miR-122对脂代谢影响的研究进展
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摘要
miR-122衍生自18号染色体上的单个基因组位点,与脂代谢关系密切,是脂代谢的转录后调控因子QmiR-122是调节脂代谢的关键miRNA,对调节脂代谢和保护肝脏功能起到至关重要的作用.运动能对脂代谢产生影响,很可能是通过调节miR-122的表达来实现的。通过综述miR-122对脂代谢的影响,探讨miR-122调节脂代谢的分子机制及生理学意义,展望运动影响miR-122调节脂代谢的可能性,以期为相关科研人员提供一个新思路,为解决超重与肥胖问题提供理论依据。
The miR-122 is not only a post-transcriptional regulator of lipid metabolism, but also the key miRNA of regulating lipid metabolism, and plays an important role in safeguarding liver as well, which isderived from a single genomic site on chromosome 18.The impact of exercise tolipid metabolism, maybe realized through adjustingmiR-122. With summarizing the influencing of, this article discusses the molecular mechanism and physiological significance of miR-122 to lipid metabolism, and outlooks the possibility of exercise influencing miR-122 lipid metabolism, in order to provide a new idea for relevant researchers and theoretical basis for solving the global problem of overweight and obesity.
The miR-122 is not only a post-transcriptional regulator of lipid metabolism, but also the key miRNA of regulating lipid metabolism, and plays an important role in safeguarding liver as well, which isderived from a single genomic site on chromosome 18.The impact of exercise tolipid metabolism, maybe realized through adjustingmiR-122. With summarizing the influencing of, this article discusses the molecular mechanism and physiological significance of miR-122 to lipid metabolism, and outlooks the possibility of exercise influencing miR-122 lipid metabolism, in order to provide a new idea for relevant researchers and theoretical basis for solving the global problem of overweight and obesity.
引文
[1]王来娣,郑云,蒋拾贝,等.Mirna在脂代谢中的研究进展[J].动物营养学报,2013,25(7):1446-1452.
[2] Ambros Victor. Micrornas:Tiny regulators with great potential[J]. Cell, 2001, 107(7):823-826.
[3] Iliopoulos Dimitrios, Drosatos Konstantinos, Hiyama Yaeko, et al. Microrna-370 controls the expression of microrna-122 and cpt1αand affects lipid metabolism[J] Journal of Lipid Research, 2010,51(6):1513-1523.
[4] Li C.,Zhang B. Micrornas in control of plant development[J] Journal of Cellular Physiology, 2015,231(2):303-313.
[5] RC Lee, RL Feinbaum, V Ambros. The c. Elegans heterochronic gene lin-4 encodes small rnas with antisense complementarity to lin-14[J]. Cell, 1993, 75(5):843.
[6] Singh N. K. Micrornas databases:Developmental methodologies,structural and functional annotations[J]. Interdiscip Sci,2017:1-21.
[7] Fu L. L.,Wen X.,Bao J. K.,et al. Microma-modulated autophagic signaling networks in cancer[J]. International Journal of Biochemistry&Cell Biology,2012, 44(5):733-736.
[8] AlvarezErviti L,Seow Y,Schapira AH,et al. Influence of microrna deregulation on chaperone-mediated autophagy andα-synuclein pathology in parkinson's disease[J].Cell Death&Disease, 2013, 4(3):e545.
[9] Zhang Zaiwei, Li Hu, Chen Shasha, et al. Knockdown of microrna-122 protects h9c2 cardiomyocytes from hypoxia-induced apoptosis and promotes autophagy[J]. Medical Science Monitor International Medical Journal of Experimental&Clinical Research, 2017,23:4284-4290.
[10] Ramasamy Subbiah, Velmurugan Ganesan, Rajan K.Shanmugha, et al. Mirnas with apoptosis regulating potential are differentially expressed in chronic exerciseinduced physiologically hypertrophied hearts[J]. Plos One,2015, 10(3):e0121401.
[11] Motavaf M, Safari S, Alavian S. M. Targeting micror-na-122:Walking on cutting edge of hepatitis c virus infection therapy[J]. Acta Virologica, 2014, 58(4):301-308.
