Home LiteratureArticle Details
PMID: 17011499 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Review

Transcriptional control of adipocyte formation.

Cell metabolism ·Vol. 4 ·No. 4 ·2006-10-00 ·Pages 263-73

Farmer SR

Abstract

A detailed understanding of the processes governing adipose tissue formation will be instrumental in combating the obesity epidemic. Much progress has been made in the last two decades in defining transcriptional events controlling the differentiation of mesenchymal stem cells into adipocytes. A complex network of transcription factors and cell-cycle regulators, in concert with specific transcriptional coactivators and corepressors, respond to extracellular stimuli to activate or repress adipocyte differentiation. This review summarizes advances in this field, which constitute a framework for potential antiobesity strategies.

MeSH Terms
Adipocytes/cytology,metabolism Animals Cell Differentiation/genetics Gene Expression Regulation, Developmental Humans Models, Biological Transcription Factors/metabolism
Chemicals
Transcription Factors
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Farmer Stephen R
Department of Biochemistry, Boston University School of Medicine, Boston, Massachusetts 02118, USA. [email protected]
References (101)
101 references, click to expand
  1. Regulating the balance between peroxisome proliferator-activated receptor gamma and beta-catenin signaling during adipogenesis. A glycogen synthase kinase 3beta phosphorylation-defective mutant of beta-catenin inhibits expression of a subset of adipogenic genes.
    J Biol Chem. 2004 Oct 22;279(43):45020-7 PMID: 15308623
  2. ETO/MTG8 is an inhibitor of C/EBPbeta activity and a regulator of early adipogenesis.
    Mol Cell Biol. 2004 Nov;24(22):9863-72 PMID: 15509789
  3. Cyclin D1 inhibits peroxisome proliferator-activated receptor gamma-mediated adipogenesis through histone deacetylase recruitment.
    J Biol Chem. 2005 Apr 29;280(17):16934-41 PMID: 15713663
  4. Sequential phosphorylation of CCAAT enhancer-binding protein beta by MAPK and glycogen synthase kinase 3beta is required for adipogenesis.
    Proc Natl Acad Sci U S A. 2005 Jul 12;102(28):9766-71 PMID: 15985551
  5. A functional polymorphism in a STAT5B site of the human PPAR gamma 3 gene promoter affects height and lipid metabolism in a French population.
    Arterioscler Thromb Vasc Biol. 2003 Feb 1;23(2):289-94 PMID: 12588773
  6. A glucocorticoid-induced leucine-zipper protein, GILZ, inhibits adipogenesis of mesenchymal cells.
    EMBO Rep. 2003 Apr;4(4):374-80 PMID: 12671681
  7. Stimulation of preadipocyte differentiation by steroid through targeting of an HDAC1 complex.
    EMBO J. 2003 May 1;22(9):2135-45 PMID: 12727880
  8. Transcriptional coactivator PRIP, the peroxisome proliferator-activated receptor gamma (PPARgamma)-interacting protein, is required for PPARgamma-mediated adipogenesis.
    J Biol Chem. 2003 Jul 11;278(28):25281-4 PMID: 12754253
  9. Role of Foxa-2 in adipocyte metabolism and differentiation.
    J Clin Invest. 2003 Aug;112(3):345-56 PMID: 12865419
  10. Cyclin D1 repression of peroxisome proliferator-activated receptor gamma expression and transactivation.
    Mol Cell Biol. 2003 Sep;23(17):6159-73 PMID: 12917338
  11. Activation of CCAAT/enhancer-binding protein (C/EBP) alpha expression by C/EBP beta during adipogenesis requires a peroxisome proliferator-activated receptor-gamma-associated repression of HDAC1 at the C/ebp alpha gene promoter.
    J Biol Chem. 2006 Mar 24;281(12):7960-7 PMID: 16431920
  12. Complex role of the vitamin D receptor and its ligand in adipogenesis in 3T3-L1 cells.
    J Biol Chem. 2006 Apr 21;281(16):11205-13 PMID: 16467308
  13. Complementary action of the PGC-1 coactivators in mitochondrial biogenesis and brown fat differentiation.
    Cell Metab. 2006 May;3(5):333-41 PMID: 16679291
  14. Down-regulation of histone deacetylases stimulates adipocyte differentiation.
    J Biol Chem. 2006 Mar 10;281(10):6608-15 PMID: 16407282
  15. The orphan nuclear receptor Rev-Erbalpha is a peroxisome proliferator-activated receptor (PPAR) gamma target gene and promotes PPARgamma-induced adipocyte differentiation.
