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. 1992 Oct;90(4):1226–1231. doi: 10.1172/JCI115984

Augmented production of heparin-binding mitogenic proteins by preadipocytes from massively obese persons.

K Teichert-Kuliszewska 1, B S Hamilton 1, M Deitel 1, D A Roncari 1
PMCID: PMC443163  PMID: 1401060

Abstract

Basic fibroblast growth factor (bFGF) stimulates the replication of preadipocytes and inhibits their differentiation. In this study we explored whether the same or related polypeptides were produced locally and acted by paracrine/autocrine mechanisms in adipose tissue. Omental preadipocytes from 7 lean and 10 massively obese (> 170% reference) subjects were grown to confluence in subculture. Total RNA was hybridized with a synthetic deoxynucleotide for human bFGF. In the case of all cell strains, there was expression of two major bFGF transcripts, 7.0 and 3.7 kb. Although there was considerable variation in the degree of expression, preadipocytes from massively obese subjects revealed much greater expression than did cells from the lean (P < 0.001). In studies of conditioned media prepared with preadipocytes, the presence of proteins belonging to the heparin-binding (fibroblast) growth factor family was indicated by Western blot analysis, for a 66-kD protein with anti-(1-24)bFGF, and for a 32-kD protein with anti-(40-63)bFGF antibodies. The relative quantity of the 66-kD protein correlated with body mass index at r = 0.72. bFGF-related proteins probably function normally to maintain an appropriate complement of adipocyte precursors. The augmented expression of heparin-binding growth factors in preadipocytes from some massively obese people probably contributes to the excessive cellularity of their fat depots.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Baird A., Esch F., Mormède P., Ueno N., Ling N., Böhlen P., Ying S. Y., Wehrenberg W. B., Guillemin R. Molecular characterization of fibroblast growth factor: distribution and biological activities in various tissues. Recent Prog Horm Res. 1986;42:143–205. doi: 10.1016/b978-0-12-571142-5.50008-2. [DOI] [PubMed] [Google Scholar]
  2. Baird A., Ling N. Fibroblast growth factors are present in the extracellular matrix produced by endothelial cells in vitro: implications for a role of heparinase-like enzymes in the neovascular response. Biochem Biophys Res Commun. 1987 Jan 30;142(2):428–435. doi: 10.1016/0006-291x(87)90292-0. [DOI] [PubMed] [Google Scholar]
  3. Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1006/abio.1976.9999. [DOI] [PubMed] [Google Scholar]
  4. Burgess W. H., Maciag T. The heparin-binding (fibroblast) growth factor family of proteins. Annu Rev Biochem. 1989;58:575–606. doi: 10.1146/annurev.bi.58.070189.003043. [DOI] [PubMed] [Google Scholar]
  5. Casscells W., Speir E., Sasse J., Klagsbrun M., Allen P., Lee M., Calvo B., Chiba M., Haggroth L., Folkman J. Isolation, characterization, and localization of heparin-binding growth factors in the heart. J Clin Invest. 1990 Feb;85(2):433–441. doi: 10.1172/JCI114456. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  7. Folkman J., Klagsbrun M. Angiogenic factors. Science. 1987 Jan 23;235(4787):442–447. doi: 10.1126/science.2432664. [DOI] [PubMed] [Google Scholar]
  8. James R., Bradshaw R. A. Polypeptide growth factors. Annu Rev Biochem. 1984;53:259–292. doi: 10.1146/annurev.bi.53.070184.001355. [DOI] [PubMed] [Google Scholar]
  9. Kardami E., Fandrich R. R. Basic fibroblast growth factor in atria and ventricles of the vertebrate heart. J Cell Biol. 1989 Oct;109(4 Pt 1):1865–1875. doi: 10.1083/jcb.109.4.1865. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  11. Lau D. C., Roncari D. A., Hollenberg C. H. Release of mitogenic factors by cultured preadipocytes from massively obese human subjects. J Clin Invest. 1987 Feb;79(2):632–636. doi: 10.1172/JCI112859. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Lau D. C., Roncari D. A., Yip D. K., Kindler S., Nilsen S. G. Purification of a pituitary polypeptide that stimulates the replication of adipocyte precursors in culture. FEBS Lett. 1983 Mar 21;153(2):395–398. doi: 10.1016/0014-5793(83)80651-6. [DOI] [PubMed] [Google Scholar]
  13. Lau D. C., Shillabeer G., Wong K. L., Tough S. C., Russell J. C. Influence of paracrine factors on preadipocyte replication and differentiation. Int J Obes. 1990;14 (Suppl 3):193–201. [PubMed] [Google Scholar]