[12] Rodriguez A, Griffiths-Jones S, Ashurst J. L., et al.Identification of mammalian microrna host genes and transcription units[J]. Genome Research,2004,14(10A):1902-1910.
[13] Saini Harpreet Kaur, Griffiths-Jones Sam,Enright Anton James. Genomic analysis of human microrna transcripts[J]. Proceedings of the National Academy of Sciences of the United States of America, 2007,104(45):17719-17724.
[14] Chang J.,Nicolas E,Marks D,et al. Mir-122,a mammalian liver-specific microrna, is processed from her mrna and may downregulate the high affinity cationic amino acid transporter cat-1[J]. Rna Biology,2004, 1(2):106-113.
[15] Coulouarn C,Factor VMAndersen J. B., Durkin M.E., et al. Loss of mir-122 expression in liver cancer correlates with suppression of the hepatic phenotype and gain of metastatic properties[J]. Oncogene,2009, 28(40):3526-3536.
[16] Xu H., He J. H., Xiao Z. D., et al. Liver-enriched transcription factors regulate microrna-122 that targets cutll during liver development[J]. Hepatology,2010, 52(4):1431-1442.
[17] Sethupathy P. Needles in the genetic haystack of lipid disorders:Single nucleotide polymorphisms in the microrna regulome[J]. Journal of Lipid Research,2013, 54(5):1168.
[18] Jopling C. Liver-specific microrna-122:Biogenesis and function[J]. Rna Biology, 2012,9(2):137-142.
[19] Esau C, Davis S, Murray S. F., et al. Mir-122 regulation of lipid metabolism revealed by in vivo antisense targeting[J]. Cell Metabolism,2006,3(2):87-98.
[20] M Lindow, S Kauppinen. Discovering the first microrna-targeted drug[J]. Journal of Cell Biology,2013,199(3):63-68.
[21] D Gatfield, G Le Martelot, CE Vejnar, et al. Integration of microrna mir-122 in hepatic circadian gene expression[J].Genes&Development, 2009, 23(11):1313.
[22] Hsu Shuhao, Wang Bo, Kota Janaiah, et al. Essential metabolic, anti-inflammatory, and anti-tumorigenic functions of mir-122 in liver[J]. Journal of Clinical Investigation,2012,122(8):2871-83.
[23] Tsai W. C., Hsu S. D., Hsu C. S., et al. Microrna-122 plays a critical role in liver homeostasis and hepatocarcinogenesis[J]. Journal of Clinical Investigation,2012, 122(8):2884-2897.
[24]朱磊,路瑛丽,冯连世,等.Microrna调节脂代谢的研究进展[J].中国体育科技,2016,52(3):61-68.
[25] Zinkhan E. K., Yu B., Schlegel A. Prenatal exposure to a maternal high fat diet increases hepatic cholesterol accumulation in intrauterine growth restricted rats in part through microrna-122 inhibition of cyp7al[J].Frontiers in Physiology,2018(9):645.
[26] Fu Q., Mcknight R. A., Yu X., et al. Growth retardation alters the epigenetic characteristics of hepatic dual specificity phosphatase 5[J].Faseb Journal Official Publication of the Federation of American Societies for Experimental Biology,2006,20(12):2127-2129.
[27] Ghosh J,Bose M,Roy S,et al. Leishmania donovani targets dicerl to downregulate mir-122, lower serum cholesterol, and facilitate murine liver infection[J].Cell Host&Microbe, 2013,13(3):277-288.
[28] Susanna Cirera Malene Birck,Peter K Busk,Merete Fredholm. Expression profiles of mirna-122 and its target cat1 in minipigs(sus scrofa)fed a high-cholesterol diet[J].Comparative Medicine, 2010, 60(2):136-41.
[29] Edwards Jason M., Neeb Zachary P., Alloosh Mouha-mad A., et al. Exercise training decreases store-operated ca2+entry associated with metabolic syndrome and coronary atherosclerosis[J].Cardiovascular Research,2010,85(3):631.
[30] Wu G. Y., Rui C., Chen J. Q., et al. Microrna-122 inhibits lipid droplet formation and hepatic triglyceride accumulation via yin yang 1[J].Cellular Physiology&Biochemistry,2017, 44(4):1651-1664.
