Skip to main content
SpringerLink
Log in

Regulation of transcription factor mRNA accumulation during 3T3-L1 preadipocyte differentiation by antagonists of adipogenesis

  • Chapter
Cellular Fatty Acid-Binding Proteins II

Part of the book series: Developments in Molecular and Cellular Biochemistry ((DMCB,volume 10))

  • 67 Accesses

Abstract

3T3-L1 preadipocytes differentiate into cells having the biochemical properties of adipocytes; tumor necrosis factor-α (TNF), retinoic acid (RA), and transforming growth factor-β (TGF-β), attenuate this process. Inhibition of differentiation by these agents, thought to be at the level of transcription, has been investigated by examining the accumulation of mRNA for six transcription factors and the autocrine growth factor interleukin 6 (IL-6). Upon induction of differentiation, a rapid and major accumulation of c-fos and jun-B mRNA was observed that returned to near basal levels within 4–6 h. In contrast, c-jun mRNA, although rapidly expressed following induction of differentiation, remained at relatively constant levels throughout the time course. Exposure of the cells to 5 nM TNF potentiated the accumulation of all 3 mRNAs but most significantly c-jun (12-fold), which remained elevated for at least 24 h after treatment. In control differentiating cells, krox-20 and fox-B were expressed transiently, 30 min to 2 h, while fra-1 mRNA accumulated over an extended period, 1 to 8 h. Again, TNF enhanced the accumulation of these mRNAs. Accumulation of mRNA for C/EBP, a transcription factor proposed to control expression of genes involved in the terminally differentiated state was attenuated after exposure of the cells to TNF. C/EBP expression was also inhibited in cells exposed to RA or TGF-β. IL-6 mRNA was expressed briefly (30 min to 2 h) and again transiently (at 8 h after induction of differentiation). TNF treatment markedly enhanced accumulation of IL-6 message. We propose that increased cellular content of one or more transcription factors or the suppression of C/EBP may be responsible for the attenuation of differentiation induced by exposure of the cells to TNF, RA, and TGF-β.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Green H, Kehinde O: Sublines of mouse 3T3 cells that accumulate lipid. Cell 1: 113–116, 1974

    Article  CAS  Google Scholar 

  2. Green H, Kehinde O: Spontaneous heritable changes leading to increased adipose conversion in 3T3 cells. Cell 7: 105–113, 1976

    Article  PubMed  CAS  Google Scholar 

  3. Green H, Kehinde O: Formation of normally differentiated subcutaneous fat pads by an established preadipose cell line. J Cell Physiol 101: 169–172, 1979

    Article  PubMed  CAS  Google Scholar 

  4. Rubin CS, Lai E, Rosen OM: Acquisition of increased hormone sensitivity during in vitro adipocyte development. J Biol Chem 252: 3554–3557, 1977

    PubMed  CAS  Google Scholar 

  5. Karlsson FA, Grunfeld C, Kahn CR, Roth J: Regulation of insulin receptor and insulin responsiveness in 3T3-L1 fatty fibroblasts. Endocrinology 104:1383–1392, 1979

    Article  PubMed  CAS  Google Scholar 

  6. Reed B, Lane MD: Insulin receptor synthesis and turnover in differentiating 3T3-L1 preadipocytes. Proc Natl Acad Sci USA 77: 285–289, 1980

    Article  PubMed  CAS  Google Scholar 

  7. Mackall JC, Lane MD: Role of pyruvate carboxylase in fatty acid synthesis: alterations during preadipocyte differentiation. Bio-chem Biophys Res Commun 79: 720–725, 1977

    Article  CAS  Google Scholar 

  8. Wise LS, Green H: Studies of lipoprotein lipase during the adipose conversion of 3T3 cells. Cell 13: 233–242, 1978

    Article  PubMed  CAS  Google Scholar 

  9. Spooner PM, Chernick SS, Garrison MM, Scow RO: Insulin regulation of lipoprotein lipase activity and release in 3T3-L1 adipocytes. J Biol Chem 254:10021–10029, 1979