    J Biol Chem. 2003 Sep 26;278(39):37672-80 PMID: 12821652
  16. The TBN protein, which is essential for early embryonic mouse development, is an inducible TAFII implicated in adipogenesis.
    Mol Cell. 2003 Oct;12(4):991-1001 PMID: 14580349
  17. Compensation by the muscle limits the metabolic consequences of lipodystrophy in PPAR gamma hypomorphic mice.
    Proc Natl Acad Sci U S A. 2003 Nov 25;100(24):14457-62 PMID: 14603033
  18. Peroxisome-proliferator-activated receptor gamma suppresses Wnt/beta-catenin signalling during adipogenesis.
    Biochem J. 2003 Dec 15;376(Pt 3):607-13 PMID: 12954078
  19. Role of CREB in transcriptional regulation of CCAAT/enhancer-binding protein beta gene during adipogenesis.
    J Biol Chem. 2004 Feb 6;279(6):4471-8 PMID: 14593102
  20. Retinoblastoma protein functions as a molecular switch determining white versus brown adipocyte differentiation.
    Proc Natl Acad Sci U S A. 2004 Mar 23;101(12):4112-7 PMID: 15024128
  21. Dual roles for the Notch target gene Hes-1 in the differentiation of 3T3-L1 preadipocytes.
    Mol Cell Biol. 2004 Apr;24(8):3505-13 PMID: 15060169
  22. Oxygen-dependent regulation of adipogenesis.
    Methods Enzymol. 2004;381:387-95 PMID: 15063688
  23. Temporal recruitment of transcription factors and SWI/SNF chromatin-remodeling enzymes during adipogenic induction of the peroxisome proliferator-activated receptor gamma nuclear hormone receptor.
    Mol Cell Biol. 2004 Jun;24(11):4651-63 PMID: 15143161
  24. Nuclear receptor corepressor RIP140 regulates fat accumulation.
    Proc Natl Acad Sci U S A. 2004 Jun 1;101(22):8437-42 PMID: 15155905
  25. Sirt1 promotes fat mobilization in white adipocytes by repressing PPAR-gamma.
    Nature. 2004 Jun 17;429(6993):771-6 PMID: 15175761
  26. Selective disruption of PPARgamma 2 impairs the development of adipose tissue and insulin sensitivity.
    Proc Natl Acad Sci U S A. 2004 Jul 20;101(29):10703-8 PMID: 15249658
  27. Novel function of the retinoblastoma protein in fat: regulation of white versus brown adipocyte differentiation.
    Cell Cycle. 2004 Jun;3(6):774-8 PMID: 15197340
  28. Phosphorylation of C/EBPbeta at a consensus extracellular signal-regulated kinase/glycogen synthase kinase 3 site is required for the induction of adiponectin gene expression during the differentiation of mouse fibroblasts into adipocytes.
    Mol Cell Biol. 2004 Oct;24(19):8671-80 PMID: 15367685
  29. Krüppel-like factor-6 promotes preadipocyte differentiation through histone deacetylase 3-dependent repression of DLK1.
    J Biol Chem. 2005 Jul 22;280(29):26941-52 PMID: 15917248
  30. Krüppel-like transcription factor KLF5 is a key regulator of adipocyte differentiation.
    Cell Metab. 2005 Jan;1(1):27-39 PMID: 16054042
  31. Krox20 stimulates adipogenesis via C/EBPbeta-dependent and -independent mechanisms.
    Cell Metab. 2005 Feb;1(2):93-106 PMID: 16054051
  32. Metabolic control through the PGC-1 family of transcription coactivators.
    Cell Metab. 2005 Jun;1(6):361-70 PMID: 16054085
  33. The KLF2 transcription factor does not affect the formation of preadipocytes but inhibits their differentiation into adipocytes.
    Biochemistry. 2005 Aug 23;44(33):11098-105 PMID: 16101293
  34. Brain and muscle Arnt-like protein-1 (BMAL1), a component of the molecular clock, regulates adipogenesis.
    Proc Natl Acad Sci U S A. 2005 Aug 23;102(34):12071-6 PMID: 16093318
  35. A Nuclear Receptor Atlas: 3T3-L1 adipogenesis.
    Mol Endocrinol. 2005 Oct;19(10):2437-50 PMID: 16051663
  36. RIP140-targeted repression of gene expression in adipocytes.
    Mol Cell Biol. 2005 Nov;25(21):9383-91 PMID: 16227589
  37. Conditional deletion of beta-catenin in the mesenchyme of the developing mouse uterus results in a switch to adipogenesis in the myometrium.