[31] Y Lu, Z Ma, Z Zhang, et al. Yin yang 1 promotes hepatic steatosis through repression of farnesoid x receptor in obese mice[J]. Gut, 2014,63(1):170-178.
[32]荆文,路瑛丽,冯连世.Mirna对脂代谢的调节[J].中国运动医学杂志,2013,32(12):1129-1135.
[33] Safdar A, Abadi A, Akhtar M, et al.Mirna in the regulation of skeletal muscle adaptation to acute endurance exercise in c57bl/6j male mice[J].Plos One,2009, 4(5):e5610.
[34] Fernandes Tiago,Barretti Diego L,Soci Ursula P,et al. Abstract 19592:Exercise training prevents obesity normalizing cardiac mirna-208a and med 13 levels in obese zucker rats[J].Circulation, 2012,126(21):A19592.
[35] Cui S. F., Li W., Niu J., etc. Acute responses of circulating micrornas to low-volume sprint interval cycling[J]. Frontiers in Physiology, 2015,80(6).
[2] Ambros Victor. Micrornas:Tiny regulators with great potential[J]. Cell, 2001, 107(7):823-826.
[3] Iliopoulos Dimitrios, Drosatos Konstantinos, Hiyama Yaeko, et al. Microrna-370 controls the expression of microrna-122 and cpt1αand affects lipid metabolism[J] Journal of Lipid Research, 2010,51(6):1513-1523.
[4] Li C.,Zhang B. Micrornas in control of plant development[J] Journal of Cellular Physiology, 2015,231(2):303-313.
[5] RC Lee, RL Feinbaum, V Ambros. The c. Elegans heterochronic gene lin-4 encodes small rnas with antisense complementarity to lin-14[J]. Cell, 1993, 75(5):843.
[6] Singh N. K. Micrornas databases:Developmental methodologies,structural and functional annotations[J]. Interdiscip Sci,2017:1-21.
[7] Fu L. L.,Wen X.,Bao J. K.,et al. Microma-modulated autophagic signaling networks in cancer[J]. International Journal of Biochemistry&Cell Biology,2012, 44(5):733-736.
[8] AlvarezErviti L,Seow Y,Schapira AH,et al. Influence of microrna deregulation on chaperone-mediated autophagy andα-synuclein pathology in parkinson's disease[J].Cell Death&Disease, 2013, 4(3):e545.
[9] Zhang Zaiwei, Li Hu, Chen Shasha, et al. Knockdown of microrna-122 protects h9c2 cardiomyocytes from hypoxia-induced apoptosis and promotes autophagy[J]. Medical Science Monitor International Medical Journal of Experimental&Clinical Research, 2017,23:4284-4290.
[10] Ramasamy Subbiah, Velmurugan Ganesan, Rajan K.Shanmugha, et al. Mirnas with apoptosis regulating potential are differentially expressed in chronic exerciseinduced physiologically hypertrophied hearts[J]. Plos One,2015, 10(3):e0121401.
[11] Motavaf M, Safari S, Alavian S. M. Targeting micror-na-122:Walking on cutting edge of hepatitis c virus infection therapy[J]. Acta Virologica, 2014, 58(4):301-308.
[12] Rodriguez A, Griffiths-Jones S, Ashurst J. L., et al.Identification of mammalian microrna host genes and transcription units[J]. Genome Research,2004,14(10A):1902-1910.
[13] Saini Harpreet Kaur, Griffiths-Jones Sam,Enright Anton James. Genomic analysis of human microrna transcripts[J]. Proceedings of the National Academy of Sciences of the United States of America, 2007,104(45):17719-17724.
[14] Chang J.,Nicolas E,Marks D,et al. Mir-122,a mammalian liver-specific microrna, is processed from her mrna and may downregulate the high affinity cationic amino acid transporter cat-1[J]. Rna Biology,2004, 1(2):106-113.
[15] Coulouarn C,Factor VMAndersen J. B., Durkin M.E., et al. Loss of mir-122 expression in liver cancer correlates with suppression of the hepatic phenotype and gain of metastatic properties[J]. Oncogene,2009, 28(40):3526-3536.
[16] Xu H., He J. H., Xiao Z. D., et al. Liver-enriched transcription factors regulate microrna-122 that targets cutll during liver development[J]. Hepatology,2010, 52(4):1431-1442.
