Adipocyte Precursors: Developmental Origins, Self-Renewal, and Plasticity

Chapter

Abstract

The current epidemic of obesity and overweight has caused a surge of interest in the study of adipose tissue formation. Much progress has been made in defining the transcriptional networks controlling the terminal differentiation of preadipocytes into mature adipocytes. However, the early steps that direct mesenchymal stem cells down the adipocyte lineage remain largely unknown. Similarly, the study of the developmental origin of adipocytes during embryogenesis has been largely disregarded until now. This review summarizes the surprising findings that have recently emerged from in vivo lineage tracing studies, unraveling unsuspected developmental origins for white adipocytes. We will propose that the differential origin of adipocytes could also reflect functional differences and site-specific regulations of adipose tissue. This chapter also reports recent work that has led to the identification of discrete immature cell populations from which white adipocytes are derived in mice.

A pool of adipocyte progenitors remains present in adipose tissue during adult life. This pool is responsible for the renewal of adipocytes and the potential of this tissue to expand in response to chronic energy overload. However, factors controlling proliferation and differentiation of human adipocyte progenitors are largely unknown. We will present stem cells derived from human adipose tissue (human Multipotent Adipose tissue Derived Stem (hMADS) cells) for studying proliferation and differentiation of adipocyte progenitors and will show that fibroblast growth factor 2 and activin A are key regulators of human adipocyte precursor self-renewal. Finally, we will discuss about the plasticity of hMADS cells.

