消渴丸对3T3-L1前脂肪细胞增殖及分化的影响
|
摘要
目的：
1.研究消渴丸对3T3-L1前脂肪细胞增殖过程的影响；
2.研究消渴丸对3T3-L1前脂肪细胞分化过程的影响。
方法：
1.制备大鼠消渴丸含药血清,培养小鼠3T3-L1前脂肪细胞,用XTT比色法检测消渴丸含药血清(5%、2.5%)对3T3-L1前脂肪细胞的增殖的影响；
2.应用不同浓度的消渴丸直接作用于3T3-L1前脂肪细胞,使用XTT比色法测定细胞增殖情况；
3.应用含消渴丸及各组分的分化培养基作用于3T3-L1前脂肪细胞,诱导分化至第8天,油红O脂肪染色观察及评价细胞分化情况,异丙醇萃取法测定其对细胞内脂肪积聚的影响。
结果：
1.高浓度(2000μg/L)消渴丸及消渴丸纯中药成分直接加药对3T3-L1前脂肪细胞增殖有抑制作用,差异有极显著意义；
2.油红O染色、异丙醇萃取法提示中等浓度(200μg/L)的消渴丸对3T3-L1前脂肪细胞的分化没有明显影响。
结论：
高浓度(2000μg/L)的消渴丸及消渴丸纯中药成分对小鼠3T3-L1前脂肪细胞的增殖有明显抑制作用；中等浓度(200μg/L)的消渴丸对3T3-L1前脂肪细胞的分化没有明显影响。
Objectives:
1. To investigate the effects of Xiaokewan on the proliferation of3T3-L1preadipocytes;
2. To investigate the effects of Xiaokewan on the differentiation of3T3-L1preadipocytes.
Methods:
1. Rat drug-containing serum was prepared for cell culture.3T3-L1preadipocytes were cultured in the presence of Xiaokewan containing serum (5%,2.5%). XTT assay was applied to evaluate the cell growth;
2.3T3-L1preadipocytes were cultured in the presence of Xiaokewan of different concentrations. XTT assay was applied to evaluate the cell proliferation;
3.3T3-L1preadipocytes were induced to differentiate to adipocytes in both treated groups containing Xiaokewan and the control group. Oil red O staining method was used to assess the lipid accumulation in adipocytes.
Results:
1. High concentration of Xiaokewan(2000μg/i) inhibited the prolifeiative activity of3T3-L1preadipocytes;
2. Moderate level of Xiaokewan had no effect on the differentiation of3T3-L1preadipocytes.
Conclusions:
Our study discovered that Xiaokewan inhibited the proliferation of3T3-L1preadipocytes, but no effect was observed in the differentiation of3T3-L1preadipocytes.
1.研究消渴丸对3T3-L1前脂肪细胞增殖过程的影响；
2.研究消渴丸对3T3-L1前脂肪细胞分化过程的影响。
方法：
1.制备大鼠消渴丸含药血清,培养小鼠3T3-L1前脂肪细胞,用XTT比色法检测消渴丸含药血清(5%、2.5%)对3T3-L1前脂肪细胞的增殖的影响；
2.应用不同浓度的消渴丸直接作用于3T3-L1前脂肪细胞,使用XTT比色法测定细胞增殖情况；
3.应用含消渴丸及各组分的分化培养基作用于3T3-L1前脂肪细胞,诱导分化至第8天,油红O脂肪染色观察及评价细胞分化情况,异丙醇萃取法测定其对细胞内脂肪积聚的影响。
结果：
1.高浓度(2000μg/L)消渴丸及消渴丸纯中药成分直接加药对3T3-L1前脂肪细胞增殖有抑制作用,差异有极显著意义；
2.油红O染色、异丙醇萃取法提示中等浓度(200μg/L)的消渴丸对3T3-L1前脂肪细胞的分化没有明显影响。
结论：
高浓度(2000μg/L)的消渴丸及消渴丸纯中药成分对小鼠3T3-L1前脂肪细胞的增殖有明显抑制作用；中等浓度(200μg/L)的消渴丸对3T3-L1前脂肪细胞的分化没有明显影响。
Objectives:
1. To investigate the effects of Xiaokewan on the proliferation of3T3-L1preadipocytes;
2. To investigate the effects of Xiaokewan on the differentiation of3T3-L1preadipocytes.
Methods:
1. Rat drug-containing serum was prepared for cell culture.3T3-L1preadipocytes were cultured in the presence of Xiaokewan containing serum (5%,2.5%). XTT assay was applied to evaluate the cell growth;
2.3T3-L1preadipocytes were cultured in the presence of Xiaokewan of different concentrations. XTT assay was applied to evaluate the cell proliferation;
3.3T3-L1preadipocytes were induced to differentiate to adipocytes in both treated groups containing Xiaokewan and the control group. Oil red O staining method was used to assess the lipid accumulation in adipocytes.