    Dev Biol. 2005 Dec 1;288(1):276-83 PMID: 16256976
  38. Suppression of oxidative metabolism and mitochondrial biogenesis by the transcriptional corepressor RIP140 in mouse adipocytes.
    J Clin Invest. 2006 Jan;116(1):125-36 PMID: 16374519
  39. Hedgehog signaling plays a conserved role in inhibiting fat formation.
    Cell Metab. 2006 Jan;3(1):25-34 PMID: 16399502
  40. Temporal recruitment of CCAAT/enhancer-binding proteins to early and late adipogenic promoters in vivo.
    J Mol Endocrinol. 2006 Feb;36(1):139-51 PMID: 16461934
  41. Functional analysis of Hes-1 in preadipocytes.
    Mol Endocrinol. 2006 Mar;20(3):698-705 PMID: 16282371
  42. PPAR gamma is required for placental, cardiac, and adipose tissue development.
    Mol Cell. 1999 Oct;4(4):585-95 PMID: 10549290
  43. PPAR gamma is required for the differentiation of adipose tissue in vivo and in vitro.
    Mol Cell. 1999 Oct;4(4):611-7 PMID: 10549292
  44. Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase.
    Nature. 2000 Feb 17;403(6771):795-800 PMID: 10693811
  45. Mitotic clonal expansion during preadipocyte differentiation: calpain-mediated turnover of p27.
    J Biol Chem. 2000 Jun 9;275(23):17653-60 PMID: 10749891
  46. Inhibition of adipogenesis by Wnt signaling.
    Science. 2000 Aug 11;289(5481):950-3 PMID: 10937998
  47. Opposing roles of pRB and p107 in adipocyte differentiation.
    Proc Natl Acad Sci U S A. 2000 Sep 26;97(20):10826-31 PMID: 10995476
  48. Function of GATA transcription factors in preadipocyte-adipocyte transition.
    Science. 2000 Oct 6;290(5489):134-8 PMID: 11021798
  49. p300 coactivates the adipogenic transcription factor CCAAT/enhancer-binding protein alpha.
    J Biol Chem. 2001 May 11;276(19):16348-55 PMID: 11340085
  50. A role for C/EBPbeta in regulating peroxisome proliferator-activated receptor gamma activity during adipogenesis in 3T3-L1 preadipocytes.
    J Biol Chem. 2001 May 25;276(21):18464-71 PMID: 11279134
  51. Distinct transcriptional profiles of adipogenesis in vivo and in vitro.
    J Biol Chem. 2001 Sep 7;276(36):34167-74 PMID: 11445576
  52. C/EBPalpha is required for differentiation of white, but not brown, adipose tissue.
    Proc Natl Acad Sci U S A. 2001 Oct 23;98(22):12532-7 PMID: 11606718
  53. Cooperation between C/EBPalpha TBP/TFIIB and SWI/SNF recruiting domains is required for adipocyte differentiation.
    Genes Dev. 2001 Dec 1;15(23):3208-16 PMID: 11731483
  54. C/EBPalpha induces adipogenesis through PPARgamma: a unified pathway.
    Genes Dev. 2002 Jan 1;16(1):22-6 PMID: 11782441
  55. Increased insulin sensitivity despite lipodystrophy in Crebbp heterozygous mice.
    Nat Genet. 2002 Feb;30(2):221-6 PMID: 11818964
  56. Inhibition of PPAR gamma 2 gene expression by the HIF-1-regulated gene DEC1/Stra13: a mechanism for regulation of adipogenesis by hypoxia.
    Dev Cell. 2002 Mar;2(3):331-41 PMID: 11879638
  57. Transcription coactivator TRAP220 is required for PPAR gamma 2-stimulated adipogenesis.
    Nature. 2002 May 30;417(6888):563-7 PMID: 12037571
  58. E2Fs regulate adipocyte differentiation.
    Dev Cell. 2002 Jul;3(1):39-49 PMID: 12110166
  59. Genetic analysis of adipogenesis through peroxisome proliferator-activated receptor gamma isoforms.
    J Biol Chem. 2002 Nov 1;277(44):41925-30 PMID: 12200443
  60. The retinoblastoma-histone deacetylase 3 complex inhibits PPARgamma and adipocyte differentiation.
    Dev Cell. 2002 Dec;3(6):903-10 PMID: 12479814
  61. SRC-1 and TIF2 control energy balance between white and brown adipose tissues.
    Cell. 2002 Dec 27;111(7):931-41 PMID: 12507421
  62. Mitotic clonal expansion: a synchronous process required for adipogenesis.
    Proc Natl Acad Sci U S A. 2003 Jan 7;100(1):44-9 PMID: 12502791
  63. The forkhead transcription factor Foxo1 regulates adipocyte differentiation.
    Dev Cell. 2003 Jan;4(1):119-29 PMID: 12530968
  64. The Krüppel-like factor KLF2 inhibits peroxisome proliferator-activated receptor-gamma expression and adipogenesis.
    J Biol Chem. 2003 Jan 24;278(4):2581-4 PMID: 12426306
  65. STAT5A promotes adipogenesis in nonprecursor cells and associates with the glucocorticoid receptor during adipocyte differentiation.
