脂肪组织转化关键因子的研究进展
Research Progress of Key Factors for the Transformation of Adipose Tissue

DOI: 10.12677/QRB.2015.22002, PP. 11-17

Keywords: 褐色脂肪组织，白色脂肪组织，转化
Brown Adipose Tissue, White Adipose Tissue, Transformation

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Abstract:

脂肪组织科分为褐色脂肪组织(Brown adipose tissue, BAT)和白色脂肪组织(white adipose tissue)。BAT为一种特化的产热组织，是小型哺乳动物非颤抖性产热的主要部位。PRDM16 (PR domain-con- taining 16)锌指蛋白在BAT中特异性表达，可触发BAT细胞中PGC-1α (Peroxisome proliferators-ac- tivated receptor-γcoactivator-1)和解偶联蛋白1基因等的表达，是促进褐色脂肪细胞形成的关键调控因子。BMP7 (Bone morphogenetic proteins 7)也可激活PRDM16和PGC-1α等基因的表达，刺激BAT细胞分化及产热增强。COXII (cyclooxygenase-2)、PPARα (peroxisome proliferator-activated receptor α)、PGC-1α是褐色脂肪细胞分化与代谢中的关键调控因子。在WAT中COXII是肾上腺素信号通路的一个效应分子，对于WAT中诱导形成褐色脂肪细胞是必需的。PPARα在BAT中的表达水平高于WAT，能诱导BAT中的产热相关基因的表达及原代褐色脂肪细胞的生成。PGC-1α也能诱导WAT中褐色脂肪细胞的形成，在褐色脂肪细胞分化的过程中PGC-1α表达量上升。本论文对脂肪转化过程中关键因子进行研究，并且对于小型哺乳动物的脂肪转化研究给出一些展望。
Adipose tissue is divided into brown adipose tissue (BAT) and white adipose tissue (WAT). BAT was a specialized thermogenic tissue, which was the main site of nonshivering thermogenesis in small mammals. PR domain-containing 16 (PRDM16) was a brown adipose determination factor. It was selectively expressed in BAT and induced the expression of α subunit of peroxisome proliferators-activated receptor-γcoactivator-1 (PGC-1α) and uncoupling protein 1. BMP7 could stimulate brown adipocyte differentiation and enhance thermogenesis by activating the expression PRDM16 and PGC-1α genes. COXII, PPARα and PGC-1α were the key regulatory factors of differentiation and metabolism in brown adipocyte. COXII was an effector molecule of adrenergic pathway in WAT. It was necessary for the formation of brown adipocytes. PPARα expression level in BAT was higher than WAT. It could induce the expression of thermogenesis related genes and promote the generation of primary brown adipocyte. PGC-1α also could induce the formation of brown adipocytes in WAT. In the process of brown adipocytes differentiation, PGC-1α expression level increased. In this paper, the key factors of transformation of adipose tissue were studied, and some prospects for the study of the fat tissue transformation of small mammals were given.

