J].Diabetes,2009,58(9):1998-2005.  

[38] TSUNEKI H,SUGIHARA Y,HONDA R,et al.Reduction of blood glucose level by orexins in fasting normal and streptozotocin-diabetic mice[J].European Journal of Pharmacology,2002,448(2/3):245-252.

[39] DUCROC R,VOISIN T,EL FIRAR A,et al.Orexins control intestinal glucose transport by distinct neuronal,endocrine,and direct epithelial pathways[J].Diabetes,2007,56(10):2494-2500.  

[40] INUI A.Transgenic approach to the study of body weight regulation[J].Pharmacological Reviews,2000,52(1):35-61.

[41] FUNATO H,TSAI A L,WILLIE J T,et al.Enhanced orexin receptor-2 signaling prevents diet-induced obesity and improves leptin sensitivity[J].Cell Metabolism,2009,9(1):64-76.  

[42] HAYNES A C,CHAPMAN H,TAYLOU C,et al.Anorectic,thermogenic and anti-obesity activity of a selective orexin-1 receptor antagonist in ob/ob mice[J].Regulatory Peptides,2002,104(1/2/3):153-159.

[43] SHUCHI T,HAPUE M S,OKAMOTO S,et al.Hypothalamic orexin stimulates feeding-associated glucose utilization in skeletal muscle via sympathetic nervous system[J].Cell Metabolism,2009,10(6):466-480.  

[44] RAMADORI G,FUJIKAWA T,ANDERSON J,et al.SIRT1 deacetylase in SF1 neurons protects against metabolic imbalance[J].Cell Metabolism,2011,14(3):301-312.  

[45] WILLIAMS T D,CHAMBERS J B,ROBERTS L M,et al.Diet-induced obesity and cardiovascular regulation in C57BL/6J mice[J].Clinical and Experimental Pharmacology and Physiology,2003,30(10):769-778.  

[46] TANNER J M,KEARNS D T,KIM B J,et al.Fasting-induced reductions in cardiovascular and metabolic variables occur sooner in obese versus lean mice[J].Experimental Biology and Medicine,2010,235(12):1489-1497.  

[47] CAI X J,WIDDOWSON P S,HARROLD J,et al.Hypothalamic orexin expression:modulation by blood glucose and feeding[J].Diabetes,1999,48(11):2132-2137.  

[48] GRIFFOND B,RISOLD P Y,JACQUEMARD C,et al.Insulin-induced hypoglycemia increases preprohypocretin(orexin)mRNA in the rat lateral hypothalamic area[J].Neuroscience Letters,1999,262(2):77-80.  

[49] TAKANO S,KANAI S,HOSOYA H,et al.Orexin-a does not stimulate food intake in old rats[J].American Journal of Physiology:Gastrointestinal and Liver Physiology,2004,287(6):1182-1187.  

[50] TSUNEKI H,MURATA S,ANZAWA Y,et al.Age-related insulin resistance in hypothalamus and peripheral tissues of orexin knockout mice[J].Diabetologia,2008,51(4):657-667.  

[51] YOSHIMATSU H,NIIJIMA A,OOMURA Y,et al.Lateral and ventromedial hypothalamic influences on hepatic autonomic nerve activity in the rat[J].Brain Research Bulletin,1988,21(2):239-244.  

[52] STANLEY S,PINTO S,SEGAL J,et al.Identification of neuronal subpopulations that project from hypothalamus to both liver and adipose tissue polysynaptically[J].Proceedings of the National Academy of Sciences of the United States of America,2010,107(15):7024-7029.  

[53] VAN DEN TOP M,NOLAN M F,LEE K,et al.Orexins induce increased excitability and synchronisation of rat sympathetic preganglionic neurones[J].Journal of Physiology,2003,549(3):809-821.  

[54] KALSBEEK A,YI C X,LA FLEUR S E,et al.The hypothalamic clock and its control of glucose homeostasis[J].Trends in Endocrinology and Metabolism,2010,21(7):402-410.  

[55] KALSBEEK A,SCHEER F A,PERREAU-LEBZ S,et al.Circadian disruption and SCN control of energy metabolism[J].FEBS Letters,2011,585(10):1412-1426.  

[56] PEYRON C,TIGHE D K,VAN DEN POL A N,et al.Neurons containing hypocretin(orexin)project to multiple neuronal systems[J].Journal of Neuroscience,1998,18(23):9996-10015.

[57] HARRISON T A,CHEN C T,DUN N J,et al.Hypothalamic orexin A-immunoreactive neurons project to the rat dorsal medulla[J].Neuroscience Letters,1999,273(1):17-20.  

[58] HWANG L L,CHEN C T,DUN N J.Mechanisms of orexin-induced depolarizations in rat dorsal motor nucleus of vagus neurones in vitro[J].Journal of Physiology,2001,537(2):511-520.  

[59] KREIER F,BUIJS R M.Evidence for parasympathetic innervation of white adipose tissue,clearing up some vagaries[J].American Journal of Physiology:Regulatory,Integrative and Comparative Physiology,2007,293(1):R548-R549.