    Diabetes. 2003 Feb;52(2):308-14 PMID: 12540601
  66. The forkhead transcription factor FoxC2 inhibits white adipocyte differentiation.
    J Biol Chem. 2004 Oct 8;279(41):42453-61 PMID: 15277530
  67. An established preadipose cell line and its differentiation in culture. II. Factors affecting the adipose conversion.
    Cell. 1975 May;5(1):19-27 PMID: 165899
  68. Spontaneous heritable changes leading to increased adipose conversion in 3T3 cells.
    Cell. 1976 Jan;7(1):105-13 PMID: 949738
  69. CCAAT/enhancer binding protein gene promoter: binding of nuclear factors during differentiation of 3T3-L1 preadipocytes.
    Proc Natl Acad Sci U S A. 1991 Mar 15;88(6):2593-7 PMID: 2006196
  70. Regulated expression of three C/EBP isoforms during adipose conversion of 3T3-L1 cells.
    Genes Dev. 1991 Sep;5(9):1538-52 PMID: 1840554
  71. mPPAR gamma 2: tissue-specific regulator of an adipocyte enhancer.
    Genes Dev. 1994 May 15;8(10):1224-34 PMID: 7926726
  72. Ectopic expression of the CCAAT/enhancer-binding protein alpha promotes the adipogenic program in a variety of mouse fibroblastic cells.
    Genes Dev. 1994 Jul 15;8(14):1654-63 PMID: 7958846
  73. Stimulation of adipogenesis in fibroblasts by PPAR gamma 2, a lipid-activated transcription factor.
    Cell. 1994 Dec 30;79(7):1147-56 PMID: 8001151
  74. Adipocyte-specific transcription factor ARF6 is a heterodimeric complex of two nuclear hormone receptors, PPAR gamma and RXR alpha.
    Nucleic Acids Res. 1994 Dec 25;22(25):5628-34 PMID: 7838715
  75. Cascade regulation of terminal adipocyte differentiation by three members of the C/EBP family of leucine zipper proteins.
    Genes Dev. 1995 Jan 15;9(2):168-81 PMID: 7531665
  76. Impaired energy homeostasis in C/EBP alpha knockout mice.
    Science. 1995 Aug 25;269(5227):1108-12 PMID: 7652557
  77. Conditional ectopic expression of C/EBP beta in NIH-3T3 cells induces PPAR gamma and stimulates adipogenesis.
    Genes Dev. 1995 Oct 1;9(19):2350-63 PMID: 7557387
  78. Inhibition of adipogenesis by the stress-induced protein CHOP (Gadd153).
    EMBO J. 1995 Oct 2;14(19):4654-61 PMID: 7588595
  79. ADD1/SREBP1 promotes adipocyte differentiation and gene expression linked to fatty acid metabolism.
    Genes Dev. 1996 May 1;10(9):1096-107 PMID: 8654925
  80. Induction of peroxisome proliferator-activated receptor gamma during the conversion of 3T3 fibroblasts into adipocytes is mediated by C/EBPbeta, C/EBPdelta, and glucocorticoids.
    Mol Cell Biol. 1996 Aug;16(8):4128-36 PMID: 8754811
  81. Retinoblastoma protein positively regulates terminal adipocyte differentiation through direct interaction with C/EBPs.
    Genes Dev. 1996 Nov 1;10(21):2794-804 PMID: 8946919
  82. Retinoic acid blocks adipogenesis by inhibiting C/EBPbeta-mediated transcription.
    Mol Cell Biol. 1997 Mar;17(3):1552-61 PMID: 9032283
  83. The organization, promoter analysis, and expression of the human PPARgamma gene.
    J Biol Chem. 1997 Jul 25;272(30):18779-89 PMID: 9228052
  84. Overexpression of Stra13, a novel retinoic acid-inducible gene of the basic helix-loop-helix family, inhibits mesodermal and promotes neuronal differentiation of P19 cells.
    Genes Dev. 1997 Aug 15;11(16):2052-65 PMID: 9284045
  85. CAAT/enhancer binding proteins directly modulate transcription from the peroxisome proliferator-activated receptor gamma 2 promoter.