Results:
1. High concentration of Xiaokewan(2000μg/i) inhibited the prolifeiative activity of3T3-L1preadipocytes;
2. Moderate level of Xiaokewan had no effect on the differentiation of3T3-L1preadipocytes.
Conclusions:
Our study discovered that Xiaokewan inhibited the proliferation of3T3-L1preadipocytes, but no effect was observed in the differentiation of3T3-L1preadipocytes.
引文
1.陈兴宝,唐玲,陈慧云.2型糖尿病并发症对患者治疗费用的影响评估。中国糖尿病杂志,2003,11(4)：238-241
2.牛云飞,陈晓雯.消渴丸对胰岛p细胞功能和胰岛素抵抗的影响.中国现代中药,2006,8(6),26-28
3.王喜军.中药血清药物化学的研究动态及发展趋势.中国中药杂志,2006,31(10)：789-792
4. Trayhurn P. Beattie JH. Physiological role of adipose tissue:white adipose tissue as an endocrine and secretory organ. Proc Nutr Soc,2001,60:329-339
5. Holst D, Grimaldi PA. New factors in the regulation of adipose differentiation and metabolism. Curr Opin Lipidol,2002,13:241-245
6. Greenberg AS, McDaniel ML. Identifying the links between obesity, insulin resistance and beta-cell function:potential role of adipocyte-derived cytokines in the pathogenesis of type 2 diabetes. Eur J Clin Invest,2002,13:24-34
7. Prins J B, Orahilly S. Regulation of adipose cell number in man. Clin Sci,1997,92: 3-11
8. Green, H. & Kehinde, O. (1979) Formation of normally differentiated subcutaneous fat pads by an established preadipose cell line. Cell Physiol.101:169-172
9. Novikoff, A. B. Novikoff, P. M. Rosen, O. M. & Rubin, C. S. Organelle relationships in cultured 3T3-L1 preadipocytes. J. Cell Biol,1980,87:180-196
10. Snijdcr MB, Zimmet PZ, Visser M, et al. Independent and opposite association of waist and hip circumferences with diabetes, hypertension and dyslipidemia:the Aus Diab Study [J]. Int J Obes Relat Metab Disord,2004,28(3):402-409
11. Felber JP, Acheson KJ, Tappy L. From obesity to diabetes. New York:John Wiley&Sons, Inc,1993,21-25
12. Unger RH. Lipotoxicity in the pathogenesis of obesity-dependent NIDDM [J]. Diabetes,1995,44:863-870
13. Rosen K D, Walkey C J, Puigserver P, et al. Transcriptional regulation of adipogensis [J]. Genes Dev,2000,14:1293-1307
14.吴楠,崔恒.XTT比色法在细胞活性检测中的应用.国外医学临床生物化学与检验学分册.1998,19(5)：204-206
15.韩笑,刘建勋,林成仁.血清药理学关键问题的存疑与讨论.中药药理与临床,2009：25(2)：122-124
16.张红敏,谢春光,陈世伟.含药血清体外药理试验的评价[J].中国中西医结合杂志,2004,24(8)：741-745
17.张声鹏,施旭光,桂蜀华.关于中药血清药理学中血清供体动物是否造模的思考.中国中西医结合杂志,2001,21(5)：388-389
18.刘成海.中药复方体外药效研究思考.中药新药与临床药理.2000；11(1)：53-57
19.赵万红,曹永孝,袁泽飞.中药血清药理学的方法学探讨.中药新药与临床药理2002；13(2)：122-124
20.黄坚,陈长勋,李仪奎.用血清实验法观察小青龙汤对离体豚鼠气管平滑肌的作用.中药药理与临床1995；(6)：12-13
21. Ramir Zaearias JL. Castro MnnozledoF, kuriHcuch W. Quantitation of adipose conversion and triglycerides by staining intracytoplasmic lipids with oil red O. Histochemistry,1992,97(6):493
1. World Health Organization. Obesity and overweight.2006 September. http://www.who.int/mediacentre/factsheets/fs311/en/index.html
2. Trayhurn P, Beattie JH. Physiological role of adipose tissue:white adipose tissue as an endocrine and secretory organ. Proc Nutr Soc,2001,60:329-339
3. Greenberg AS, McDaniel ML. Identifying the links between obesity, insulin resistance and beta-cell function:potential role of adipocyte-derived cytokines in the pathogenesis of type 2 diabetes. Eur J Clin Invest,2002,13:24-34
4. ZukP A, zhu M, Ashjian P, et al. Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell.2002,13:4279-4295
5. Taylor SM, Jones PA. Multiple new phenotypes induced in 10T1/2 and 3T3 cells treated with 5-Azacytidine. Cell,1979,17:771-779
6. Dani C, Smith AG, Dessolin S, et al. Differentiation of embryonic stem cells into adipocyte in vitro. J Cell Sci,1997,110:1279-1285
7. Pittenger MF, Mackay AM, Beck SC, et al. Multilineage po tential of adult human mesenchymal stem cells. Science,1999,284:143-147