References

[1]	Cannon, B. and Nedergaard, J. (2004) Brown adipose tissue: Function and physiological significance. Physiological Reviews, 84, 277-359. http://dx.doi.org/10.1152/physrev.00015.2003
[2]	Vázquez-Vela, M.E.F., Torres, N. and Tovar, A.R. (2008) White adipose tissue as endocrine organ and its role in obesity. Archives of Medical Research, 39, 715-728. http://dx.doi.org/10.1016/j.arcmed.2008.09.005
[3]	Henry, S.L., Jonathan, G.B. and Ryan, J.W. (2012) White adipocytes: More than just fat depots. The International Journal of Biochemistry & Cell Biology, 44, 435-440. http://dx.doi.org/10.1016/j.biocel.2011.12.011
[4]	Galic, S., Oakhill, J.S. and Steinberg, G.R. (2010) Adipose tissue as an endocrine organ. Molecular and Cellular Endocrinology, 316, 129-139. http://dx.doi.org/10.1016/j.mce.2009.08.018
[5]	James, H.H. (2012) The adipocyte as an endocrine organ in the regulation of metabolic homeostasis. Neuropharmacology, 63, 57-75. http://dx.doi.org/10.1016/j.neuropharm.2011.12.010
[6]	Tews, D. and Wabitsch, M. (2011) Renaissance of brown adipose tissue. Hormone Research in Paediatrics, 75, 231- 239. http://dx.doi.org/10.1159/000324806
[7]	Rothwell, N.J. and Stock, M.J. (1983) Luxuskonsumption, diet-induced thermogenesis and brown fat: The case in favour. Clinical Science, 64, 19-23.
[8]	Clapham, J.C. (2012) Central control of thermogenesis. Neuropharmacology, 63, 111-123. http://dx.doi.org/10.1016/j.neuropharm.2011.10.014
[9]	Nakamura, K. and Morrison, S.F.A. (2008) Thermosensory pathway that controls body temperature. Nature Neuroscience, 11, 62-71. http://dx.doi.org/10.1038/nn2027
[10]	Brown, J.W., Sirlin, E.A. and Benoit, A.M. (2008) Activation of 5-HT1A receptors in medullary raphe disrupts sleep and decreases shivering during cooling in the conscious piglet. American Journal of Physiology. Regulatory, Integrative and Comparative Physiology, 63, 884-894. http://dx.doi.org/10.1152/ajpregu.00655.2007
[11]	Azzu, V. and Brand, M.D. (2010) The on-off switches of the mitochondrial uncoupling proteins. Trends in Biochemical Sciences, 35, 298-307. http://dx.doi.org/10.1016/j.tibs.2009.11.001
[12]	Birerdinc, A., Jarrar, M. and Stotish, T. (2013) Manipulating molecular switches in brown adipocytes and their precursors: A therapeutic potential. Progress in Lipid Research, 52, 51-61. http://dx.doi.org/10.1016/j.plipres.2012.08.001
[13]	Seale, P., Bjork, B. and Yang, W. (2008) PRDM16 controls a brown fat/skeletal muscle switch. Nature, 454, 961-967. http://dx.doi.org/10.1038/nature07182
[14]	Enerback, S. (2010) Human brown adipose tissue. Cell Metabolism, 11, 248-252. http://dx.doi.org/10.1016/j.cmet.2010.03.008
[15]	Cypess, A.M., Lehman, S. and Williams, G. (2009) Identification and importance of brown adipose tissue in adult humans. The New England Journal of Medicine, 360, 1509-1517. http://dx.doi.org/10.1056/NEJMoa0810780
[16]	Van, M., Lichtenbelt, W.D. and Vanhommerig, J.W. (2009) Cold-activated brown adipose tissue in healthy men. The New England Journal of Medicine, 360, 1500-1508. http://dx.doi.org/10.1056/NEJMoa0808718
[17]	Virtanen, K.A., Lidell, M.E. and Orava, J. (2009) Functional brown adipose tissue in healthy adults. The New England Journal of Medicine, 360, 1518-1525. http://dx.doi.org/10.1056/NEJMoa0808949
[18]	Cypess, A.M. and Kahn, C.R. (2010) Brown fat as a therapy for obesity and diabetes. Current Opinion Endocrinology, 17, 143-149. http://dx.doi.org/10.1097/MED.0b013e328337a81f
[19]	Frühbeck, G., Sesma, P. and Burrel, M.A. (2009) PRDM16: The interconvertible adipo-myocyte switch. Cell Biology, 19, 141-146. http://dx.doi.org/10.1016/j.tcb.2009.01.007
[20]	Kajimura, S., Seale, P. and Tomaru, T. (2008) Regulation of the brown and white fat gene programs through a PRDM16/CtBP transcriptional complex. Gene & Development, 22, 1397-1409. http://dx.doi.org/10.1101/gad.1666108
[21]	Chinnadurai, G. (2007) Transcriptional regulation by C-terminal binding proteins. The International Journal of Biochemistry & Cell Biology, 39, 1593-1607. http://dx.doi.org/10.1016/j.biocel.2007.01.025
[22]	Uldry, M., Yang, W. and St-Pierre, J. (2006) Complementary action of the PGC-1 coactivators in mitochondrial biogenesis and brown fat differentiation. Cell Metabolism, 3, 333-341. http://dx.doi.org/10.1016/j.cmet.2006.04.002
[23]	Balint, E., Lapointe, D. and Drissi, H. (2003) Phenotype discovery by gene expression profiling: Mapping of biological processes linked to BMP-2-mediated osteoblast differentiation. Journal of Cellular Biochemistry, 89, 401-426. http://dx.doi.org/10.1002/jcb.10515
