The Research Progress and Application Prospect of Uncoupling Protein 1 (UCP1)

作者: 高文荣 * , 张 麟 , 余婷婷 , 朱万龙 , 王政昆 :云南师范大学生命科学学院;

关键词: 解偶联蛋白-1(UCP1)产热调节信号通路转录调控肥胖治疗Uncoupling Protein 1 (Ucp1) Heat Production Adjustment Signal Path Transcription Regulation Obesity Treatment

摘要: UCP1是唯一在褐色脂肪组织(BAT)中表达的解偶联蛋白质。有别于解偶联蛋白家族其他成员的功能,UCP1的主要功能是参与BAT的产热调节和能量代谢来维持机体的能量代谢平衡。陆续有研究阐明调控UCP1参与BAT产热调节和能量代谢的分子机制,逐渐揭示了UCP1BAT能量代谢过程中涉及的信号通路与转录调控。这不仅让我们更好地理解UCP1BAT能量代谢调控中的重要作用,而且为基于褐色脂肪组织的肥胖治疗提供了理论依据。本文阐述了近年来研究发现的UCP1BAT能量代谢过程中发挥重要作用的信号通路与转录调控,并讨论了多种基于针对褐色脂肪组织的肥胖治疗手段的有效性与可行性。

Abstract: UCP1 is the only one expression of uncoupling protein in the brown adipose tissue (BAT). Different from the uncoupling protein family other member functions, UCP1’s main function is to participate thermogenic regulation and energy metabolism in BAT to maintain the body’s energy metabolic balance. In succession studies clarify regulation UCP1 participate heat production regulation and energy metabolism molecular mechanism in BAT, gradually reveals the UCP1 inBAT energy metabolic process involved in the signal path and transcription regulation. This not only let us better understand UCP1 inBAT energy metabolism control of the important role, but based on brown adipose tissue obesity treatment provides a theoretical basis. This paper describes the research in recent years UCP1 found in BAT energy metabolism process play an important role in the signal path and transcription regulation, and discussed based on various for brown adipose tissue obesity treatment of the effectiveness and feasibility.

文章引用: 高文荣 , 张 麟 , 余婷婷 , 朱万龙 , 王政昆 (2012) 解偶联蛋白-1(UCP1)的研究进展及其应用前景。 生物过程, 2, 128-137. doi: 10.12677/BP.2012.23021


[1] H. Jia, E. I. Lubetkin. Trends in quality-adjusted life-years lost contributed by smoking and obesity. American Journal of Preventive Medicine, 2010, 38(2): 138-144.

[2] Y. H. Tseng, A. M. Cypess and C. R. Kahn. Cellular bioenergetics as a target for obesity therapy. Nature Reviews Drug Discovery, 2010, 9(6): 465-482.

[3] W. P. Cawthorn, E. L. Scheller and O. A. MacDougald. Adipose tissue stem cells meet preadipocyte commitment: Going back to the future. Journal of Lipid Research, 2012, 53(2): 227-246.

[4] M. E. Harper, K. Green and M. D. Brand. The efficiency of cellular energy transduction and its implications for obesity. Annual Review of Nutrition, 2008, 28: 13-33.

[5] J. R. Speakman, D. A. Levitsky, D. B. Allison, et al. Set points, settling points and some alternativemodels: Theoretical options to understand how genes and environments combine to regulate body adiposity. Disease Models & Mechanisms, 2011, 4(6): 733.

[6] J. Himms-Hagen. Brown adipose tissue thermogenesis: Interdisciplinary studies. Afseb Journal, 1990, 4: 2890-2898.

[7] S. Hidaka, T. Kakuma, H. Yoshimatsu, S. Yasunaga, M. Kurokawa and T. Sakata. Melecular cloning of rat uncoupling protein 2 cDNA and its expression in genetically obese Zucker fatty (fa/fa) rats. Biochim-Biophys-Acta, 1998, 1389(3): 178-186.

[8] G. Solanes, A. Vidal-Puig, D. Grujlc, J. S. Flier and B. B. Lowell. The human uncoupling protein-3 gene. Genomic strueture, ehromosomal localization, and genetic basis to short and long form transcripts. The Journal of Biological Chemistry, 1997, 272(41): 25433-25436.