Keywords

Adipocyte precursors Stem cells Adipose tissue Adipocyte development 

References

  1. Bezaire V, Mairal A, Ribet C, Lefort C, Girousse A, Jocken J, Laurencikiene J, Anesia R, Rodriguez A-M, Ryden M, Stenson BM, Dani C, Ailhaud G, Arner P, Langin D (2009) Contribution of adipose triglyceride lipase and hormone-sensitive lipase to lypolysis in human hMADS adipocytes. J Biol Chem 284(27):18282–18291PubMedCrossRefGoogle Scholar
  2. Billon N, Iannarelli P, Monteiro MC, Glavieux-Pardanaud C, Richardson WD, Kessaris N, Dani C, Dupin E (2007) The generation of adipocytes by the neural crest. Development 134:2283–2292PubMedCrossRefGoogle Scholar
  3. Billon N, Monteiro MC, Dani C (2008) Developmental origin of adipocytes: new insights into a pending question. Biol Cell 100:563–575PubMedCrossRefGoogle Scholar
  4. Billon N, Kolde R, Reimand J, Monteiro MC, Kull M, Peterson H, Tretyakov K, Adler P, Wdziekonski B, Vilo J, Dani C (2010) Comprehensive transcriptome analysis of mouse embryonic stem cell adipogenesis unravels new processes of adipocyte development. Genome Biol 11:R80PubMedCrossRefGoogle Scholar
  5. Bourlier V, Zakaroff-Girard A, Miranville A, De Barros S, Maumus M, Sengenes C, Galitzky J, Lafontan M, Karpe F, Frayn KN, Bouloumie A (2008) Remodeling phenotype of human subcutaneous adipose tissue macrophages. Circulation 117:806–815PubMedCrossRefGoogle Scholar
  6. Cancello R, Henegar C, Viguerie N, Taleb S, Poitou C, Rouault C, Coupaye M, Pelloux V, Hugol D, Bouillot JL, Bouloumie A, Barbatelli G, Cinti S, Svensson PA, Barsh GS, Zucker JD, Basdevant A, Langin D, Clement K (2005) Reduction of macrophage infiltration and chemoattractant gene expression changes in white adipose tissue of morbidly obese subjects after surgery-induced weight loss. Diabetes 54:2277–2286PubMedCrossRefGoogle Scholar
  7. Carnevalli LS, Masuda K, Frigerio F, Le Bacquer O, Um SH, Gandin V, Topisirovic I, Sonenberg N, Thomas G, Kozma SC (2010) S6K1 plays a critical role in early adipocyte differentiation. Dev Cell 18:763–774PubMedCrossRefGoogle Scholar
  8. Cousin B, Munoz O, Andre M, Fontanilles AM, Dani C, Cousin JL, Laharrague P, Casteilla L, Penicaud L (1999) A role for preadipocytes as macrophage-like cells. FASEB J 13:305–312PubMedGoogle Scholar
  9. Crossno JT Jr, Majka SM, Grazia T, Gill RG, Klemm DJ (2006) Rosiglitazone promotes development of a novel adipocyte population from bone marrow-derived circulating progenitor cells. J Clin Invest 116:3220–3228PubMedCrossRefGoogle Scholar
  10. Dani C, Smith A, Dessolin S, Leroy P, Staccini L, Villageois P, Darimont C, Ailhaud G (1997) Differentiation of embryonic stem cells into adipocytes in vitro. J Cell Sci 110:1279–1285PubMedGoogle Scholar
  11. Dupin E, Creuzet S, Le Douarin NM (2006) The contribution of the neural crest to the vertebrate body. Adv Exp Med Biol 589:96–119PubMedCrossRefGoogle Scholar
  12. Elabd C, Chiellini C, Massoudi A, Cochet O, Zaragosi LE, Trojani C, Michiels JF, Weiss P, Carle G, Rochet N, Dechesne CA, Ailhaud G, Dani C, Amri EZ (2007) Human adipose tissue-derived multipotent stem cells differentiate in vitro and in vivo into osteocyte-like cells. Biochem Biophys Res Commun 361:342–348PubMedCrossRefGoogle Scholar
  13. Elabd C, Chiellini C, Carmona M, Galitzky J, Cochet O, Petersen R, Penicaud L, Kristiansen K, Bouloumie A, Casteilla L, Dani C, Ailhaud G, Amri EZ (2009) Human multipotent adipose-derived stem cells differentiate into functional brown adipocytes. Stem Cells 27:2753–2760PubMedCrossRefGoogle Scholar
  14. Fontaine C, Cousin W, Plaisant M, Dani C, Peraldi P (2008) Hedgehog signaling alters adipocyte maturation of human mesenchymal stem cells. Stem Cells 26:1037–1046PubMedCrossRefGoogle Scholar
  15. Gesta S, Bluher M, Yamamoto Y, Norris AW, Berndt J, Kralisch S, Boucher J, Lewis C, Kahn CR (2006) Evidence for a role of developmental genes in the origin of obesity and body fat distribution. Proc Natl Acad Sci USA 103:6676–6681PubMedCrossRefGoogle Scholar
  16. Goodpaster BH, Wolf D (2004) Skeletal muscle lipid accumulation in obesity, insulin resistance, and type 2 diabetes. Pediatr Diabetes 5:219–226PubMedCrossRefGoogle Scholar