    PubMed  CAS  Google Scholar 

  10. Spiegelman BM, Farmer SR: Decreases in tubulin and actin gene expression prior to morphological differentiation of 3T3 adipocytes. Cell 29: 53–60, 1982

    Article  PubMed  CAS  Google Scholar 

  11. Bernlohr DA, Bolanowski MA, Kelly TJ, Lane MD: Evidence for an increase in transcription of specific mRNAs during differentiation of 3T3-L1 preadipocytes. J Biol Chem 260: 5563–5567, 1985

    PubMed  CAS  Google Scholar 

  12. Cook KS, Hunt CR, Spiegelman BM: Developmentally regulated mRNAs in 3T3-L1 adipocytes: analysis of transcriptional control. J Cell Biol 100: 514–520, 1985

    Article  PubMed  CAS  Google Scholar 

  13. Dijan P, Phillips M, Green H: The activity of specific gene transcription in the adipose conversion of 3T3 cells. J Cell Physiol 124: 554–556, 1985

    Article  Google Scholar 

  14. Herrera R, Ro HS, Robinson GS, Xanthopolous KO, Spiegelman BM: A direct role for C/EBP and the AP-1 binding site in gene expression linked to adipocyte differentiation. Mol Cell Biol 9: 5331–5339, 1989

    PubMed  CAS  Google Scholar 

  15. Christy RJ, Yang VW, Natambi JM, Geiman DE, Landschulz WH, Friedman AD, Nakabeppu U, Kelly TJ, Lane MD: Differentiation-induced gene expression in 3T3-L1 preadipocytes: CCAAT/enhancer binding protein interacts with and activates the promoters of two adipocyte-specific genes. Genes & Development 3:1323–1335, 1989

    Article  CAS  Google Scholar 

  16. Distel RJ, Ro JH-S, Rasen BS, Groves DL, Spiegelman BM: Nu-cleoprotein complexes that regulate gene expression in adipocyte differentiation: direct participation of c-fos. Cell 49:835–844, 1987

    Article  PubMed  CAS  Google Scholar 

  17. Yang VW, Christy RJ, Cook JS, Kelly TJ, Lane MD: Mechanism of regulation of the 422(aP2) gene by cAMP during preadipocyte differentiation. Proc Natl Acad Sci USA 86: 3629–3633,1989

    Article  PubMed  CAS  Google Scholar 

  18. Ntambi JM, Buhrow SA, Kaestner KH, Christy RJ, Sibley E, Kelly TJ, Lane MD: Differentiation-induced gene expression in 3T3-L1 preadipocytes. J Biol Chem 262:17291–17300, 1988

    Google Scholar 

  19. Kaestner KH, McLenithan JC, Christy R, Braireiman LT, Cornelius PC, Pekala PH, Lane MD: Sequence, tissue distribution, and differential expression of mRNA for a putative insulin-responsive glucose transporter in mouse 3T3-L1 adipocytes. Proc Natl Acad Sci USA 86: 3150–3154, 1989

    Article  PubMed  CAS  Google Scholar 

  20. Cook JS, Lucas JJ, Sibley E, Bolanowski MA, Christy RJ, Kelly TJ, Lane MD: Expression of the differentiation-induced gene for fatty acid-binding protein is activated by glucorticoids and cAMP Proc Natl Acad Sci USA 85: 2949–2953, 1988

    Article  PubMed  CAS  Google Scholar 

  21. Kaestner KH, Christy RJ, Lane MD: Mouse insulin-responsive glucose transporter gene: characterization of the gene and trans-activation by the CCAAT/enhancer binding protein. Proc Natl Sci USA 87: 251–255, 1990

    Article  CAS  Google Scholar 

  22. McKnight SL, Lane MD, Gluecksohn-Waelsch S: Is CCAAT/en-hancer-binding protein a central regulator of energy metabolism? Genes & Development 3: 2021–2024, 1989

    Article  CAS  Google Scholar 

  23. Old LJ: Tumor necrosis factor. Science 230: 630–632, 1985

    Article  PubMed  CAS  Google Scholar 

  24. Beutler B, Cerami A: Tumor necrosis factor and cachectin: two sides of the same biological coin. Nature 320: 584–588, 1986