8. Konieczny SF. Emerson CP Jr.5-Azacytidine induction of stable mesodermal stem cell lineages from 10T1/2 cells:evidence for regulatory genes controlling determination. Cell,1984,38(3):791-800
9. Prins J B, Orahilly S. Regulation of adipose cell number in man. Clin Sci,1997,92: 3-11
10. Ailhaud G, Grimaldi P, Negnel R, et al. Cellular and molecular aspects of adipose tissue development [J]. Annu Rev Nutr,1992(12):207-33
11. Pilgrim C. DNA synthesis and differentiation in developing white adipose tissue [J]. Dev Biol,1971(26):69-76
12. Ono M, Aratani Y, Kitagawa I, et al. Ascorbic acid phosphate stimulates type IVcollagen synthesis and accelerates adipose conversion of 3T3 preadipocytes [J]. Exp Cell Res,1987.87:309-314
13. Rosen K D, Walkey C J, Puigserver P, et al. Transcriptional regulation of adipogensis [J]. Genes Dev,2000,14:1293-1307
14. Ntambi JM, Kim YC. Adipocyte differentiation and gene expression [J]. J Nutr,2000, 130(12):3122S-3126S
15. Miller J, Wilson H, Faust IM, et al. Demonstration of de novo production of adipocytes in adult rats by biochemical and radioautographic techniques [J]. J Lipid Res,1984,25:336-347
16. Tang QQ, Otto TC, Lane MD. Mitotic clonal expansion:A synchronous process required for adipogenesis. Proc Nail Acad Sci USA,2003,100:44-49
17. Ailhaud G. Early adipocyte differentiation. Biochem Soc Trans,1996,24:400-402
18. Tengku-Muhammad T.S., Hughes T.R., Cryer A., Ramji D.P. Differential regulation of lipoprotein lipase in the macrophage J774.2 cell line by cytokines. Cytokine,1996, 8 (7),525-533
19. Wu Z, Bucher NL, Farmer SR. Induction of peroxisome proliferator-activated receptor gamma during the conversion of 3T3 preadipocytes into adipocytes is mediated by C/EBP beta, C/EBP delta and glucocorticoids. Mol Cell Biol,1996,16: 4128-4136
20. Chawla, A., M. A. Lazar. Peroxisome proliferator and retinoid signaling pathways co-regulate preadipocyte pheonotype and survival. Proc. Natl. Acad. Sci. USA 1994, 91:1786-1790
21. Spiegelman BM, Farmer SR. Decreases in tubulin and actin gene expression prior to orphological differentiation of 3T3 adipocytes. Cell,1982,29:53-60
22. Spiegelman, B. M., H. Green. Cyclic AMP-mediated control of lipogenic enzyme synthesis during adipose differentiation of 3T3 cells. Cell 1981,24:503-510
23. Paulauskis J. D., H. S. SUL. Cloning and expression of mouse fatty acid synthase and other specific mRNAs. Developmental and hormonal regulation in 3T3-L1 cells. J Biol Chem.1988,263:7049-7054
24. Weiner, F. R., P. J. Smith, S. Wertheimer, C. S. Rubin. Regulation of gene expression by insulin and tumor necrosis factor alpha in 3T3-L1 cells. Modulation of the transcription of genes encoding acyl-CoA synthetase and stearoyl-CoA esaturase-1. J. Biol. Chem.1991,266:23525-23528
25. Alessi, M. C., F. Peiretti, P. Morange, M. Henry, G. Nalbone, I. Juhan-Vague. Production of plasminogen activator inhibitor 1 by human adipose tissue:possible link between visceral fat accumulation and vascular disease. Diabetes 46:860-867, 1997
26. Choy, L. N., B. M. Spiegelman. Regulation of alternative pathway activation and C3a production by adipose cells. Obesity Res.4:521-532,1996
27. Dobson, D. E, A. Kambe, E. Block, T. Dion, H. Lu, J. Castellot JR, B. M. Spiegelman. 1-Butyryl-glycerol:a novel angiogenesis factor secreted by differentiating adipocytes. Cell 61:223-230,1990
28. Jones, B. H., M. K. Standridge, N. Moustaid. Angiotensin Ⅱ increases lipogenesis in 3T3-L1 and human adipose cells. Endocrinology 138:1512-1519,1997
29. Ziouzenkova O, Orasanu G, Sukhova G et al. Asymmetric Cleavage of Beta-Carotene Yields a Transcriptional Repressor of Retinoid X Receptor and Peroxisome Proliferator-activated Receptor Responses [J]. Molecular Endocrinology,2007,21(1): 77-88
