PPARs and Adipose Cell Plasticity

Abstract

Due to the importance of fat tissues in both energy balance and in the associated disorders arising when such balance is not maintained, adipocyte differentiation has been extensively investigated in order to control and inhibit the enlargement of white adipose tissue. The ability of a cell to undergo adipocyte differentiation is one particular feature of all mesenchymal cells. Up until now, the peroxysome proliferator-activated receptor (PPAR) subtypes appear to be the keys and essential players capable of inducing and controlling adipocyte differentiation. In addition, it is now accepted that adipose cells present a broad plasticity that allows them to differentiate towards various mesodermal phenotypes. The role of PPARs in such plasticity is reviewed here, although no definite conclusion can yet be drawn. Many questions thus remain open concerning the definition of preadipocytes and the relative importance of PPARs in comparison to other master factors involved in the other mesodermal phenotypes.

References

1. R. Ellenbogen, “Free autogenous pearl fat grafts in the face—a preliminary report of a rediscovered technique,” Annals of Plastic Surgery, vol. 16, no. 3, pp. 179–194, 1986. View at: Google Scholar
2. T. A. Moseley, M. Zhu, and M. H. Hedrick, “Adipose-derived stem and progenitor cells as fillers in plastic and reconstructive surgery,” Plastic and Reconstructive Surgery, vol. 118, no. 3 supplement, pp. 121S–128S, 2006. View at: Publisher Site | Google Scholar
3. M. S. Stosich and J. J. Mao, “Adipose tissue engineering from human adult stem cells: clinical implications in plastic and reconstructive surgery,” Plastic and Reconstructive Surgery, vol. 119, no. 1, pp. 71–83, 2007. View at: Publisher Site | Google Scholar
4. G. Ailhaud, P. Grimaldi, and R. Négrel, “Cellular and molecular aspects of adipose tissue development,” Annual Review of Nutrition, vol. 12, pp. 207–233, 1992. View at: Publisher Site | Google Scholar
5. J. M. Gimble, “The function of adipocytes in the bone marrow stroma,” New Biologist, vol. 2, no. 4, pp. 304–312, 1990. View at: Google Scholar
6. J. Himms-Hagen, “Brown adipose tissue thermogenesis: interdisciplinary studies,” FASEB Journal, vol. 4, no. 11, pp. 2890–2898, 1990. View at: Google Scholar
7. G. Ailhaud, “Adipose tissue as an endocrine organ,” International Journal of Obesity and Related Metabolic Disorders, vol. 24, supplement 2, pp. S1–S3, 2000. View at: Google Scholar
8. S. Klaus, L. Casteilla, F. Bouillaud, and D. Ricquier, “The uncoupling protein UCP: a membraneous mitochondrial ion carrier exclusively expressed in brown adipose tissue,” International Journal of Biochemistry, vol. 23, no. 9, pp. 791–801, 1991. View at: Publisher Site | Google Scholar
9. D. G. Nicholls and R. M. Locke, “Thermogenic mechanisms in brown fat,” Physiological Reviews, vol. 64, no. 1, pp. 1–64, 1984. View at: Google Scholar
10. B. Prunet-Marcassus, B. Cousin, D. Caton, M. André, L. Pénicaud, and L. Casteilla, “From heterogeneity to plasticity in adipose tissues: site-specific differences,” Experimental Cell Research, vol. 312, no. 6, pp. 727–736, 2006. View at: Publisher Site | Google Scholar
11. S. Klaus and J. Keijer, “Gene expression profiling of adipose tissue: individual, depot-dependent, and sex-dependent variabilities,” Nutrition, vol. 20, no. 1, pp. 115–120, 2004. View at: Publisher Site | Google Scholar