[17] Sethupathy P. Needles in the genetic haystack of lipid disorders:Single nucleotide polymorphisms in the microrna regulome[J]. Journal of Lipid Research,2013, 54(5):1168.
[18] Jopling C. Liver-specific microrna-122:Biogenesis and function[J]. Rna Biology, 2012,9(2):137-142.
[19] Esau C, Davis S, Murray S. F., et al. Mir-122 regulation of lipid metabolism revealed by in vivo antisense targeting[J]. Cell Metabolism,2006,3(2):87-98.
[20] M Lindow, S Kauppinen. Discovering the first microrna-targeted drug[J]. Journal of Cell Biology,2013,199(3):63-68.
[21] D Gatfield, G Le Martelot, CE Vejnar, et al. Integration of microrna mir-122 in hepatic circadian gene expression[J].Genes&Development, 2009, 23(11):1313.
[22] Hsu Shuhao, Wang Bo, Kota Janaiah, et al. Essential metabolic, anti-inflammatory, and anti-tumorigenic functions of mir-122 in liver[J]. Journal of Clinical Investigation,2012,122(8):2871-83.
[23] Tsai W. C., Hsu S. D., Hsu C. S., et al. Microrna-122 plays a critical role in liver homeostasis and hepatocarcinogenesis[J]. Journal of Clinical Investigation,2012, 122(8):2884-2897.
[24]朱磊,路瑛丽,冯连世,等.Microrna调节脂代谢的研究进展[J].中国体育科技,2016,52(3):61-68.
[25] Zinkhan E. K., Yu B., Schlegel A. Prenatal exposure to a maternal high fat diet increases hepatic cholesterol accumulation in intrauterine growth restricted rats in part through microrna-122 inhibition of cyp7al[J].Frontiers in Physiology,2018(9):645.
[26] Fu Q., Mcknight R. A., Yu X., et al. Growth retardation alters the epigenetic characteristics of hepatic dual specificity phosphatase 5[J].Faseb Journal Official Publication of the Federation of American Societies for Experimental Biology,2006,20(12):2127-2129.
[27] Ghosh J,Bose M,Roy S,et al. Leishmania donovani targets dicerl to downregulate mir-122, lower serum cholesterol, and facilitate murine liver infection[J].Cell Host&Microbe, 2013,13(3):277-288.
[28] Susanna Cirera Malene Birck,Peter K Busk,Merete Fredholm. Expression profiles of mirna-122 and its target cat1 in minipigs(sus scrofa)fed a high-cholesterol diet[J].Comparative Medicine, 2010, 60(2):136-41.
[29] Edwards Jason M., Neeb Zachary P., Alloosh Mouha-mad A., et al. Exercise training decreases store-operated ca2+entry associated with metabolic syndrome and coronary atherosclerosis[J].Cardiovascular Research,2010,85(3):631.
[30] Wu G. Y., Rui C., Chen J. Q., et al. Microrna-122 inhibits lipid droplet formation and hepatic triglyceride accumulation via yin yang 1[J].Cellular Physiology&Biochemistry,2017, 44(4):1651-1664.
[31] Y Lu, Z Ma, Z Zhang, et al. Yin yang 1 promotes hepatic steatosis through repression of farnesoid x receptor in obese mice[J]. Gut, 2014,63(1):170-178.
[32]荆文,路瑛丽,冯连世.Mirna对脂代谢的调节[J].中国运动医学杂志,2013,32(12):1129-1135.
[33] Safdar A, Abadi A, Akhtar M, et al.Mirna in the regulation of skeletal muscle adaptation to acute endurance exercise in c57bl/6j male mice[J].Plos One,2009, 4(5):e5610.
[34] Fernandes Tiago,Barretti Diego L,Soci Ursula P,et al. Abstract 19592:Exercise training prevents obesity normalizing cardiac mirna-208a and med 13 levels in obese zucker rats[J].Circulation, 2012,126(21):A19592.
[35] Cui S. F., Li W., Niu J., etc. Acute responses of circulating micrornas to low-volume sprint interval cycling[J]. Frontiers in Physiology, 2015,80(6).