30. Green S. PPAR:A Mediator of Peroxisome Proliferator action [J]. Mutation Research, 1995,333(1-2):101-109
31. Akiyama TE, Lambert G, Nico C.J et al. Peroxisome Proliferator-activated Preceptor Beta/delta Regulates very Low Density Lipoprotein Production and Catabolism in Mice on a Western Diet [J]. J Biol Chem,2004,279(20):20874-20881
32. Grimaldi PA. The Roles of PPARs in Adipocyte Differentiation [J]. Progress Lipid Research,2001,40(4):269-281
33. Schoonjans K, Staels B, Auwers J. The peroxisome proliferator activated receptor and their effects on lipid metabolism and adipocyte differentiation. Biochem Biophys Acta.1996,1302(2):93-109
34. Saladin R, Fajas L, Dana S, et al. Differential regulation of peroxisome proliferator activated receptor gammal(PPAR-gammal)and PPAR-gamma2 messenger RNA expression in the early stages ofadipogenesis. Cell Growth Differ,1999,10(1):43-44
35. Tontonoz P, Singer S, Forman B M, et al. Terminal Differentiation of Human Liposarcoma Cells Induced by Ligands for Peroxisome Proliferator-aetivated Receptor Gamma and the Retinoid X Receptor [J]. Proc Nati Aca Sci USA,1997, 94(1):237-241
36. Madsen L, Petersen R K, Sorensen M B, et al. Adipocyte Differentiation of 3T3-L1 Preadipocytes is Dependent on Lipoxygenase Activity During the Initial Stages of the Differentiation Process [J]. Biochemical Journal,2003,375(3):539-549
37. Rosen ED, Sarraf AE, Troy G, et al. PPAR gamma is required for the differentiation of adipose tissue in vivo and in vitro. Mol Cell,1999,4:611-617
38. Wright HM, Clish CB, Spiegelman BM. A synthetic antagonist for the peroxisome proliferator-activated gamma ligand inhibits adipocyte differentiation. J Biol Chem,2000,275:1873-1877
39. Barroso IM, Gurnell VE, ORahilly S. Dominant negative mutations in human PPAR. gamma associated with severe insulin resistance, diabetes mellitus and hypertension. Nature,1999,402:880-883
40. Diehl AM, Michaelson P, Yang SQ. Selective Induction of CCAAT/enhancer Binding Protein Isoforms Occurs During Rat Liver Development [J]. Gastroenterology,1994, 106(6):1625-1637
41. Li X, Huang HY, Chen JG, et al. Lactacystin Inhibits 3T3-L1 Adipoeyte Differentiation through Induction of CHOP-10 expression [J]. Biochemical and Biophysical Research Communications,2006,350(1):1-6
42. Yeh WC, Cao Z, Mcknight SL. Cascade regulation of terminal adipocyte differentiation by three members of the C/EBP family of leucine zipper proteins. Genes&Dev,1995,15:168-181
43. Tanaka T, Yoshida N, Akira S. Defective adipocyte differentiation in mice lacking the C/EBPβ and/or C/EBPδ gene. EMBO J,1997,16:7432-7443
44. Cheung K J, Tzameli I, Pissios et al. Xanthine Oxidoreductase is a Regulator of Adipogenesis and PPARgamma Activity [J]. Cel Meta,2007,5(2):115-128
45. Choe S S, Choi A H, Lee J W et al. Chronic Activation of Liver X Receptor Induces β-cell Apoptosis Through Hyperactivation of Lipogenesis [J]. Diabetes,2007,56(6): 1534-1543
46. Lord E, Murphy B D, Desmarais J A, et al. Modulation of Peroxisome Proliferator-activated Receptor delta and Gamma Transcripts in Swine Endometrial Tissue During Early Gestation [J]. Reproduction,2006,131(5):929-942
47. Castro M F, Beltran L A, Kuri H W, el al. Commitment of 3T3-F442A Cell to Adipocyte Differentiation Takes Place During the First 24-36h after Adipogenic Stimulation:TNF-alpha inhibits commitmen [J]. Exp Cell Res,2003,2284(2): 163-172
48. Daya S, Loughlin A J, Macqueen H A. Culture and Differentiation of Preadipocytes in Two dimensional and Three-dimensional in Vitro Systems [J]. Exp Cell Res,2007, 75(5):360-370