12. B. L. Wajchenberg, “Subcutaneous and visceral adipose tissue: their relation to the metabolic syndrome,” Endocrine Reviews, vol. 21, no. 6, pp. 697–738, 2000. View at: Publisher Site | Google Scholar
13. D. L. Mackay, P. J. Tesar, L.-N. Liang, and S. E. Haynesworth, “Characterizing medullary and human mesenchymal stem cell-derived adipocytes,” Journal of Cellular Physiology, vol. 207, no. 3, pp. 722–728, 2006. View at: Publisher Site | Google Scholar
14. S. Altiok, M. Xu, and B. M. Spiegelman, “PPAR$\gamma$ induces cell cycle withdrawal: inhibition of E2f/DP DNA-binding activity via down-regulation of PP2A,” Genes and Development, vol. 11, no. 15, pp. 1987–1998, 1997. View at: Google Scholar
15. L. Fajas, R. L. Landsberg, Y. Huss-Garcia, C. Sardet, J. A. Lees, and J. Auwerx, “E2Fs regulate adipocyte differentiation,” Developmental Cell, vol. 3, no. 1, pp. 39–49, 2002. View at: Publisher Site | Google Scholar
16. M. Classon, B. K. Kennedy, R. Mulloy, and E. Harlow, “Opposing roles of pRB and p107 in adipocyte differentiation,” Proceedings of the National Academy of Sciences of the United States of America, vol. 97, no. 20, pp. 10826–10831, 2000. View at: Publisher Site | Google Scholar
17. P. Tontonoz, S. Singer, and B. M. Forman et al., “Terminal differentiation of human liposarcoma cells induced by ligands for peroxisome proliferator-activated receptor $\gamma$ and the retinoid X receptor,” Proceedings of the National Academy of Sciences of the United States of America, vol. 94, no. 1, pp. 237–241, 1997. View at: Publisher Site | Google Scholar
18. J.-R. Weng, C.-Y. Chen, J. J. Pinzone, M. D. Ringel, and C.-S. Chen, “Beyond peroxisome proliferator-activated receptor $\gamma$ signaling: the multi-facets of the antitumor effect of thiazolidinediones,” Endocrine-Related Cancer, vol. 13, no. 2, pp. 401–413, 2006. View at: Publisher Site | Google Scholar
19. K. Wada, A. Nakajima, and K. Katayama et al., “Peroxisome proliferator-activated receptor $\gamma$-mediated regulation of neural stem cell proliferation and differentiation,” Journal of Biological Chemistry, vol. 281, no. 18, pp. 12673–12681, 2006. View at: Publisher Site | Google Scholar
20. B. M. Spiegelman, “PPAR-$\gamma$: adipogenic regulator and thiazolidinedione receptor,” Diabetes, vol. 47, no. 4, pp. 507–514, 1998. View at: Publisher Site | Google Scholar
21. B. M. Spiegelman, P. Puigserver, and Z. Wu, “Regulation of adipogenesis and energy balance by PPAR$\gamma$ and PGC-1,” International Journal of Obesity and Related Metabolic Disorders, vol. 24, supplement 4, pp. S8–S10, 2000. View at: Google Scholar
22. E. D. Rosen, “The transcriptional basis of adipocyte development,” Prostaglandins Leukotrienes and Essential Fatty Acids, vol. 73, no. 1, pp. 31–34, 2005. View at: Publisher Site | Google Scholar
23. D. Yoshiga, N. Sato, and T. Torisu et al., “Adaptor protein SH2-B linking receptor-tyrosine kinase and Akt promotes adipocyte differentiation by regulating peroxisome proliferator-activated receptor $\gamma$ messenger ribonucleic acid levels,” Molecular Endocrinology, vol. 21, no. 5, pp. 1120–1131, 2007. View at: Publisher Site | Google Scholar
24. A. Fredenrich and P. A. Grimaldi, “PPAR delta: an uncompletely known nuclear receptor,” Diabetes and Metabolism, vol. 31, no. 1, pp. 23–27, 2005. View at: Publisher Site | Google Scholar