[9] W. Mao, X. X. Yu, A. Zhong, W. Li, J. Brush, S. W. Sherwood, S. H. Adams and G. Pan. UCP4, a novel brain-speciflc mitochondrial protein that reduces membrane potential in mammalian cells. FEBS-Letters, 1999, 443(3): 326-330.

[10] D. Ricquier, F. Bouillaud. The uncoupling protein homologues: UCP1, UCP2, UCP3, StUCP and AtUCP. Biochemical Journal, 2000, 345(2): 161-179.

[11] W. Jarmuszkiewicz, A. M. Almeids, A. E. Vercesi, F. E. Sluse and C. M. Sluse-Goffart. Proton re-uptake partitioning between uncoupling protein and ATP Synthase during benzohydroxamic acid-resistant state 3 respiration in tomato fruit 1 mitochondria. Biological Chemistry, 2000, 275: 13315-13320.

[12] D. W. Mount, 著. 钟扬, 王莉等, 译. 生物信息学[M]. 北京: 高等教育出版社, 2003: 212-215.

[13] P. Mayinger, M. Klingenberg. Labeling of two different regions of the nucleotide binding site of the uncoupling protein from brown adipose tissue mitochondria with two ATP-analogs. Biochemistry, 1992, 31(43): 10536-10543.

[14] 张敏. 解偶联蛋白(UCPs)与肥胖关系研究及UCP4基因在脂肪组织中的功能探讨[D]. 南京医科大学, 2008.

[15] K. S. Echtay. Mitochondrial uncoupling proteins—What is their physiological role? Free Radical Biology & Medicine, 2007, 43: 1351-1371.

[16] M. Jasrtroch, K. Withers and M. Klingenspor. Uncoupling protein 2 and 3 in marsupials: Identification, phylo-geny and gene expression in response to cold and fasting in Antechinus flavpes. Physiological Genomics, 2004, 17: 130-139.

[17] S. Rehnmark, A. C. Biabco, J. D. Kieffer and J. E. Silva. Transcriptional and post transcriptional mec. Anisms in uncoupling protein mRNA response to cold. Physiology, 1992, 262: E58- E67.

[18] M. Modriansky, D. L. Murdza-Lnglis, H. V. Patel, K. B. Free- man and K. D. Garlid. Identification by site-directed mutagene- sis of three arginines in uncoupling protein that are essential for nue- leotide binding and inhibition. The Journal of Biological Chem- istry, 1997, 272(40): 24759-24762.

[19] H. Esterbauer, H. Oberkofler, Y. M. Liu, D. Breban, E. Hell, F. Krempler and W. Patsch. Uncopling protein-1 mRNA expression in obese human subjects: The role of sequenee variations at the uncoupling protein-1 gene locus. The Journal of Lipid Research, 1998, 39(4): 834-844.

[20] D. Ricquier, L. Casteilla and F. Bouillaud. Mocular studies of the uncoupling protein. Faseb Journal, 1991, 5: 2237-2242.

[21] E. M. Rohlfs, K. W. Daniel, R. T. Premont, L. P. Kozak and S. Collins. Regulation of the uncoupling protein gene (UCP) by βl, β2, and β3-adrenergic receptor subtypes in immortalized brown adipose cell 1ines. Biological Chemistry, 1995, 270(18): l0723- 10732.

[22] S. Collins, K. W. Daniel, A. E. Petro and R. S. Surwit. Strain- specific response to beta 3-adrenergic receptor agonist treatment of diet-induced obesity in mice. Endocrinology, 1997, 138(l): 405-413.

[23] C. Pico, M. L. Bonet and A. Palou. Stimulation of uncoupling protein synthesis in white adipose tissue of mice treated with the beta 3-adrenergic agonist CGP-12177. Cellular and Molecular Life Sciences, 1998, 54(2): 191-195.

[24] S. R. Ross, L. Choy, R. A. Graves, N. Fox, V. Solevjeva, S. Klaus, D. Riquier and B. M. Spiegelman. Hibernoma formation in tresgenic mice and isolation of a brown adiposcye cell line expressing the uncopling protein gene. Proceedings of the National Academy of Sciences of USA, 1992, 89: 7561-7565.