49. Wang Y, Kim K A, Kim J H, et al. Pref-1, a Preadipocyte Secreted Factor that Inhibits Adipogenesis [J]. J Nutr,2006,136(12):2953-2956
50. LI S X, SONG H D. The Function of Pref-1 in Adipocyte Differentiation [J]. Intl Journal of Endo Met,2006,26(1):41-43
51. Macdougald OA, Lane MD. Transcriptional regulation of gene expression during adipocyte differentiation [J]. Annu Rev Biochem,1995,64:345-373
52. Kim CS, Kawada T, Kwon BS, et al. Macrophage inflammatory protein related protein-2, a novel CC chemokine, can regulate preadipocyte migration and adipocyte differentiation [J]. FEBS Lett,2003,548(1-3):125-130
53. Schmidt M, Park BH, Davis, et al. Adipose conversion of 3T3-L1 cells in a serum free culture system depends on epidermal growth factor, insulin-like growth factor, corticosterone and cyclic AMP [J]. J Biol Chem,1990,165:15489-15495
54. Kim S,Whelan J, Clyacombe K, et al. Angiotensin Ⅱ Increases Leptin Secretion by 3T3-L1 and Human Adipocytes Via a Prostaglandin-independent Mechanism [J]. Journal of Nutrition,2002,132(6):1135-1140
55. Wheatcroft S B, Keamey M T, Shah A M, et al. IGF-binding protein-2 protects against the development d obesity and insulin resistance [J]. Diabetes.2007,56(2): 285-294
56. Zhang H, Noohr J, Jensen C H, et al. Insulin-like Growth factor-1/insulin Bypasses Pref-1/FAl-mediated Inhibition of Adipocyte Differentiation [J]. J Biol logical Chem, 2003,278(23):20906-20914
57. Rosen C J, Ackert-Bicknell C L, Adamo M L. Congenic Mice with Low Serum IGF-1 have Increased Body Fat, Reduced Bone Mineral Density, and an Altered Osteoblast Differentiation Program [J]. Bone,2004,35(5):1046-1058
58. Negrel R, Kim JB, Wright HM, et al. Prostacyclin as a potent effector of adipose-cell differentiation [J]. Biochem J,1989,257:399
59. Vassaux G et al. Differential response of preadipocytes and adipocytes to prostacyclin and prostaglandin E2:Physiological implications [J]. Endocrinology,1992,131:2393
60. Smas CM, Chen I, Zhao L, et al. Transcriptional repression of pref-1 by glucocorticoid promotes 3T3-L1 adipocyte differentiation [J]. J Biol Chem,1999, 274(6):12632-12641
2.牛云飞,陈晓雯.消渴丸对胰岛p细胞功能和胰岛素抵抗的影响.中国现代中药,2006,8(6),26-28
3.王喜军.中药血清药物化学的研究动态及发展趋势.中国中药杂志,2006,31(10)：789-792
4. Trayhurn P. Beattie JH. Physiological role of adipose tissue:white adipose tissue as an endocrine and secretory organ. Proc Nutr Soc,2001,60:329-339
5. Holst D, Grimaldi PA. New factors in the regulation of adipose differentiation and metabolism. Curr Opin Lipidol,2002,13:241-245
6. Greenberg AS, McDaniel ML. Identifying the links between obesity, insulin resistance and beta-cell function:potential role of adipocyte-derived cytokines in the pathogenesis of type 2 diabetes. Eur J Clin Invest,2002,13:24-34
7. Prins J B, Orahilly S. Regulation of adipose cell number in man. Clin Sci,1997,92: 3-11
8. Green, H. & Kehinde, O. (1979) Formation of normally differentiated subcutaneous fat pads by an established preadipose cell line. Cell Physiol.101:169-172
9. Novikoff, A. B. Novikoff, P. M. Rosen, O. M. & Rubin, C. S. Organelle relationships in cultured 3T3-L1 preadipocytes. J. Cell Biol,1980,87:180-196
10. Snijdcr MB, Zimmet PZ, Visser M, et al. Independent and opposite association of waist and hip circumferences with diabetes, hypertension and dyslipidemia:the Aus Diab Study [J]. Int J Obes Relat Metab Disord,2004,28(3):402-409
11. Felber JP, Acheson KJ, Tappy L. From obesity to diabetes. New York:John Wiley&Sons, Inc,1993,21-25
12. Unger RH. Lipotoxicity in the pathogenesis of obesity-dependent NIDDM [J]. Diabetes,1995,44:863-870
13. Rosen K D, Walkey C J, Puigserver P, et al. Transcriptional regulation of adipogensis [J]. Genes Dev,2000,14:1293-1307
14.吴楠,崔恒.XTT比色法在细胞活性检测中的应用.国外医学临床生物化学与检验学分册.1998,19(5)：204-206