[24]	Canalis, E., Economides, A.N. and Gazzerro, E. (2003) Bone morphogenetic proteins, their antagonists, and the skeleton. Endocrine Reviews, 24, 218-235. http://dx.doi.org/10.1210/er.2002-0023
[25]	Chen, D., Zhao, M. and Mundy, G.R. (2004) Bone morphogenetic proteins. Growth Factors, 22, 233-241. http://dx.doi.org/10.1080/08977190412331279890
[26]	Tseng, Y.H., Kokkotou, E. and Schulz, T.J. (2008) New role of bone morphogenetic protein 7 in brown adipogenesis and energy expenditure. Nature, 454, 1000-1004. http://dx.doi.org/10.1038/nature07221
[27]	Garavito, R.M. and Mulichak, A.M. (2003) The structure of mammalian cyclooxygenases. Annual Review Biophysics and Biomolecular Structure, 32, 183-206. http://dx.doi.org/10.1146/annurev.biophys.32.110601.141906
[28]	Davis, T.W., Zweifel, B.S. and O’Neal, J.M. (2004) Inhibition of cyclooxygenase-2 by celecoxib reverses tumor-in- duced wasting. The Journal of Pharmacology and Experimental Therapeutics, 308, 929-934. http://dx.doi.org/10.1124/jpet.103.063099
[29]	Fain, J.N., Ballou, L.R. and Bahouth, S.W. (2001) Obesity is induced in mice heterozygous for cyclooxygenase-2. Prostaglandins Other Lipid Mediators, 65, 199-209. http://dx.doi.org/10.1016/S0090-6980(01)00136-8
[30]	Guerra, C., Koza, R.A. and Yamashita, H. (1998) Emergence of brown adipocytes in white fat in mice is under genetic control: Effects on body weight and adiposity. The Journal of Clinical Investigation, 102, 412-420. http://dx.doi.org/10.1172/JCI3155
[31]	Gesta, S., Tseng, Y.H. and Kahn, C.R. (2007) Developmental origin of fat: tracking obesity to its source. Cell, 131, 242-256. http://dx.doi.org/10.1016/j.cell.2007.10.004
[32]	Vegiopoulos, A., Muller-Decker, K., Strzoda, D., Schmitt, I., Chichelnitskiy, E., Ostertag, A., et al. (2010) Cyclooxygenase-2 controls energy homeostasis in mice by de novorecruitment of brown adipocytes. Science, 328, 1158-1161. http://dx.doi.org/10.1126/science.1186034
[33]	Liang, H. and Ward, W.F. (2006) PGC-1α: A key regulator of energy metabolism. Advances Physiology Education, 30, 145-151. http://dx.doi.org/10.1152/advan.00052.2006
[34]	Uldry, M., Yang, W. and St-Pierre, J. (2006) Complementary action of the pgc-1 coactivators in mitochondrial biogenesis and brown fat differentiation. Cell Metabolism, 3, 333-341. http://dx.doi.org/10.1016/j.cmet.2006.04.002
[35]	Cao, W., Daniel, K.W. and Robidoux, J. (2004) P38 mitogen-activated protein kinase is the central regulator of cyclic amp-dependent transcription of the brown fat uncoupling protein 1 gene. Molecular and Cellular Biology, 24, 3057- 3067. http://dx.doi.org/10.1128/MCB.24.7.3057-3067.2004
[36]	Puigserver, P., Wu, Z. and Park, C.W. (1998) A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis. Cell, 92, 829-839. http://dx.doi.org/10.1016/S0092-8674(00)81410-5
[37]	Tiraby, C., Tavernier, G. and Lefort, C. (2003) Acquirement of brown fat cell features by human white adipocytes. The Journal of Biological Chemistry, 278, 33370-33376. http://dx.doi.org/10.1074/jbc.M305235200
[38]	Lin, J.D., Wu, P.H. and Tarr, P.T. (2004) Defects in adaptive energy metabolism with CNS-linked hyperactivity in PGC-1α null mice. Cell, 119, 121-135. http://dx.doi.org/10.1016/j.cell.2004.09.013
[39]	Karamanlidis, G., Karamitri, A. and Docherty, K. (2007) C/EBPb reprograms white 3T3-L1 preadipocytes to a brown adipocyte pattern of gene expression. Journal of Biological Chemistry, 282, 24660-24669. http://dx.doi.org/10.1074/jbc.M703101200
[40]	Kleiner, S., Nguyen-Tran, V. and Bare, O. (2009) PPARAδ agonism activates fatty acid oxidation via pgc-1α but does not increase mitochondrial gene expression and function. Journal of Biological Chemistry, 284, 18624-18633. http://dx.doi.org/10.1074/jbc.M109.008797
[41]	Tong, Y., Hara, A. and Komatsu, M. (2005) Suppression of expression of muscle-associated proteins by pparalpha in brown adipose tissue. Biochemical and Biophysical Research Communication, 336, 76-83. http://dx.doi.org/10.1016/j.bbrc.2005.08.041
[42]	Barbera, M.J., Schluter, A. and Pedraza, N. (2001) Peroxisome prolifera-tor-activated receptor alpha activates transcription of the brown fat uncoupling protein-1 gene. A link between regulation of the thermogenic and lipid oxidation pathways in the brown fat cell. Journal of Biological Chemistry, 276, 1486-1493. http://dx.doi.org/10.1074/jbc.M006246200
[43]	Cinti, S. (2005) The adipose organ. Prostaglandins, Leukotrienes and Essential Fatty Acids, 73, 9-15. http://dx.doi.org/10.1016/j.plefa.2005.04.010
[44]	Farmer, S.R. (2008) Brown fat and skeletal muscle: Unlikely cousins? Cell, 134, 726-727. http://dx.doi.org/10.1016/j.cell.2008.08.018

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