[60] SHEN J,TANIDA M,YAO J F,et al.Biphasic effects of orexin-A on autonomic nerve activity and lipolysis[J].Neuroscience Letters,2008,444(24):166-171.

[61] TANIDA M,NIIJIMA A,SHEN J,et al.Dose-different effects of orexin-A on the renal sympathetic nerve and blood pressure in urethane-anesthetized rats[J].Experimental Biology and Medicine (Maywood),2006,231(10):1616-1625.

[62] SHIH C D,CHUANG Y C.Nitric oxide and GABA mediate bi-directional cardiovascular effects of orexin in the nucleus tractus solitarii of rats[J].Neuroscience,2007,149(3):625-635.  

[63] BASS J,TAKAHASHI J S.Circadian integration of metabolism and energetics[J].Science,2010,330:1349-1354.

[64] FROY O.Metabolism and circadian rhythms-implications for obesity[J].Endocrine Reviews,2010,31(1):1-24.  

[65] HUANG W Y,RAMSEY K M,MARCHEVA B,et al.Circadian rhythms,sleep,and metabolism[J].Journal of Clinical Investigation,2011,121(6):2133-2141.  

[66] YOSHIDA K,MCCORMACK S,ESPAR A,et al.Afferents to the orexin neurons of the rat brain[J].Journal of Comparative Neurology,2006,494(5):845-861.  

[67] ESTABROOKE I V,MCCARTHY M T,KO E,et al.Fos expression in orexin neurons varies with behavioral state[J].Journal of Neuroscience,2001,21(5):1656-1662.

[68] GOMPF H S,ASTON-JONES G.Role of orexin input in the diurnal rhythm of locus coeruleus impulse activity[J].Brain Research,2008,1224:43-52.

[69] TAHERI S,SUNTER D,DAKIN C,et al.Diurnal variation in orexin A immunoreactivity and prepro-orexin mRNA in the rat central nervous system[J].Neuroscience Letters,2000,279(2):109-112.  

[70] FUJIKI N,YOSHIDA Y,RIPLEY B,et al.Changes in CSF hypocretin-1 (orexin A) levels in rats across 24 hours and in response to food deprivation[J].Neuroreport,2001,12(5):993-997.  

[71] YOSHIDA Y,FUJIKI N,NAKAJIMA T,et al.Fluctuation of extracellular hypocretin-1 (orexin A) levels in the rat in relation to the light-dark cycle and sleep-wake activities[J].European Journal of Neuroscience,2001,14(7):1075-1081.  

[72] DESARNAUD F,MURILLO-RODRIGUEZ E,LIN L,et al.The diurnal rhythm of hypocretin in young and old F344 rats[J].Sleep,2004,27(5):851-856.

[73] HEINONEN M V,PURHONEN A K,MKEL K A,et al.Functions of orexins in peripheral tissues[J].Acta Physiologica,2008,192(4):471-485.  

[74] JÖHREN O,NEIDERT S J,KUMMER M,et al.Prepro-orexin and orexin receptor mRNAs are differentially expressed in peripheral tissues of male and female rats[J].Endocrinology,2001,142(8):3324-3331.  

[75] SKRZYPSKI M,LE T T,KACEMAREK P,et al.Orexin A stimulates glucose uptake,lipid accumulation and adiponectin secretion from 3T3-L1 adipocytes and isolated primary rat adipocytes[J].Diabetologia,2011,54(7):1841-1852.  

[76] BUTTERICK T A,NIXON J P,BILLINGTON C J,et al.Orexin A decreases lipid peroxidation and apoptosis in a novel hypothalamic cell model[J].Neuroscience Letters,2012,524(1):30-34.  

[77] SELLAYAH D,BHARAJ P,SIKDER D.Orexin is required for brown adipose tissue development,differentiation,and function[J].Cell Metabolism,2011,14(4):478-490.  

[78] LEINNINGER G M,OPLAND D M,JO Y H,et al.Leptin action via neurotensin neurons controls orexin,the mesolimbic dopamine system and energy balance[J].Cell Metabolism,2011,14(4):313-323.

[79] MUROYA S,FUNAHASHI H,YAMANAKA A,et al.Orexins (hypocretins) directly interact with neuropeptide Y,POMC and glucose-responsive neurons to regulate Ca2+ signaling in a reciprocal manner to leptin:orexigenic neuronal pathways in the mediobasal hypothalamus[J].European Journal of Neuroscience,2004,19(6):1524-1534.  

[80] SATOH A,BRACE C S,BEN-JOSEF G,et al.SIRT1 promotes the central adaptive response to diet restriction through activation of the dorsomedial and lateral nuclei of the hypothalamus[J].Journal of Neuroscience,2010,30(30):10220-10232.  

[81] SILVA J P,VON MEYENN F,HOWELL J,et al.Regulation of adaptive behaviour during fasting by hypothalamic Foxa2[J].Nature,2009,462:646-650.

[82] WILD S,ROGLiC G,GREEN A,et al.Global prevalence of diabetes:estimates for the year 2000 and projections for 2030[J].Diabetes Care,2004,27(5):1047-1053.  
文章导航

/