综述 Review

黑皮质素受体-4:生物学特征、作用机理和影响因素

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  • 沈阳农业大学畜牧兽医学院, 沈阳 110866
张鑫(1990—),女,河北张家口人,硕士研究生,从事动物营养与饲料科学研究。E-mail:15040043318@163.com

收稿日期: 2014-09-25

  网络出版日期: 2015-03-18

基金资助

国家自然科学基金(31101253;30973112)

Melanocortin-4 Receptor: Biological Characteristics, Mechanism and Influence Factors

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  • College of Veterinary and Animal Science, Shenyang Agricultural University, Shenyang 110866, China

Received date: 2014-09-25

  Online published: 2015-03-18

摘要

黑皮质素受体4(MC4R)是G-蛋白耦联受体(GPCR),是下丘脑分泌的一种肽类物质,在调控动物采食量中起着重要的作用。MC4R与阿黑皮质素原(POMC)分泌的α-促黑素(α-MSH)结合,激活下丘脑MC4R神经元的表达,从而抑制采食量。本文综述了MC4R的生物学特征及其在动物采食量调控中的作用机理,并阐述了影响MC4R活性的因素。

本文引用格式

张鑫, 李方方, 朱宇旌, 郑丽莉, 张勇 . 黑皮质素受体-4:生物学特征、作用机理和影响因素[J]. 动物营养学报, 2015 , 27(3) : 683 -690 . DOI: 10.3969/j.issn.1006-267x.2015.03.004

Abstract

The melanocortin-4 receptor (MC4R) is a typical G protein-coupled receptor (GPCR) which presents in the hypothalamus as a peptide, and plays an important role in feed intake regulation. It combines with α-melanocyte-stimulating hormone (α-MSH) which is secreted from pro-opiomelanocortin (POMC) and activates the expression of MC4R neuron to depress the feed intake of animals. The biological characteristics of MC4R and its mechanism in feed intake regulation were reviewed in the article.

参考文献

[1] TODOROVIC A,HASKELL-LUEVANO C.A review of melanocortin receptor small molecule ligands[J].Peptides,2005,26(10):2026-2036.  

[2] SRINIVASAN S,LUBRANO-BERTHELIER C,GOVAERTS C,et al.Constitutive activity of the melanocortin-4 receptor is maintained by its N-terminal domain and plays a role in energy homeostasis in humans[J].The Journal of Clinical Investigation,2004,114(8):1158-1164.  

[3] ADAN R A H,GISPEN W H.Brain melanocortin receptors:from cloning to function[J].Peptides,1997,18(8):1279-1287.  

[4] ABDEL-MALEK Z A.Melanocortin receptors:their functions and regulation by physiological agonists and antagonists[J].Cellular and Molecular Life Sciences,2001,58(3):434-441.  

[5] BREIT A,BVCH T R H,BOEKHOFF I,et al.Alternative G protein coupling and biased agonism:new insights into melanocortin-4 receptor signalling[J].Molecular and Cellular Endocrinology,2011,331(2):232-240.  

[6] YANG Y K.Structure,function and regulation of the melanocortin receptors[J].European Journal of Pharmacology,2011,660(1):125-130.  

[7] WEI R B,YUAN D Y,ZHOU C W,et al.Cloning,distribution and effects of fasting status of melanocortin 4 receptor (MC4R) in Schizothorax prenanti[J].Gene,2013,532(1):100-107.  

[8] KIM K S,LARSEN N,SHORT T,et al.A missense variant of the porcine melanocortin-4 receptor (MC4R) gene is associated with fatness,growth,and feed intake traits[J].Mammalian Genome,2000,11(2):131-135.  

[9] GANTZ I,MIWA H,KONDA Y,et al.Molecular cloning,expression,and gene localization of a fourth melanocortin receptor[J].The Journal of Biological Chemistry,1993,268(20):15174-15179.

[10] SWITONSKI M,MANKOWSKA M,SALAMON S.Family of melanocortin receptor (MCR) genes in mammals-mutations,polymorphisms and phenotypic effects[J].Journal of Applied Genetics,2013,54(4):461-472.  

[11] KIM K S,LARSEN N J,ROTHSCHILD M F.Rapid communication:linkage and physical mapping of the porcine melanocortin-4 receptor (MC4R) gene[J].Journal of Animal Science,2000,78(3):791-792.

[12] 聂茹,巴彩凤.黑皮质素受体-4调节通路的研究进展[J].中国实验动物学报,2008,16(4):317-320.

[13] ADAN R A H,TIESJEMA B,HILLEBRAND J J G,et al.The MC4 receptor and control of appetite[J].British Journal of Pharmacology,2006,149(7):815-827.  