25. R. M. Evans, G. D. Barish, and Y.-X. Wang, “PPARs and the complex journey to obesity,” Nature Medicine, vol. 10, no. 4, pp. 355–361, 2004. View at: Publisher Site | Google Scholar
26. M. Carmona, K. Louche, and M. Nibbelink et al., “Fenofibrate prevents Rosiglitazone-induced body weight gain in ob/ob mice,” International Journal of Obesity, vol. 29, no. 7, pp. 864–871, 2005. View at: Publisher Site | Google Scholar
27. P. Li, Z. Zhu, Y. Lu, and J. G. Granneman, “Metabolic and cellular plasticity in white adipose tissue II: role of peroxisome proliferator-activated receptor-$\alpha$,” American Journal of Physiology - Endocrinology and Metabolism, vol. 289, no. 4, pp. E617–E626, 2005. View at: Publisher Site | Google Scholar
28. K. Matsusue, J. M. Peters, and F. J. Gonzalez, “PPAR$\beta /\delta$ potentiates PPAR$\gamma$-stimulated adipocyte differentiation,” FASEB Journal, vol. 18, no. 12, pp. 1477–1479, 2004. View at: Publisher Site | Google Scholar
29. Z. Yun, H. L. Maecker, R. S. Johnson, and A. J. Giaccia, “Inhibition of PPAR$\gamma$2 gene expression by the HIF-1-regulated gene DEC1/Stra13: a mechanism for regulation of adipogenesis by hypoxia,” Developmental Cell, vol. 2, no. 3, pp. 331–341, 2002. View at: Publisher Site | Google Scholar
30. M. Suzawa, I. Takada, and J. Yanagisawa et al., “Cytokines suppress adipogenesis and PPAR-$\gamma$ function through the TAK1/TAB1/NIK cascade,” Nature Cell Biology, vol. 5, no. 3, pp. 224–230, 2003. View at: Publisher Site | Google Scholar
31. Q. Tong, G. Dalgin, H. Xu, C.-N. Ting, J. M. Leiden, and G. S. Hotamisligil, “Function of GATA transcription factors in preadipocyte-adipocyte transition,” Science, vol. 290, no. 5489, pp. 134–138, 2000. View at: Publisher Site | Google Scholar
32. K. M. Hong, M. D. Burdick, R. J. Philips, D. Heber, and R. M. Strieter, “Characterization of human fibrocytes as circulating adipocyte progenitors and the formation of human adipose tissue in SCID mice,” FASEB Journal, vol. 19, no. 14, pp. 2029–2031, 2005. View at: Publisher Site | Google Scholar
33. J. T. Crossno Jr., S. M. Majka, T. Grazia, R. G. Gill, and D. J. Klemm, “Rosiglitazone promotes development of a novel adipocyte population from bone marrow-derived circulating progenitor cells,” Journal of Clinical Investigation, vol. 116, no. 12, pp. 3220–3228, 2006. View at: Publisher Site | Google Scholar
34. B. Cousin, S. Cinti, and M. Morroni et al., “Occurrence of brown adipocytes in rat white adipose tissue: molecular and morphological characterization,” Journal of Cell Science, vol. 103, part 4, pp. 931–942, 1992. View at: Google Scholar
35. N. Viguerie-Bascands, A. Bousquet-Mélou, and J. Galitzky et al., “Evidence for numerous brown adipocytes lacking functional $\beta$ 3-adrenoceptors in fat pads from nonhuman primates,” Journal of Clinical Endocrinology and Metabolism, vol. 81, no. 1, pp. 368–375, 1996. View at: Publisher Site | Google Scholar
36. S. Cinti, “The adipose organ,” Prostaglandins Leukotrienes and Essential Fatty Acids, vol. 73, no. 1, pp. 9–15, 2005. View at: Publisher Site | Google Scholar
37. L. Casteilla, J. Nouguès, Y. Reyne, and D. Ricquier, “Differentiation of ovine brown adipocyte precursor cells in a chemically defined serum-free medium. Importance of glucocorticoids and age of animals,” European Journal of Biochemistry, vol. 198, no. 1, pp. 195–199, 1991. View at: Publisher Site | Google Scholar