    Biochem Biophys Res Commun. 1997 Nov 7;240(1):99-103 PMID: 9367890
  86. Defective adipocyte differentiation in mice lacking the C/EBPbeta and/or C/EBPdelta gene.
    EMBO J. 1997 Dec 15;16(24):7432-43 PMID: 9405372
  87. Nutritional and insulin regulation of fatty acid synthetase and leptin gene expression through ADD1/SREBP1.
    J Clin Invest. 1998 Jan 1;101(1):1-9 PMID: 9421459
  88. ADD1/SREBP1 activates PPARgamma through the production of endogenous ligand.
    Proc Natl Acad Sci U S A. 1998 Apr 14;95(8):4333-7 PMID: 9539737
  89. Stat5a and Stat5b proteins have essential and nonessential, or redundant, roles in cytokine responses.
    Cell. 1998 May 29;93(5):841-50 PMID: 9630227
  90. p300 interacts with the N- and C-terminal part of PPARgamma2 in a ligand-independent and -dependent manner, respectively.
    J Biol Chem. 1999 Mar 19;274(12):7681-8 PMID: 10075656
  91. Reconstitution of insulin-sensitive glucose transport in fibroblasts requires expression of both PPARgamma and C/EBPalpha.
    J Biol Chem. 1999 Mar 19;274(12):7946-51 PMID: 10075691
  92. Cross-regulation of C/EBP alpha and PPAR gamma controls the transcriptional pathway of adipogenesis and insulin sensitivity.
    Mol Cell. 1999 Feb;3(2):151-8 PMID: 10078198
  93. Role of PPARgamma in regulating a cascade expression of cyclin-dependent kinase inhibitors, p18(INK4c) and p21(Waf1/Cip1), during adipogenesis.
    J Biol Chem. 1999 Jun 11;274(24):17088-97 PMID: 10358062
  94. Regulation of peroxisome proliferator-activated receptor gamma expression by adipocyte differentiation and determination factor 1/sterol regulatory element binding protein 1: implications for adipocyte differentiation and metabolism.
    Mol Cell Biol. 1999 Aug;19(8):5495-503 PMID: 10409739
  95. Activation and centromeric localization of CCAAT/enhancer-binding proteins during the mitotic clonal expansion of adipocyte differentiation.
    Genes Dev. 1999 Sep 1;13(17):2231-41 PMID: 10485846
  96. Interaction between GATA and the C/EBP family of transcription factors is critical in GATA-mediated suppression of adipocyte differentiation.
    Mol Cell Biol. 2005 Jan;25(2):706-15 PMID: 15632071
  97. Regulation of osteoblastogenesis and bone mass by Wnt10b.
    Proc Natl Acad Sci U S A. 2005 Mar 1;102(9):3324-9 PMID: 15728361
  98. Nutrient control of glucose homeostasis through a complex of PGC-1alpha and SIRT1.
    Nature. 2005 Mar 3;434(7029):113-8 PMID: 15744310
  99. Delta-interacting protein A, a new inhibitory partner of CCAAT/enhancer-binding protein beta, implicated in adipocyte differentiation.
    J Biol Chem. 2005 Mar 25;280(12):11432-8 PMID: 15644333
  100. Role of Krüppel-like factor 15 (KLF15) in transcriptional regulation of adipogenesis.
    J Biol Chem. 2005 Apr 1;280(13):12867-75 PMID: 15664998
  101. The nuclear receptor corepressors NCoR and SMRT decrease peroxisome proliferator-activated receptor gamma transcriptional activity and repress 3T3-L1 adipogenesis.
    J Biol Chem. 2005 Apr 8;280(14):13600-5 PMID: 15691842
Article Info
Journal
Cell metabolism
Abbr.
Cell Metab
ISSN
1550-4131
DOI
10.1016/j.cmet.2006.07.001
Email
[email protected]
Published
2006-10-00
Pages
263-73
Language
English
Region
United States
NLM ID
101233170
PMCID
PMC1958996
Subset
IM
Grants
NIDDK NIH HHS · R56 DK051586 · United States
NIDDK NIH HHS · R01 DK051586 · United States
NIDDK NIH HHS · R01 DK058825 · United States
NIDDK NIH HHS · DK58825 · United States
NIDDK NIH HHS · R56 DK058825-06 · United States
NIDDK NIH HHS · R01 DK051586-10 · United States
NIDDK NIH HHS · DK51586 · United States
NIDDK NIH HHS · R56 DK058825 · United States
NIDDK NIH HHS · R01 DK058825-06A1 · United States
External Links
PubMed source DOI: 10.1016/j.cmet.2006.07.001 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2