[14] PALUCKI B L,PARK M K,NARGUND R P,et al.Discovery of (2S)-N-[(1R)-2- -1-piperidinyl]-1-[(4-fluorophenyl)methyl]-2-oxoethyl]-4-methyl-2-piperazinecarboxamide (MB243),a potent and selective melanocortin subtype-4 receptor agonist[J].Bioorganic & Medicinal Chemistry Letters,2005,15(1):171-175.  

[15] 张志岐,束刚,江青艳.下丘脑对脂类的营养感应及其参与食欲调控的机制[J].动物营养学报,2013,25(7):1395-1405.

[16] 郑溜丰,彭健.中枢神经系统整合外周信号调节采食量的分子机制[J].动物营养学报,2013,25(10):2212-2221.

[17] WYNNE K,STANLEY S,MCGOWAN B,et al.Appetite control[J].Journal of Endocrinology,2005,184(2):291-318.  

[18] 施忠秋,齐智利.γ-氨基丁酸调控采食量和缓解热应激的机制[J].动物营养学报,2014,26(1):49-53.

[19] SCHWARTZ M W,WOODS S C,PORTE D,et al.Central nervous system control of food intake[J].Nature,2000,404(6778):661-671.

[20] 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.  

[21] PORTE D,Jr,BASKIN D G,SCHWARTZ M W.Leptin and insulin action in the central nervous system[J].Nutrition Reviews,2002,60(10 Pt 2):S20-S29.

[22] SIMPSON K A,MARTIN N M,BLOOM S R.Hypothalamic regulation of food intake and clinical therapeutic applications[J].Arquivos Brasileiros de Endocrinologia & Metabologia,2009,53(2):120-128.

[23] 桑军亮,田科雄.瘦素调节动物采食量及能量代谢的研究进展[J].湖南饲料,2011(1):34-37.

[24] 梁亮,魏晓莉,孙彭利,等.新型黑皮质素4受体激动剂减肥作用研究[J].解放军药学学报,2009,25(5):386-390.

[25] MARSH D J,HOLLOPETER G,HUSZAR D,et al.Response of melanocortin-4 receptor-deficient mice to anorectic and orexigenic peptides[J].Nature Genetics,1999,21(1):119-122.  

[26] PIMENTEL G D,ROPELLE E R,ROCHA G Z,et al.The role of neuronal AMPK as a mediator of nutritional regulation of food intake and energy homeostasis[J].Metabolism:Clinical and Experimental,2013,62(2):171-178.  

[27] DANSINGER M L,GLEASON J A,GRIFFITH J L,et al.Comparison of the atkins,ornish,weight watchers,and zone diets for weight loss and heart disease risk reduction:a randomized trial[J].The Journal of the American Medical Association,2005,293(1):43-53.  

[28] WANG S B,KHONDOWE P,CHEN S F,et al.Effects of "Bioactive"amino acids leucine,glutamate,arginine and tryptophan on feed intake and mRNA expression of relative neuropeptides in broiler chicks[J].Journal of Animal Science and Biotechnology,2012,3:27.

[29] KHONDOWE P.脑室注射不同氨基酸对肉鸡采食的调控作用及其分子机制[D].硕士学位论文.广州:华南农业大学,2010.

[30] ROPELLE E R,PAULI J R,FERNANDES A M F,et al.A central role for neuronal AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) in high-protein diet-induced weight loss[J].Diabetes,2008,57(3):594-605.  

[31] 王诗男,蒋正尧.α-MSH对下丘脑葡萄糖敏感神经元活动的调制作用[J].青岛大学医学院学报,2011,47(2):95-97.

[32] KIM M S,PARK J Y,NAMKOONG C,et al.Anti-obesity effects of α-lipoic acid mediated by suppression of hypothalamic AMP-activated protein kinase[J].Nature Medicine,2004,10(7):727-733.  

[33] CHA S H,WOLFGANG M,TOKUTAKE Y,et al.Differential effects of central fructose and glucose on hypothalamic malonyl-CoA and food intake[J].Proceedings of the National Academy of Sciences of the United States of America,2008,105(44):16871-16875.  

[34] BELGARDT B F,OKAMURA T,BRVNING J C.Hormone and glucose signalling in POMC and AgRP neurons[J].The Journal of Physiology,2009,587(22):5305-5314.  

[35] OBICI S,FENG Z H,MORGAN K,et al.Central administration of oleic acid inhibits glucose production and food intake[J].Diabetes,2002,51(2):271-275.  

[36] SCHWINKENDORF D R,TSATSOS N G,GOSNELL B A,et al.Effects of central administration of distinct fatty acids on hypothalamic neuropeptide expression and energy metabolism[J].International Journal of Obesity,2011,35(3):336-344.  
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