  17. Goudenege S, Pisani DF, Wdziekonski B, Di Santo JP, Bagnis C, Dani C, Dechesne CA (2009) Enhancement of myogenic and muscle repair capacities of human adipose-derived stem cells with forced expression of MyoD. Mol Ther 17:1064–1072PubMedCrossRefGoogle Scholar
  18. Hauner H, Entenmann G, Wabitsch M, Gaillard D, Ailhaud G, Negrel R, Pfeiffer EF (1989) Promoting effect of glucocorticoids on the differentiation of human adipocyte precursor cells cultured in a chemically defined medium. J Clin Invest 84:1663–1670PubMedCrossRefGoogle Scholar
  19. Isakson P, Hammarstedt A, Gustafson B, Smith U (2009) Impaired preadipocyte differentiation in human abdominal obesity: role of Wnt, tumor necrosis factor-alpha, and inflammation. Diabetes 58:1550–1557PubMedCrossRefGoogle Scholar
  20. Joe AW, Yi L, Natarajan A, Le Grand F, So L, Wang J, Rudnicki MA, Rossi FM (2010) Muscle injury activates resident fibro/adipogenic progenitors that facilitate myogenesis. Nat Cell Biol 12:153–163PubMedCrossRefGoogle Scholar
  21. Kawaguchi J, Mee PJ, Smith AG (2005) Osteogenic and chondrogenic differentiation of embryonic stem cells in response to specific growth factors. Bone 36:758–769PubMedCrossRefGoogle Scholar
  22. Keller GM (1995) In vitro differentiation of embryonic stem cells. Curr Opin Cell Biol 7:862–869PubMedCrossRefGoogle Scholar
  23. Keophiphath M, Achard V, Henegar C, Rouault C, Clement K, Lacasa D (2009) Macrophage-secreted factors promote a profibrotic phenotype in human preadipocytes. Mol Endocrinol 23:11–24PubMedCrossRefGoogle Scholar
  24. Lacasa D, Taleb S, Keophiphath M, Miranville A, Clement K (2007) Macrophage-secreted factors impair human adipogenesis: involvement of proinflammatory state in preadipocytes. Endocrinology 148:868–877PubMedCrossRefGoogle Scholar
  25. Lafontan M, Sengenes C, Galitzky J, Berlan M, De Glisezinski I, Crampes F, Stich V, Langin D, Barbe P, Riviere D (2000) Recent developments on lipolysis regulation in humans and discovery of a new lipolytic pathway. Int J Obes Relat Metab Disord 24(Suppl 4):S47–S52PubMedGoogle Scholar
  26. Li N, Kelsh RN, Croucher P, Roehl HH (2010) Regulation of neural crest cell fate by the retinoic acid and Pparg signalling pathways. Development 137:389–394PubMedCrossRefGoogle Scholar
  27. Longo KA, Wright WS, Kang S, Gerin I, Chiang SH, Lucas PC, Opp MR, MacDougald OA (2004) Wnt10b inhibits development of white and brown adipose tissues. J Biol Chem 279:35503–35509PubMedCrossRefGoogle Scholar
  28. Majka SM, Fox KE, Psilas JC, Helm KM, Childs CR, Acosta AS, Janssen RC, Friedman JE, Woessner BT, Shade TR, Varella-Garcia M, De KDJ (2010) novo generation of white adipocytes from the myeloid lineage via mesenchymal intermediates is age, adipose depot, and gender specific. Proc Natl Acad Sci USA 107:14781–14786PubMedCrossRefGoogle Scholar
  29. Maumus M, Sengenes C, Decaunes P, Zakaroff-Girard A, Bourlier V, Lafontan M, Galitzky J, Bouloumie A (2008) Evidence of in situ proliferation of adult adipose tissue-derived progenitor cells: influence of fat mass microenvironment and growth. J Clin Endocrinol Metab 93:4098–4106PubMedCrossRefGoogle Scholar
  30. Mohan A, Asselin J, Sargent IL, Groome NP, Muttukrishna S (2001) Effect of cytokines and growth factors on the secretion of inhibin A, activin A and follistatin by term placental villous trophoblasts in culture. Eur J Endocrinol 145:505–511PubMedCrossRefGoogle Scholar
  31. Montague CT, Prins JB, Sanders L, Zhang J, Sewter CP, Digby J, Byrne CD, O’Rahilly S (1998) Depot-related gene expression in human subcutaneous and omental adipocytes. Diabetes 47:1384–1391PubMedCrossRefGoogle Scholar
  32. Permana PA, Nair S, Lee YH, Luczy-Bachman G, Vozarova De Courten B, Tataranni PA (2004) Subcutaneous abdominal preadipocyte differentiation in vitro inversely correlates with central obesity. Am J Physiol Endocrinol Metab 286:E958–E962PubMedCrossRefGoogle Scholar
  33. Pisani DF, Dechesne CA, Sacconi S, Delplace S, Belmonte N, Cochet O, Clement N, Wdziekonski B, Villageois AP, Butori C, Bagnis C, Di Santo JP, Kurzenne JY, Desnuelle C, Dani C (2010) Isolation of a highly myogenic CD34-negative subset of human skeletal muscle cells free of adipogenic potential. Stem Cells 28:753–764PubMedCrossRefGoogle Scholar