15.韩笑,刘建勋,林成仁.血清药理学关键问题的存疑与讨论.中药药理与临床,2009：25(2)：122-124
16.张红敏,谢春光,陈世伟.含药血清体外药理试验的评价[J].中国中西医结合杂志,2004,24(8)：741-745
17.张声鹏,施旭光,桂蜀华.关于中药血清药理学中血清供体动物是否造模的思考.中国中西医结合杂志,2001,21(5)：388-389
18.刘成海.中药复方体外药效研究思考.中药新药与临床药理.2000；11(1)：53-57
19.赵万红,曹永孝,袁泽飞.中药血清药理学的方法学探讨.中药新药与临床药理2002；13(2)：122-124
20.黄坚,陈长勋,李仪奎.用血清实验法观察小青龙汤对离体豚鼠气管平滑肌的作用.中药药理与临床1995；(6)：12-13
21. Ramir Zaearias JL. Castro MnnozledoF, kuriHcuch W. Quantitation of adipose conversion and triglycerides by staining intracytoplasmic lipids with oil red O. Histochemistry,1992,97(6):493
1. World Health Organization. Obesity and overweight.2006 September. http://www.who.int/mediacentre/factsheets/fs311/en/index.html
2. Trayhurn P, Beattie JH. Physiological role of adipose tissue:white adipose tissue as an endocrine and secretory organ. Proc Nutr Soc,2001,60:329-339
3. Greenberg AS, McDaniel ML. Identifying the links between obesity, insulin resistance and beta-cell function:potential role of adipocyte-derived cytokines in the pathogenesis of type 2 diabetes. Eur J Clin Invest,2002,13:24-34
4. ZukP A, zhu M, Ashjian P, et al. Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell.2002,13:4279-4295
5. Taylor SM, Jones PA. Multiple new phenotypes induced in 10T1/2 and 3T3 cells treated with 5-Azacytidine. Cell,1979,17:771-779
6. Dani C, Smith AG, Dessolin S, et al. Differentiation of embryonic stem cells into adipocyte in vitro. J Cell Sci,1997,110:1279-1285
7. Pittenger MF, Mackay AM, Beck SC, et al. Multilineage po tential of adult human mesenchymal stem cells. Science,1999,284:143-147
8. Konieczny SF. Emerson CP Jr.5-Azacytidine induction of stable mesodermal stem cell lineages from 10T1/2 cells:evidence for regulatory genes controlling determination. Cell,1984,38(3):791-800
9. Prins J B, Orahilly S. Regulation of adipose cell number in man. Clin Sci,1997,92: 3-11
10. Ailhaud G, Grimaldi P, Negnel R, et al. Cellular and molecular aspects of adipose tissue development [J]. Annu Rev Nutr,1992(12):207-33
11. Pilgrim C. DNA synthesis and differentiation in developing white adipose tissue [J]. Dev Biol,1971(26):69-76
12. Ono M, Aratani Y, Kitagawa I, et al. Ascorbic acid phosphate stimulates type IVcollagen synthesis and accelerates adipose conversion of 3T3 preadipocytes [J]. Exp Cell Res,1987.87:309-314
13. Rosen K D, Walkey C J, Puigserver P, et al. Transcriptional regulation of adipogensis [J]. Genes Dev,2000,14:1293-1307
14. Ntambi JM, Kim YC. Adipocyte differentiation and gene expression [J]. J Nutr,2000, 130(12):3122S-3126S
15. Miller J, Wilson H, Faust IM, et al. Demonstration of de novo production of adipocytes in adult rats by biochemical and radioautographic techniques [J]. J Lipid Res,1984,25:336-347
16. Tang QQ, Otto TC, Lane MD. Mitotic clonal expansion:A synchronous process required for adipogenesis. Proc Nail Acad Sci USA,2003,100:44-49
17. Ailhaud G. Early adipocyte differentiation. Biochem Soc Trans,1996,24:400-402
18. Tengku-Muhammad T.S., Hughes T.R., Cryer A., Ramji D.P. Differential regulation of lipoprotein lipase in the macrophage J774.2 cell line by cytokines. Cytokine,1996, 8 (7),525-533
19. Wu Z, Bucher NL, Farmer SR. Induction of peroxisome proliferator-activated receptor gamma during the conversion of 3T3 preadipocytes into adipocytes is mediated by C/EBP beta, C/EBP delta and glucocorticoids. Mol Cell Biol,1996,16: 4128-4136
20. Chawla, A., M. A. Lazar. Peroxisome proliferator and retinoid signaling pathways co-regulate preadipocyte pheonotype and survival. Proc. Natl. Acad. Sci. USA 1994, 91:1786-1790
21. Spiegelman BM, Farmer SR. Decreases in tubulin and actin gene expression prior to orphological differentiation of 3T3 adipocytes. Cell,1982,29:53-60