38. K. Moulin, N. Truel, and M. André et al., “Emergence during development of the white-adipocyte cell phenotype is independent of the brown-adipocyte cell phenotype,” Biochemical Journal, vol. 356, part 2, pp. 659–664, 2001. View at: Publisher Site | Google Scholar
39. C. Dani, A. G. Smith, and S. Dessolin et al., “Differentiation of embryonic stem cells into adipocytes in vitro,” Journal of Cell Science, vol. 110, part 11, pp. 1279–1285, 1997. View at: Google Scholar
40. A. Valmaseda, M. Carmona, and M. J. Barberá et al., “Opposite regulation of PPAR-$\alpha$ and -$\gamma$ gene expression by both their ligands and retinoic acid in brown adipocytes,” Molecular and Cellular Endocrinology, vol. 154, no. 1-2, pp. 101–109, 1999. View at: Publisher Site | Google Scholar
41. P. Puigserver, Z. Wu, C. W. Park, R. Graves, M. Wright, and B. M. Spiegelman, “A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis,” Cell, vol. 92, no. 6, pp. 829–839, 1998. View at: Publisher Site | Google Scholar
42. C. Tiraby, G. Tavernier, and C. Lefort et al., “Acquirement of brown fat cell features by human white adipocytes,” Journal of Biological Chemistry, vol. 278, no. 35, pp. 33370–33376, 2003. View at: Publisher Site | Google Scholar
43. C. Handschin and B. M. Spiegelman, “Peroxisome proliferator-activated receptor $\gamma$ coactivator 1 coactivators, energy homeostasis, and metabolism,” Endocrine Reviews, vol. 27, no. 7, pp. 728–735, 2006. View at: Publisher Site | Google Scholar
44. J. B. Hansen, C. Jørgensen, and R. K. Petersen et al., “Retinoblastoma protein functions as a molecular switch determining white versus brown adipocyte differentiation,” Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 12, pp. 4112–4117, 2004. View at: Publisher Site | Google Scholar
45. M. Christian, E. Kiskinis, D. Debevec, G. Leonardsson, R. White, and M. G. Parker, “RIP140-targeted repression of gene expression in adipocytes,” Molecular and Cellular Biology, vol. 25, no. 21, pp. 9383–9391, 2005. View at: Publisher Site | Google Scholar
46. L. Casteilla and C. Dani, “Adipose tissue-derived cells: from physiology to regenerative medicine,” Diabetes and Metabolism, vol. 32, no. 5, part 1, pp. 393–401, 2006. View at: Publisher Site | Google Scholar
47. J. M. Gimble and F. Guilak, “Adipose-derived adult stem cells: isolation, characterization, and differentiation potential,” Cytotherapy, vol. 5, no. 5, pp. 362–369, 2003. View at: Publisher Site | Google Scholar
48. P. A. Zuk, M. Zhu, and P. Ashjian et al., “Human adipose tissue is a source of multipotent stem cells,” Molecular Biology of the Cell, vol. 13, no. 12, pp. 4279–4295, 2002. View at: Publisher Site | Google Scholar
49. K. Yamanouchi, A. Ban, S. Shibata, T. Hosoyama, Y. Murakami, and M. Nishihara, “Both PPAR$\gamma$ and C/EBP$\alpha$ are sufficient to induce transdifferentiation of goat fetal myoblasts into adipocytes,” 2007, to appear in Journal of Reproduction and Development. View at: Google Scholar
50. M. F. Pittenger, A. M. Mackay, and S. C. Beck et al., “Multilineage potential of adult human mesenchymal stem cells,” Science, vol. 284, no. 5411, pp. 143–147, 1999. View at: Publisher Site | Google Scholar