  34. Poitou C, Divoux A, Faty A, Tordjman J, Hugol D, Aissat A, Keophiphath M, Henegar C, Commans S, Clement K (2009) Role of serum amyloid a in adipocyte-macrophage cross talk and adipocyte cholesterol efflux. J Clin Endocrinol Metab 94:1810–1817PubMedCrossRefGoogle Scholar
  35. Rodeheffer MS, Birsoy K, Friedman JM (2008) Identification of white adipocyte progenitor cells in vivo. Cell 135:240–249PubMedCrossRefGoogle Scholar
  36. Rodriguez A-M, Elabd C, Delteil F, Astier J, Vernochet C, Saint-Marc P, Guesnet J, Guezennec A, Amri E-Z, Dani C, Ailhaud G (2004) Adipocyte differentiation of multipotent cells established from human adipose tissue. Biochem Biophys Res Commun 315:255–263PubMedCrossRefGoogle Scholar
  37. Rodriguez A-M, Pisani D, Dechesne CA, Turc-Carel C, Kurzenne J-Y, Wdziekonski B, Villageois A, Bagnis C, Breittmayer J-P, Groux H, Ailhaud G, Dani C (2005a) Transplantation of a multipotent cell population from human adipose tissue induces dystrophin expression in the immunocompetent mdx mouse. J Exp Med 201:1397–1405PubMedCrossRefGoogle Scholar
  38. Rodriguez AM, Elabd C, Amri EZ, Ailhaud G, Dani C (2005b) The human adipose tissue is a source of multipotent stem cells. Biochimie 87:125–128PubMedCrossRefGoogle Scholar
  39. Rosen ED, MacDougald OA (2006) Adipocyte differentiation from the inside out. Nat Rev Mol Cell Biol 7:885–896PubMedCrossRefGoogle Scholar
  40. Rosen ED, Spiegelman BM (2000) Molecular regulation of adipogenesis. Annu Rev Cell Dev Biol 16:145–171PubMedCrossRefGoogle Scholar
  41. Schulz TJ, Tseng YH (2009) Emerging role of bone morphogenetic proteins in adipogenesis and energy metabolism. Cytokine Growth Factor Rev 20:523–531PubMedCrossRefGoogle Scholar
  42. Schulz H, Kolde R, Adler P, Aksoy I, Anastassiadis K, Bader M, Billon N, Boeuf H, Bourillot PY, Buchholz F, Dani C, Doss MX, Forrester L, Gitton M, Henrique D, Hescheler J, Himmelbauer H, Hubner N, Karantzali E, Kretsovali A, Lubitz S, Pradier L, Rai M, Reimand J, Rolletschek A, Sachinidis A, Savatier P, Stewart F, Storm MP, Trouillas M, Vilo J, Welham MJ, Winkler J, Wobus AM, Hatzopoulos AK (2009) The FunGenES database: a genomics resource for mouse embryonic stem cell differentiation. PLoS One 4:e6804PubMedCrossRefGoogle Scholar
  43. Seale P, Kajimura S, Spiegelman BM (2009) Transcriptional control of brown adipocyte development and physiological function – of mice and men. Genes Dev 23:788–797PubMedCrossRefGoogle Scholar
  44. Sengenes C, Lolmede K, Zakaroff-Girard A, Busse R, Bouloumie A (2005) Preadipocytes in the human subcutaneous adipose tissue display distinct features from the adult mesenchymal and hematopoietic stem cells. J Cell Physiol 205:114–122PubMedCrossRefGoogle Scholar
  45. Sera Y, LaRue AC, Moussa O, Mehrotra M, Duncan JD, Williams CR, Nishimoto E, Schulte BA, Watson PM, Watson DK, Ogawa M (2009) Hematopoietic stem cell origin of adipocytes. Exp Hematol 37:1108–1120, e1101–1104Google Scholar
  46. Sethi JK, Vidal-Puig AJ (2007) Thematic review series: adipocyte biology. Adipose tissue function and plasticity orchestrate nutritional adaptation. J Lipid Res 48:1253–1262PubMedCrossRefGoogle Scholar
  47. Smith AG (1992) Mouse embryo stem cells: their identification, propagation and manipulation. Semin Cell Biol 3:385–399PubMedCrossRefGoogle Scholar
  48. Spalding KL, Arner E, Westermark PO, Bernard S, Buchholz BA, Bergmann O, Blomqvist L, Hoffstedt J, Naslund E, Britton T, Concha H, Hassan M, Ryden M, Frisen J, Arner P (2008) Dynamics of fat cell turnover in humans. Nature 453:783–787PubMedCrossRefGoogle Scholar
  49. Takashima Y, Era T, Nakao K, Kondo S, Kasuga M, Smith AG, Nishikawa S (2007) Neuroepithelial cells supply an initial transient wave of MSC differentiation. Cell 129:1377–1388PubMedCrossRefGoogle Scholar
  50. Tang W, Zeve D, Suh JM, Bosnakovski D, Kyba M, Hammer RE, Tallquist MD, Graff JM (2008) White fat progenitor cells reside in the adipose vasculature. Science 322:583–586PubMedCrossRefGoogle Scholar
  51. Taura D, Noguchi M, Sone M, Hosoda K, Mori E, Okada Y, Takahashi K, Homma K, Oyamada N, Inuzuka M, Sonoyama T, Ebihara K, Tamura N, Itoh H, Suemori H, Nakatsuji N, Okano H, Yamanaka S, Nakao K (2009) Adipogenic differentiation of human induced pluripotent stem cells: comparison with that of human embryonic stem cells. FEBS Lett 583:1029–1033PubMedCrossRefGoogle Scholar