    Article  PubMed  CAS  Google Scholar 

  25. Nathan CF: Secretory products of macrophages. J Clin Invest 79: 319–326, 1987

    Article  PubMed  CAS  Google Scholar 

  26. Carswell Å, Old LJ, Kassel RL, Green S, Fiore N, Williamson B: Proc Natl Acad Sci USA 72: 3666–3670, 1975

    Article  PubMed  CAS  Google Scholar 

  27. Helson L, Green S, Carswell EÅ, Old LJ: Effect of tumour necrosis factor on cultured human melanoma cells. Nature 258:13655–13662

    Google Scholar 

  28. Kull FC, Cuatrecasas P: Necrosin: purification and properties of a cyotoxin derived from a murine macrophage-like cell line. Proc Natl Acad Sci USA 81: 7932–7936, 1984

    Article  PubMed  CAS  Google Scholar 

  29. Sugarman BJ, Aggarwal BB, Hass PE, Ϊigari IS, Palladino M, She-pard HM: Recombinant human tumor necrosis factor-α: effects on proliferation of normal and transformed cells in vitro. Science 230: 943–945, 1985

    Article  PubMed  CAS  Google Scholar 

  30. Vilcek J, Palombella V, Henrikson-De Stefano D, Swenson C, Feinman R, Hirai M, Tsujimoto M: Fibroblasts growth enhancing activity of tumor necrosis factor and its relationship to other polypeptide growth factors. J Exp Med 163: 632–643, 1986

    Article  PubMed  CAS  Google Scholar 

  31. Cornelius P, Enerback S, Bjursell Olivecrona T, Pekala PH: Regulation of lipoprotein lipase mRNA content in 3T3-L1 cells by tumour necrosis factor. Biochem J 249: 765–769, 1988

    PubMed  CAS  Google Scholar 

  32. Pekala PH, Marlowe M, Heuvelman D, Connolly D: Regulation of hexose transport in aortic endothelial cells by VPF and TNF-α, but not by insulin, J Biol Chem 265:18051–18054, 1990

    PubMed  CAS  Google Scholar 

  33. Cornelius P, Lee MD, Marlowe M, Pekala PH: The growth factorlike effects of tumor necrosis factor-α. J Biol Chem 265: 20606–20516

    Google Scholar 

  34. Brenner DA, O’Hara M, Angel P, Chojkier M, Karin M: Prolonged activation of jun and collagenase genes by tumour necrosis factor-α. Nature 337: 661–663, 1988

    Article  Google Scholar 

  35. Lin J-X, Vilcek J: Tumor necrosis factor and interleukin-1 cause a rapid and transient stimulation of c-fos and c-myc mRNA levels in human fibroblasts. J Biol Chem 262:11908–11911, 1987

    PubMed  CAS  Google Scholar 

  36. Torti FÂ, Dieckmann B, Beutler B, Cerami A, Ringold G: A macrophage factor inhibits adipocyte gene expression: an in vitro model of cachexia. Science 229: 867–869, 1985

    Article  PubMed  CAS  Google Scholar 

  37. Torti FM, Torti SV, Larrick JW, Ringold GM: Modulation of adipocyte differentiation by tumor necrosis factor and transforming growth factor beta. J Cell Biol 108:1105–1113, 1989

    Article  PubMed  CAS  Google Scholar 

  38. Stone RL, Bernlohr DA: The role of retinoic acid in 3T3-L1 pre-adipocyte adipose conversion: antagonistic effects of stimulatory and inhibitory factors during differentiation. Differentiation, 45: 119–127, 1990

    Article  PubMed  CAS  Google Scholar 

  39. Curran T, Peters G, Van Beveren C, Teich NM, Verma I: FBJ murine osteosarcoma virus: identification and molecular cloning of biological active proviral DNA. J Virol 44: 674–682, 1982

    PubMed  CAS  Google Scholar 

  40. Cleveland D, Lopala MA, McDonald RJ, Cowan NJ, Rutter WJ, Kirschner MJ: Number and evolutionary conservation of alpha-and beta-tubulin and cytoplasmic beta-and gamma-actin genes using specific cloned cDNA probes. Cell 20: 95–105, 1980