22. Spiegelman, B. M., H. Green. Cyclic AMP-mediated control of lipogenic enzyme synthesis during adipose differentiation of 3T3 cells. Cell 1981,24:503-510
23. Paulauskis J. D., H. S. SUL. Cloning and expression of mouse fatty acid synthase and other specific mRNAs. Developmental and hormonal regulation in 3T3-L1 cells. J Biol Chem.1988,263:7049-7054
24. Weiner, F. R., P. J. Smith, S. Wertheimer, C. S. Rubin. Regulation of gene expression by insulin and tumor necrosis factor alpha in 3T3-L1 cells. Modulation of the transcription of genes encoding acyl-CoA synthetase and stearoyl-CoA esaturase-1. J. Biol. Chem.1991,266:23525-23528
25. Alessi, M. C., F. Peiretti, P. Morange, M. Henry, G. Nalbone, I. Juhan-Vague. Production of plasminogen activator inhibitor 1 by human adipose tissue:possible link between visceral fat accumulation and vascular disease. Diabetes 46:860-867, 1997
26. Choy, L. N., B. M. Spiegelman. Regulation of alternative pathway activation and C3a production by adipose cells. Obesity Res.4:521-532,1996
27. Dobson, D. E, A. Kambe, E. Block, T. Dion, H. Lu, J. Castellot JR, B. M. Spiegelman. 1-Butyryl-glycerol:a novel angiogenesis factor secreted by differentiating adipocytes. Cell 61:223-230,1990
28. Jones, B. H., M. K. Standridge, N. Moustaid. Angiotensin Ⅱ increases lipogenesis in 3T3-L1 and human adipose cells. Endocrinology 138:1512-1519,1997
29. Ziouzenkova O, Orasanu G, Sukhova G et al. Asymmetric Cleavage of Beta-Carotene Yields a Transcriptional Repressor of Retinoid X Receptor and Peroxisome Proliferator-activated Receptor Responses [J]. Molecular Endocrinology,2007,21(1): 77-88
30. Green S. PPAR:A Mediator of Peroxisome Proliferator action [J]. Mutation Research, 1995,333(1-2):101-109
31. Akiyama TE, Lambert G, Nico C.J et al. Peroxisome Proliferator-activated Preceptor Beta/delta Regulates very Low Density Lipoprotein Production and Catabolism in Mice on a Western Diet [J]. J Biol Chem,2004,279(20):20874-20881
32. Grimaldi PA. The Roles of PPARs in Adipocyte Differentiation [J]. Progress Lipid Research,2001,40(4):269-281
33. Schoonjans K, Staels B, Auwers J. The peroxisome proliferator activated receptor and their effects on lipid metabolism and adipocyte differentiation. Biochem Biophys Acta.1996,1302(2):93-109
34. Saladin R, Fajas L, Dana S, et al. Differential regulation of peroxisome proliferator activated receptor gammal(PPAR-gammal)and PPAR-gamma2 messenger RNA expression in the early stages ofadipogenesis. Cell Growth Differ,1999,10(1):43-44
35. Tontonoz P, Singer S, Forman B M, et al. Terminal Differentiation of Human Liposarcoma Cells Induced by Ligands for Peroxisome Proliferator-aetivated Receptor Gamma and the Retinoid X Receptor [J]. Proc Nati Aca Sci USA,1997, 94(1):237-241
36. Madsen L, Petersen R K, Sorensen M B, et al. Adipocyte Differentiation of 3T3-L1 Preadipocytes is Dependent on Lipoxygenase Activity During the Initial Stages of the Differentiation Process [J]. Biochemical Journal,2003,375(3):539-549
37. Rosen ED, Sarraf AE, Troy G, et al. PPAR gamma is required for the differentiation of adipose tissue in vivo and in vitro. Mol Cell,1999,4:611-617
38. Wright HM, Clish CB, Spiegelman BM. A synthetic antagonist for the peroxisome proliferator-activated gamma ligand inhibits adipocyte differentiation. J Biol Chem,2000,275:1873-1877
39. Barroso IM, Gurnell VE, ORahilly S. Dominant negative mutations in human PPAR. gamma associated with severe insulin resistance, diabetes mellitus and hypertension. Nature,1999,402:880-883
40. Diehl AM, Michaelson P, Yang SQ. Selective Induction of CCAAT/enhancer Binding Protein Isoforms Occurs During Rat Liver Development [J]. Gastroenterology,1994, 106(6):1625-1637