  52. Tchkonia T, Lenburg M, Thomou T, Giorgadze N, Frampton G, Pirtskhalava T, Cartwright A, Cartwright M, Flanagan J, Karagiannides I, Gerry N, Forse RA, Tchoukalova Y, Jensen MD, Pothoulakis C, Kirkland JL (2007) Identification of depot-specific human fat cell progenitors through distinct expression profiles and developmental gene patterns. Am J Physiol Endocrinol Metab 292:E298–E307PubMedCrossRefGoogle Scholar
  53. Timmons JA, Wennmalm K, Larsson O, Walden TB, Lassmann T, Petrovic N, Hamilton DL, Gimeno RE, Wahlestedt C, Baar K, Nedergaard J, Cannon B (2007) Myogenic gene expression signature establishes that brown and white adipocytes originate from distinct cell lineages. Proc Natl Acad Sci USA 104:4401–4406PubMedCrossRefGoogle Scholar
  54. Tong Q, Dalgin G, Xu H, Ting CN, Leiden JM, Hotamisligil GS (2000) Function of GATA transcription factors in preadipocyte-adipocyte transition. Science 290:134–138PubMedCrossRefGoogle Scholar
  55. Uezumi A, Fukada S, Yamamoto N, Takeda S, Tsuchida K (2010) Mesenchymal progenitors distinct from satellite cells contribute to ectopic fat cell formation in skeletal muscle. Nat Cell Biol 12:143–152PubMedCrossRefGoogle Scholar
  56. Wdziekonski B, Villageois P, Dani C (2003) Development of adipocytes from differentiated ES cells. Methods Enzymol 365:268–277PubMedCrossRefGoogle Scholar
  57. Wdziekonski B, Villageois P, Vernochet C, Phillips B, Dani C (2006) Use of differentiating embryonic stem cells in pharmacological studies. Methods Mol Biol 329:341–351PubMedGoogle Scholar
  58. Wdziekonski B, Villageois P, Dani C (2007) Differentiation of mouse embryonic stem cells and of human adult stem cells into adipocytes. Curr Protoc Cell Biol Chapter 23:Unit 23.4Google Scholar
  59. Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW Jr (2003) Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 112:1796–1808PubMedGoogle Scholar
  60. Widberg CH, Newell FS, Bachmann AW, Ramnoruth SN, Spelta MC, Whitehead JP, Hutley LJ, Prins JB (2009) Fibroblast growth factor receptor 1 is a key regulator of early adipogenic events in human preadipocytes. Am J Physiol Endocrinol Metab 296:E121–E131PubMedCrossRefGoogle Scholar
  61. Wren TA, Bluml S, Tseng-Ong L, Gilsanz V (2008) Three-point technique of fat quantification of muscle tissue as a marker of disease progression in Duchenne muscular dystrophy: preliminary study. AJR Am J Roentgenol 190:W8–W12PubMedCrossRefGoogle Scholar
  62. Xiong C, Xie CQ, Zhang L, Zhang J, Xu K, Fu M, Thompson WE, Yang LJ, Chen YE (2005) Derivation of adipocytes from human embryonic stem cells. Stem Cells Dev 14:671–675PubMedCrossRefGoogle Scholar
  63. Xu H, Barnes GT, Yang Q, Tan G, Yang D, Chou CJ, Sole J, Nichols A, Ross JS, Tartaglia LA, Chen H (2003) Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest 112:1821–1830PubMedGoogle Scholar
  64. Zaragosi LE, Ailhaud G, Dani C (2006) Autocrine fibroblast growth factor 2 signaling is critical for self-renewal of human multipotent adipose-derived stem cells. Stem Cells 24:2412–2419PubMedCrossRefGoogle Scholar
  65. Zaragosi LE, Wdziekonski B, Villageois P, Keophiphath M, Maumus M, Tchkonia T, Bourlier V, Mohsen-Kanson T, Ladoux A, Elabd C, Scheideler M, Trajanoski Z, Takashima Y, Amri EZ, Lacasa D, Sengenes C, Ailhaud G, Clement K, Bouloumie A, Kirkland JL, Dani C (2010) Activin A plays a critical role in proliferation and differentiation of human adipose progenitors. Diabetes 59(10):2513–2521PubMedCrossRefGoogle Scholar
  66. Zuk PA, Zhu M, Mizuno H, Huang J, Futrell JW, Katz AJ, Benhaim P, Lorenz HP, Hedrick MH (2001) Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng 7:211–228PubMedCrossRefGoogle Scholar
  67. Zuk PA, Zhu M, Ashjian P, De Ugarte DA, Huang JI, Mizuno H, Alfonso ZC, Fraser JK, Benhaim P, Hedrick MH (2002) Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell 13:4279–4295PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Institute of Developmental Biology and CancerUniversity of Nice Sophia-Antipolis, UMR6543 Centre National de la Recherche Scientifique (CNRS)Nice, Cedex 2France

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