51. A.-M. Rodriguez, D. Pisani, and C. A. Dechesne et al., “Transplantation of a multipotent cell population from human adipose tissue induces dystrophin expression in the immunocompetent mdx mouse,” Journal of Experimental Medicine, vol. 201, no. 9, pp. 1397–1405, 2005. View at: Publisher Site | Google Scholar
52. M. E. Nuttall and J. M. Gimble, “Controlling the balance between osteoblastogenesis and adipogenesis and the consequent therapeutic implications,” Current Opinion in Pharmacology, vol. 4, no. 3, pp. 290–294, 2004. View at: Publisher Site | Google Scholar
53. R. Z. Birk, L. Abramovitch-Gottlib, and I. Margalit et al., “Conversion of adipogenic to osteogenic phenotype using crystalline porous biomatrices of marine origin,” Tissue Engineering, vol. 12, no. 1, pp. 21–31, 2006. View at: Publisher Site | Google Scholar
54. J. M. Gimble, S. Zvonic, Z. E. Floyd, M. Kassem, and M. E. Nuttall, “Playing with bone and fat,” Journal of Cellular Biochemistry, vol. 98, no. 2, pp. 251–266, 2006. View at: Publisher Site | Google Scholar
55. S. W. Kim, S. J. Her, S. Y. Kim, and C. S. Shin, “Ectopic overexpression of adipogenic transcription factors induces transdifferentiation of MC3T3-E1 osteoblasts,” Biochemical and Biophysical Research Communications, vol. 327, no. 3, pp. 811–819, 2005. View at: Publisher Site | Google Scholar
56. A. Yamashita, T. Takada, K. Nemoto, G. Yamamoto, and R. Torii, “Transient suppression of PPAR$\gamma$ directed ES cells into an osteoblastic lineage,” FEBS Letters, vol. 580, no. 17, pp. 4121–4125, 2006. View at: Publisher Site | Google Scholar
57. G. Sabatakos, N. A. Sims, and J. Chen et al., “Overexpression of $\Delta$FosB transcription factor(s) increases bone formation and inhibits adipogenesis,” Nature Medicine, vol. 6, no. 9, pp. 985–990, 2000. View at: Publisher Site | Google Scholar
58. M. Kveiborg, G. Sabatakos, and R. Chiusaroli et al., “$\Delta$FosB induces osteosclerosis and decreases adipogenesis by two independent cell-autonomous mechanisms,” Molecular and Cellular Biology, vol. 24, no. 7, pp. 2820–2830, 2004. View at: Publisher Site | Google Scholar
59. J.-H. Hong, E. S. Hwang, and M. T. McManus et al., “TAZ, a transcriptional modulator of mesenchymal stem cell differentiation,” Science, vol. 309, no. 5737, pp. 1074–1078, 2005. View at: Publisher Site | Google Scholar
60. E. Hu, P. Tontonoz, and B. M. Spiegelman, “Transdifferentiation of myoblasts by the adipogenic transcription factors PPAR$\gamma$ and C/EBP$\alpha$,” Proceedings of the National Academy of Sciences of the United States of America, vol. 92, no. 21, pp. 9856–9860, 1995. View at: Publisher Site | Google Scholar
61. D. Holst, S. Luquet, K. Kristiansen, and P. A. Grimaldi, “Roles of peroxisome proliferator-activated receptors delta and gamma in myoblast transdifferentiation,” Experimental Cell Research, vol. 288, no. 1, pp. 168–176, 2003. View at: Publisher Site | Google Scholar
62. S. E. Ross, N. Hemati, and K. A. Longo et al., “Inhibition of adipogenesis by Wnt signaling,” Science, vol. 289, no. 5481, pp. 950–953, 2000. View at: Publisher Site | Google Scholar
63. J. Liu and S. R. Farmer, “Regulating the balance between peroxisome proliferator-activated receptor $\gamma$ and $\beta$-catenin signaling during adipogenesis: a glycogen synthase kinase 3$\beta$ phosphorylation-defective mutant of $\beta$-catenin inhibits expression of a subset of adipogenic genes,” Journal of Biological Chemistry, vol. 279, no. 43, pp. 45020–45027, 2004. View at: Publisher Site | Google Scholar