    Article  PubMed  CAS  Google Scholar 

  41. Lamph WW, Wamsley P, Sassone-Corsi P, Verma IM: Induction of proto-oncogene jun/AP-1 by serum and TPA. Nature 334: 629–631, 1988

    Article  PubMed  CAS  Google Scholar 

  42. Ryder K, Lau LF, Nathans D: A gene activated by growth factors is related to the oncogene v-jun. Proc Natl Acad Sci USA 85: 1487–1491, 1988

    Article  PubMed  CAS  Google Scholar 

  43. Van Snick J, Cayphas S, Szikora JP, Renauld JC, Roost EV, Simpson RJ: cDNA cloning of murine interleukin-HP1: homology with human interleukin-6. Eur J Immunol 18:193–197,1988

    Article  PubMed  Google Scholar 

  44. Zerial M, Toschi L, Ryseck R-P, Schuermann M, Muller R, Bravo R: The product of a novel growth factor activated gene, fos B, interacts with jun protein enhancing their DNA binding activity. EMBO J 8: 805–813, 1989

    PubMed  CAS  Google Scholar 

  45. Chavrier P, Janssen-Timmen U, Mattei M-G, Zerial M, Bravo R, Charnay P: Structure, chromosome location and expression of the mouse zinc finger gene krox-20: multiple gene products and co-regulation with the proto-oncogene c-fos. Mol Cell Biol 9: 787–797, 1989

    PubMed  CAS  Google Scholar 

  46. Chiu R, Boyle WJ, Meek J, Smeal T, Hunter T, Karin M: The c-fos protein interacts with c-jun/AP-1 to stimulate transcription of AP-1 responsive genes. Cell 54: 541–552, 1988

    Article  PubMed  CAS  Google Scholar 

  47. Chiu C-P, Moulds C, Coffman RL, Rennick D, Lee F: Multiple biological activities are expressed by a mouse interleukin 6 cDNA clone isolated from bone marrow stromal cells. Proc Natl Acad Sci USA 85: 8099–7103, 1988

    Article  Google Scholar 

  48. Li L, Hu J-S, Olsen EN: Different members of the jun proto-oncogene family exhibit distinct patterns of expression in response to type β transforming growth factor. J Biol Chem 264: 1556–1559, 1990

    Google Scholar 

  49. James PA, Taylor SM: Cellular differentiation, cytidine analogs and DNA methylation. Cell 20: 85–93, 1980

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biochemistry, School of Medicine, East Carolina University, Greenville, NC, 27858, USA

    Jacqueline M. Stephens, Michelle Butts & Philip H. Pekala

  2. Department of Biochemistry, The University of Minnesota, St. Paul, MN, 55108, USA

    Randy Stone

  3. Dept. of Biochemistry, University of Minnesota, 1479 Gortner Ave., St. Paul, MN, 55108, USA

    David A. Bernlohr

Authors
  1. Jacqueline M. Stephens
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michelle Butts
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Randy Stone
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Philip H. Pekala
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. David A. Bernlohr
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Physiology, University of Limburg, Maastricht, The Netherlands

    Jan F. C. Glatz  & Ger J. van der Vusse  & 

Rights and permissions

Reprints and permissions

Copyright information

© 1993 Springer Science+Business Media Dordrecht

About this chapter

Cite this chapter

Stephens, J.M., Butts, M., Stone, R., Pekala, P.H., Bernlohr, D.A. (1993). Regulation of transcription factor mRNA accumulation during 3T3-L1 preadipocyte differentiation by antagonists of adipogenesis. In: Glatz, J.F.C., van der Vusse, G.J. (eds) Cellular Fatty Acid-Binding Proteins II. Developments in Molecular and Cellular Biochemistry, vol 10. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-3096-1_9

Download citation

  • DOI: https://doi.org/10.1007/978-1-4615-3096-1_9

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-6353-8

  • Online ISBN: 978-1-4615-3096-1

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation