Adipocyte-Related Genes and Transcription Factors were Affected by siRNA for Aromatase Gene during 3T3-L1 Differentiation

지방세포 분화중인 3T3-L1 세포에서 아로마테이즈 siRNA 처리에 의한 지방관련 유전자와 전사인자의 발현 조절

  • Jeong, Dong-Kee (Department of Animal Biotechnology, College of Applied Biosciences, Cheju National University, The Institute of Subtropical Biological Science)
  • 정동기 (제주대학교 생명자원과학대학 생명공학부 동물생명공학, 아열대생명과학 연구소)
  • Published : 2008.11.30


This study was performed to verify the gene expression of 3T3-L1 using the siRNA of the aromatase gene, which is the estrogen synthesis enzymes. First of all three pairs of siRNA were designed from the CYP19A1 (aromatase) and analyzed the formation of fat cell mechanism by transferring gene to 3T3-L1 and differentiating it. As a result, the expression of leptin gene, which is the main gene causing the obesity, was controlled and the cause of the obesity is related with the insulin specifically. The overexpression of adiponectin and adipsin was observed. This result showed that the formation of the fat was controlled a little without any side effect by obstructing a specific material out of all the signal systems in the fat formation. This study will be an important clue to make it clear that the lack or overexpression of estrogen might be the cause of fat formation mechanism.


  1. Bouchard, C., J. P. Despres and P. Mauriege. 1992. Genetic and nongenetic determinants of regional fat distribution. Endocr. Rev. 14, 72-93.
  2. Carani, C., K. Qin, M. Simoni, M. Faustini-Fustini, S. Serpente, J. Boyd, K. Korach and E. R. Simpson. 1997. Effect of testosterone and estradiol in a man with aromatase deficiency. N. Engl. J. Med. 337, 91-95.
  3. De Rodder, C. M., P. F. Brunung, M. L. Zonderland, J. H. Thijssen, J. M. Bonfrer, M. A. Blankenstein, I. A. Huisveld and W. B. Erich. 1990. Body fat mass, body fat distribution, and plasma hormones in early puberty in famales. J. Clin. Endocrinol. Metab. 70, 888-893.
  4. Elbers, J. M. H., H. Asscheman, J. C. Seidell and L. J. G. Gooren. 1999. Effects of sex steroid hormones on regional fat depots as assessed by magnetic resonance imaging in transsexuals. Am. J. Physiol. 276, E317-E325.
  5. Fasshauer, M. and R. Paschke. 2003. Regulation of adipocytokines and insulin resistance. Diabetologia. 46, 1594-1603.
  6. Gambacciani, M., M. Ciaponi, B. Cappagli, L. Piaggesi, L. De Simone, R. Orlandi and A. R. Genazzani. 1997. Body weight, body fat distribution, and hormonal replacement therapy in early postmenopausal women. J. Clin. Endocrinol. Metab. 82, 414-417.
  7. Haarbo, J., U. Marslew, A. Gotfredsen and C. Christiansen. 1991. Postmenopausal hormone replacement therapy prevents central distribution of body fat after menopause. Metab. 40, 1323-1326.
  8. Harada, N. 1988. Novel properties of human placental aromatase as cytochrome P-450: Purification and characterization of a unique form of aromatase. J. Biochem. 103, 106-113.
  9. Heine, P. A., J. A. Taylor, G. A. Iwamoto, D. B. Lubahn and P. S. Cooke. 2000. Increased adipose tissue in male and female estrogen receptor-a knockout mice. Proc. Natl. Acad. Sci. 97, 12729-12734.
  10. Jiang, Z. Y., Q. L. Zhou, K. A. Coleman, M. Chouinard, Q. Boese and M. P. Czech. 2003. Insulin signaling through Akt/protein kinase B analyzed by small interfering RNA-mediated gene silencing. Proc. Natl. Acad. Sci. 100, 7569-7574.
  11. Jones, M. E., A. W. Thorburn, K. L. Britt, K. N. Hewitt, N. G. Wreford, J. Proietto, O. K. Oz, B. J. Leuryi, K. M. Robertson, S. Yao and E. R. Simpson. 2000. Aromatase-deficient (ArKO) mice have a phenotype of increased adiposity. Proc. Natl. Acad. Sci. 97, 12735-12740.
  12. Jones, M. E., A. W. Thorburn, K. L. Britt, K. N. Hewitt, M. L. Misso, N. G. Wreford, J. Proietto, O. K. Oz, B. J. Leury, K. M. Robertson, S. Yao and E. R. Simpson. 2001. Aromatase-deficient (ArKO) mice accumulate excess adipose tissue. J. Steroid. Biochem. Mol. Biol. 79, 3-9.
  13. Kadowaki, T. and T. Yamauchi. 2005. Adiponectin and adiponectin receptors. Endocrine Rev. 26, 439-451.
  14. Lemieux, S., D. Prud'homme, C. Bouchard, A. Tremblay and J. P. Despres. 1993. Sex differences in the relation of visceral adipose tissue accumulation to total body fatness. Am. J. Clin. Nutr. 58, 463-467.
  15. Liao, W., M. T. Audrey Nguyen, T. Imamura, O. Singer, I. M. Verma and J. M. Olefsky. 2006. Lentiviral short hairpin ribonucleic acid-mediated knockdown of GLUT4 in 3T3-L1 adipocytes. Endocrinol. 147, 2245-2252.
  16. Madsen, L., K. Rasmus, M. Petersen, B. Sorensen, C. Jorgensen, P. Hallenborg, L. Pridal, J. Fleckner, E. Amri II, P. Krieg, G. Furstenberger, R. K. Berge and K. Kristiansen. 2003. Adipocyte differentiation of 3T3-L1 preadipocytes is dependent on lipoxygenase activity during the initial stages of the differentiation process. Biochem. J. 375, 539-549.
  17. Mitra, P., X. Zheng and M. P. Czech. 2004. RNAi-based analysis of CAP, Cbl, and CrkII function in the regulation of GLUT4 by Insulin. J. Biol. Chem. 279, 37431-37435.
  18. Morishima, A., M. M. Grumbach, E. R. Simpson, C. Fisher and K. Qin. 1995. Aromatase deficiency in male and female siblings caused by a novel mutation and the physiological role of estrogens. J. Clin. Endocrinol. Metab. 80, 3689-3698.
  19. Nguyen, M. T., H. Satoh, S. Favelyukis, J. L. Babendure, T. Imamura, J. l. Sbodio, J. Zalevsky, B. I. Dahiyat, N. W. Chi and J. M. Olefsky. 2005. JNK and tumor necrosis factor-mediate free fatty acid-induced insulin resistance in 3T3-L1 adipocytes. J. Biol. Chem. 280, 35361-35371.
  20. Simpson, E. R., G. Rubin, C. Clyne, K. Robertson, L. O Donnell, M. Jones and S. Davis. 2000. The role of local estrogen biosynthesis in males and females. Trends in Endocrinol. and Metab. 11, 184-188.
  21. Trigatti, B., H. Rayburn, M. Vinals, A. Braun, H. Miettinen, M. Penman, M. Hertz, M. Schrenzel, L. Amigo, A. Rigotti and M. Krieger. 1999. Influence of the high density lipoprotein receptor SR-BI on reproductive and cardiovascular pathophysiology. Proc. Natl. Acad. Sci. 96, 9322-9327.
  22. Wade, G. N. 1972. Gonadal hormones and behavioral regulation of body weight. Physiol Behav. 8, 523-534.