64. H. S. Kim, L. Liang, R. G. Dean, D. B. Hausman, D. L. Hartzell, and C. A. Baile, “Inhibition of preadipocyte differentiation by myostatin treatment in 3T3-L1 cultures,” Biochemical and Biophysical Research Communications, vol. 281, no. 4, pp. 902–906, 2001. View at: Publisher Site | Google Scholar
65. J. N. Artaza, S. Bhasin, and T. R. Magee et al., “Myostatin inhibits myogenesis and promotes adipogenesis in C3H 10T(1/2) mesenchymal multipotent cells,” Endocrinology, vol. 146, no. 8, pp. 3547–3557, 2005. View at: Publisher Site | Google Scholar
66. B. J. Feldman, R. S. Streeper, R. V. Farese Jr., and K. R. Yamamoto, “Myostatin modulates adipogenesis to generate adipocytes with favorable metabolic effects,” Proceedings of the National Academy of Sciences of the United States of America, vol. 103, no. 42, pp. 15675–15680, 2006. View at: Publisher Site | Google Scholar
67. B. Cousin, O. Munoz, and M. Andre et al., “A role for preadipocytes as macrophage-like cells,” FASEB Journal, vol. 13, no. 2, pp. 305–312, 1999. View at: Google Scholar
68. C. Saillan-Barreau, B. Cousin, M. André, P. Villena, L. Casteilla, and L. Pénicaud, “Human adipose cells as candidates in defense and tissue remodeling phenomena,” Biochemical and Biophysical Research Communications, vol. 309, no. 3, pp. 502–505, 2003. View at: Publisher Site | Google Scholar
69. G. Charrière, B. Cousin, and E. Arnaud et al., “Preadipocyte conversion to macrophage: evidence of plasticity,” Journal of Biological Chemistry, vol. 278, no. 11, pp. 9850–9855, 2003. View at: Publisher Site | Google Scholar
70. H. Xu, G. T. Barnes, and Q. Yang et al., “Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance,” Journal of Clinical Investigation, vol. 112, no. 12, pp. 1821–1830, 2003. View at: Publisher Site | Google Scholar
71. R. Walczak and P. Tontonoz, “PPARadigms and PPARadoxes: expanding roles for PPAR$\gamma$ in the control of lipid metabolism,” Journal of Lipid Research, vol. 43, no. 2, pp. 177–186, 2002. View at: Google Scholar
72. K. J. Moore, E. D. Rosen, and M. L. Fitzgerald et al., “The role of PPAR-$\gamma$ in macrophage differentiation and cholesterol uptake,” Nature Medicine, vol. 7, no. 1, pp. 41–47, 2001. View at: Publisher Site | Google Scholar
73. M. Ricote, A. C. Li, T. M. Willson, C. J. Kelly, and C. K. Glass, “The peroxisome proliferator-activated receptor-$\gamma$ is a negative regulator of macrophage activation,” Nature, vol. 391, no. 6662, pp. 79–82, 1998. View at: Publisher Site | Google Scholar
74. A. C. Li, C. J. Binder, and A. Gutierrez et al., “Differential inhibition of macrophage foam-cell formation and atherosclerosis in mice by PPAR$\alpha$, $\beta /\delta$, and $\gamma$,” Journal of Clinical Investigation, vol. 114, no. 11, pp. 1564–1576, 2004. View at: Publisher Site | Google Scholar
75. H.-J. Lim, S. Lee, and K.-S. Lee et al., “PPAR$\gamma$ activation induces CD36 expression and stimulates foam cell like changes in rVSMCs,” Prostaglandins and Other Lipid Mediators, vol. 80, no. 3-4, pp. 165–174, 2006. View at: Publisher Site | Google Scholar

Copyright

Copyright © 2007 Louis Casteilla et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.