  14. Le Blanc P. E., Roncari D. A., Hoar D. I., Adachi A. M. Exaggerated triglyceride accretion in human preadipocyte-murine renal line hybrids composed of cells from massively obese subjects. J Clin Invest. 1988 May;81(5):1639–1645. doi: 10.1172/JCI113499. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Lindner V., Majack R. A., Reidy M. A. Basic fibroblast growth factor stimulates endothelial regrowth and proliferation in denuded arteries. J Clin Invest. 1990 Jun;85(6):2004–2008. doi: 10.1172/JCI114665. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Liu L. M., Nicoll C. S. Evidence for a role of basic fibroblast growth factor in rat embryonic growth and differentiation. Endocrinology. 1988 Oct;123(4):2027–2031. doi: 10.1210/endo-123-4-2027. [DOI] [PubMed] [Google Scholar]
  17. Morrow N. G., Kraus W. E., Moore J. W., Williams R. S., Swain J. L. Increased expression of fibroblast growth factors in a rabbit skeletal muscle model of exercise conditioning. J Clin Invest. 1990 Jun;85(6):1816–1820. doi: 10.1172/JCI114640. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Moscatelli D., Presta M., Joseph-Silverstein J., Rifkin D. B. Both normal and tumor cells produce basic fibroblast growth factor. J Cell Physiol. 1986 Nov;129(2):273–276. doi: 10.1002/jcp.1041290220. [DOI] [PubMed] [Google Scholar]
  19. Murphy P. R., Sato R., Sato Y., Friesen H. G. Fibroblast growth factor messenger ribonucleic acid expression in a human astrocytoma cell line: regulation by serum and cell density. Mol Endocrinol. 1988 Jul;2(7):591–598. doi: 10.1210/mend-2-7-591. [DOI] [PubMed] [Google Scholar]
  20. Navre M., Ringold G. M. A growth factor-repressible gene associated with protein kinase C-mediated inhibition of adipocyte differentiation. J Cell Biol. 1988 Jul;107(1):279–286. doi: 10.1083/jcb.107.1.279. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Rifkin D. B., Moscatelli D. Recent developments in the cell biology of basic fibroblast growth factor. J Cell Biol. 1989 Jul;109(1):1–6. doi: 10.1083/jcb.109.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Riss T. L., Sirbasku D. A. Characterization of polyclonal antibodies that distinguish acidic and basic fibroblast growth factors by using western immunoblotting and enzyme-linked immunosorbent assays. J Cell Physiol. 1989 Feb;138(2):405–414. doi: 10.1002/jcp.1041380224. [DOI] [PubMed] [Google Scholar]
  23. Roncari D. A. Abnormalities of adipose cells in massive obesity. Int J Obes. 1990;14 (Suppl 3):187–192. [PubMed] [Google Scholar]
  24. Roncari D. A. Hormonal influences on the replication and maturation of adipocyte precursors. Int J Obes. 1981;5(6):547–552. [PubMed] [Google Scholar]
  25. Roncari D. A., Kindler S., Hollenberg C. H. Excessive proliferation in culture of reverted adipocytes from massively obese persons. Metabolism. 1986 Jan;35(1):1–4. doi: 10.1016/0026-0495(86)90087-9. [DOI] [PubMed] [Google Scholar]
  26. Roncari D. A., Lau D. C., Kindler S. Exaggerated replication in culture of adipocyte precursors from massively obese persons. Metabolism. 1981 May;30(5):425–427. doi: 10.1016/0026-0495(81)90174-8. [DOI] [PubMed] [Google Scholar]
  27. Roncari D. A., Le Blanc P. E. Inhibition of rat perirenal preadipocyte differentiation. Biochem Cell Biol. 1990 Jan;68(1):238–242. doi: 10.1139/o90-032. [DOI] [PubMed] [Google Scholar]
  28. Spizz G., Roman D., Strauss A., Olson E. N. Serum and fibroblast growth factor inhibit myogenic differentiation through a mechanism dependent on protein synthesis and independent of cell proliferation. J Biol Chem. 1986 Jul 15;261(20):9483–9488. [PubMed] [Google Scholar]
  29. Van R. L., Bayliss C. E., Roncari D. A. Cytological and enzymological characterization of adult human adipocyte precursors in culture. J Clin Invest. 1976 Sep;58(3):699–704. doi: 10.1172/JCI108516. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Van R. L., Roncari D. A. Isolation of fat cell precursors from adult rat adipose tissue. Cell Tissue Res. 1977 Jul 11;181(2):197–203. doi: 10.1007/BF00219980. [DOI] [PubMed] [Google Scholar]
  31. Yayon A., Klagsbrun M. Autocrine regulation of cell growth and transformation by basic fibroblast growth factor. Cancer Metastasis Rev. 1990 Nov;9(3):191–202. doi: 10.1007/BF00046360. [DOI] [PubMed] [Google Scholar]

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