[25] S. Saito, C. T. Saito and R. Shingai. Adaptive evolution of the uncoupling protein 1 gene contributed to the acquisition of novel nonshivering thermogenesis in ancestral eutherian mammals. Gene, 2008, 408(1-2): 37-44.

[26] M. V. Kumar, P. J. Scarpacer. Differential effects of retinoic acid on uncoupling Protein-1 and lepting gene expression. Journal of Endocrinology, 1998, 57(2): 237-243.

[27] N. Sasaki, E. Uchida, M. Nityama, T. Yoshida and M. Saito. Anti-obesity effects of seleetive agonists to the beta 3-adrenergic receptor in dogs & Recruitment of thermogenic brow-adipocytes and reduction of adiposity after chronic treatment with a beta 3-adrenergic agonist. Journal of Veterinary Medical Science, 1998, 60(4): 465-469.

[28] E. Savontaus, J. Rouru, O. Boss, R. Huupponenr and M. Koulu. Differential regulation of uncoupling proteins by chronic treatments with β3-adrenergic agonist BRL35135 and metformin in obese fa/fa Zucker rats. Biochemical and Biophysical Research Communications, 1998, 246(3): 899-904.

[29] R. Rabelo, A. Cammand and J. E. Silva. 3’-, 5’-cyclic adenosine monophosph ate-response scquences of the uncoupling proteins gene are sequentially recruited during darglitazonc-induced brown odipocyte differentiation. Endocrinology, 1997, 138(12): 5325- 5332.

[30] S. Klaus, L. Casteilla, F. Bouillaud and D. Ricquier. The uncoupling proteins UCPs a memhraeous mitochondrial ion earrier exclusively expressed in brown adipose tissue. Biochemistry, 1991, 23: 791-801.

[31] R. Burcelin, J. Kande, D. Ricquier and J. Girad. Changes in uncoupling protein and GLUT4 glucos transporter expressions in interscapular brown adipose tissue of diabetic rats: Relative roles of hyperglycaemia and hypoinsulinemia. Biochemical Journal, 1993, 291: 109-113.

[32] P. J. Searpace, M. Matheny, B. H. Pollock and N. Tumer. Leptin increases uncoupling protein expression and energy expenditure. American Journal of Physiology, 1997, 273(1): E226-E230.

[33] P. J. Scarpace, M. Matheny. Leptin induction of UCP1 gene expression is dependent on sympathetic innervation. American Journal of Physiology, 1998, 275(2): E259-E264.

[34] S. P. Commins, P. M. Watson, M. A. Padgett, A. Dudley. G. Argyropoulos and T. W. Gettys. Induction of uncoupling protein expression in brown and white adipose tissue by leptin. Endo- crinology, 1999, 140(l): 292-300.

[35] D. X. Tan, L. Manchester, L. Fuentes-Broto, et al. Significance and application of melatonin in the regulation of brown adipose tissue metabolism: Relation to human obesity. Obesity Reviews, 2011, 12(3): 167-188.

[36] S. P. Vickers, H. C. Jackson and S. C. Cheetham. The utility of animal models to evaluate novel anti-obesity agents. British Journal of Pharmacology, 2011, 164(4): 1248-1262.

[37] P. G. Shekelle, M. L. Hardy, S. C. Morton, M. Maglione, W. A. Mojica, M. J. Suttorp, et al. Efficacy and safety of ephedra and ephedrine for weight loss and athletic performance: A meta- analysis. The Journal of the American Medical Association, 2003, 289(12): 1537-1545.

[38] J. R. Speakman, D. A. Levitsky, D. B. Allison, et al. Set points, settling points and some alternative models: Theoretical options to understand how genes and environments combine to regulate body adiposity. Disease Models & Mechanisms, 2011, 4(6): 733.

[39] R. L. Van, D. A. Roncari. Complete differentiation in vivo of implanted cultured adipocyte precursors from adult rats. Cell Tissue Research, 1982, 225(3): 557-566.

[40] J. Nedergaard, B. Cannon. The changed metabolic world with humanbrown adipose tissue: Therapeutic visions. Cell Metabolism, 2010, 11(4): 268-272.

[41] 张麟, 朱万龙, 王政昆等. 褐色脂肪组织分化及其调节机制研究进展[J]. 生物过程, 2011, 1: 13-17.