41. Li X, Huang HY, Chen JG, et al. Lactacystin Inhibits 3T3-L1 Adipoeyte Differentiation through Induction of CHOP-10 expression [J]. Biochemical and Biophysical Research Communications,2006,350(1):1-6
42. Yeh WC, Cao Z, Mcknight SL. Cascade regulation of terminal adipocyte differentiation by three members of the C/EBP family of leucine zipper proteins. Genes&Dev,1995,15:168-181
43. Tanaka T, Yoshida N, Akira S. Defective adipocyte differentiation in mice lacking the C/EBPβ and/or C/EBPδ gene. EMBO J,1997,16:7432-7443
44. Cheung K J, Tzameli I, Pissios et al. Xanthine Oxidoreductase is a Regulator of Adipogenesis and PPARgamma Activity [J]. Cel Meta,2007,5(2):115-128
45. Choe S S, Choi A H, Lee J W et al. Chronic Activation of Liver X Receptor Induces β-cell Apoptosis Through Hyperactivation of Lipogenesis [J]. Diabetes,2007,56(6): 1534-1543
46. Lord E, Murphy B D, Desmarais J A, et al. Modulation of Peroxisome Proliferator-activated Receptor delta and Gamma Transcripts in Swine Endometrial Tissue During Early Gestation [J]. Reproduction,2006,131(5):929-942
47. Castro M F, Beltran L A, Kuri H W, el al. Commitment of 3T3-F442A Cell to Adipocyte Differentiation Takes Place During the First 24-36h after Adipogenic Stimulation:TNF-alpha inhibits commitmen [J]. Exp Cell Res,2003,2284(2): 163-172
48. Daya S, Loughlin A J, Macqueen H A. Culture and Differentiation of Preadipocytes in Two dimensional and Three-dimensional in Vitro Systems [J]. Exp Cell Res,2007, 75(5):360-370
49. Wang Y, Kim K A, Kim J H, et al. Pref-1, a Preadipocyte Secreted Factor that Inhibits Adipogenesis [J]. J Nutr,2006,136(12):2953-2956
50. LI S X, SONG H D. The Function of Pref-1 in Adipocyte Differentiation [J]. Intl Journal of Endo Met,2006,26(1):41-43
51. Macdougald OA, Lane MD. Transcriptional regulation of gene expression during adipocyte differentiation [J]. Annu Rev Biochem,1995,64:345-373
52. Kim CS, Kawada T, Kwon BS, et al. Macrophage inflammatory protein related protein-2, a novel CC chemokine, can regulate preadipocyte migration and adipocyte differentiation [J]. FEBS Lett,2003,548(1-3):125-130
53. Schmidt M, Park BH, Davis, et al. Adipose conversion of 3T3-L1 cells in a serum free culture system depends on epidermal growth factor, insulin-like growth factor, corticosterone and cyclic AMP [J]. J Biol Chem,1990,165:15489-15495
54. Kim S,Whelan J, Clyacombe K, et al. Angiotensin Ⅱ Increases Leptin Secretion by 3T3-L1 and Human Adipocytes Via a Prostaglandin-independent Mechanism [J]. Journal of Nutrition,2002,132(6):1135-1140
55. Wheatcroft S B, Keamey M T, Shah A M, et al. IGF-binding protein-2 protects against the development d obesity and insulin resistance [J]. Diabetes.2007,56(2): 285-294
56. Zhang H, Noohr J, Jensen C H, et al. Insulin-like Growth factor-1/insulin Bypasses Pref-1/FAl-mediated Inhibition of Adipocyte Differentiation [J]. J Biol logical Chem, 2003,278(23):20906-20914
57. Rosen C J, Ackert-Bicknell C L, Adamo M L. Congenic Mice with Low Serum IGF-1 have Increased Body Fat, Reduced Bone Mineral Density, and an Altered Osteoblast Differentiation Program [J]. Bone,2004,35(5):1046-1058
58. Negrel R, Kim JB, Wright HM, et al. Prostacyclin as a potent effector of adipose-cell differentiation [J]. Biochem J,1989,257:399
59. Vassaux G et al. Differential response of preadipocytes and adipocytes to prostacyclin and prostaglandin E2:Physiological implications [J]. Endocrinology,1992,131:2393
60. Smas CM, Chen I, Zhao L, et al. Transcriptional repression of pref-1 by glucocorticoid promotes 3T3-L1 adipocyte differentiation [J]. J Biol Chem,1999, 274(6):12632-12641