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Physiol. Rev. 78: 783-809, 1998;
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PHYSIOLOGICAL REVIEWS   Vol. 78 No. 3 July 1998, pp. 783-809
Copyright ©1998 The American Physiological Society

Understanding Adipocyte Differentiation

FRANCINE M. GREGOIRE, CYNTHIA M. SMAS, AND HEI SOOK SUL

Department of Nutritional Sciences, University of California, Berkeley, California

Gregoire, Francine M., Cynthia M. Smas, and Hei Sook Sul. Understanding Adipocyte Differentiation. Physiol. Rev. 78: 783-809, 1998. --- The adipocyte plays a critical role in energy balance. Adipose tissue growth involves an increase in adipocyte size and the formation of new adipocytes from precursor cells. For the last 20 years, the cellular and molecular mechanisms of adipocyte differentiation have been extensively studied using preadipocyte culture systems. Committed preadipocytes undergo growth arrest and subsequent terminal differentiation into adipocytes. This is accompanied by a dramatic increase in expression of adipocyte genes including adipocyte fatty acid binding protein and lipid-metabolizing enzymes. Characterization of regulatory regions of adipose-specific genes has led to the identification of the transcription factors peroxisome proliferator-activated receptor-gamma (PPAR-gamma ) and CCAAT/enhancer binding protein (C/EBP), which play a key role in the complex transcriptional cascade during adipocyte differentiation. Growth and differentiation of preadipocytes is controlled by communication between individual cells or between cells and the extracellular environment. Various hormones and growth factors that affect adipocyte differentiation in a positive or negative manner have been identified. In addition, components involved in cell-cell or cell-matrix interactions such as preadipocyte factor-1 and extracellular matrix proteins are also pivotal in regulating the differentiation process. Identification of these molecules has yielded clues to the biochemical pathways that ultimately result in transcriptional activation via PPAR-gamma and C/EBP. Studies on the regulation of the these transcription factors and the mode of action of various agents that influence adipocyte differentiation will reveal the physiological and pathophysiological mechanisms underlying adipose tissue development.




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Testosterone Inhibits Adipogenic Differentiation in 3T3-L1 Cells: Nuclear Translocation of Androgen Receptor Complex with {beta}-Catenin and T-Cell Factor 4 May Bypass Canonical Wnt Signaling to Down-Regulate Adipogenic Transcription Factors
Endocrinology, January 1, 2006; 147(1): 141 - 154.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
M. Fu, M. Rao, T. Bouras, C. Wang, K. Wu, X. Zhang, Z. Li, T.-P. Yao, and R. G. Pestell
Cyclin D1 Inhibits Peroxisome Proliferator-activated Receptor {gamma}-mediated Adipogenesis through Histone Deacetylase Recruitment
J. Biol. Chem., April 29, 2005; 280(17): 16934 - 16941.
[Abstract] [Full Text] [PDF]

Home page
 CirculationHome page
R. Menghini, V. Marchetti, M. Cardellini, M. L. Hribal, A. Mauriello, D. Lauro, P. Sbraccia, R. Lauro, and M. Federici
Phosphorylation of GATA2 by Akt Increases Adipose Tissue Differentiation and Reduces Adipose Tissue-Related Inflammation: A Novel Pathway Linking Obesity to Atherosclerosis
Circulation, April 19, 2005; 111(15): 1946 - 1953.
[Abstract] [Full Text] [PDF]

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 Toxicol SciHome page
H. Masuno, J. Iwanami, T. Kidani, K. Sakayama, and K. Honda
Bisphenol A Accelerates Terminal Differentiation of 3T3-L1 Cells into Adipocytes through the Phosphatidylinositol 3-Kinase Pathway
Toxicol. Sci., April 1, 2005; 84(2): 319 - 327.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Endocrinol. Metab.Home page
H. Guan, E. Arany, J. P. van Beek, A. Chamson-Reig, S. Thyssen, D. J. Hill, and K. Yang
Adipose tissue gene expression profiling reveals distinct molecular pathways that define visceral adiposity in offspring of maternal protein-restricted rats
Am J Physiol Endocrinol Metab, April 1, 2005; 288(4): E663 - E673.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
O. Bezy, C. Elabd, O. Cochet, R. K. Petersen, K. Kristiansen, C. Dani, G. Ailhaud, and E.-Z. Amri
Delta-interacting Protein A, a New Inhibitory Partner of CCAAT/Enhancer-binding Protein {beta}, Implicated in Adipocyte Differentiation
J. Biol. Chem., March 25, 2005; 280(12): 11432 - 11438.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
J. D. Davies, K. L. H. Carpenter, I. R. Challis, N. L. Figg, R. McNair, D. Proudfoot, P. L. Weissberg, and C. M. Shanahan
Adipocytic Differentiation and Liver X Receptor Pathways Regulate the Accumulation of Triacylglycerols in Human Vascular Smooth Muscle Cells
J. Biol. Chem., February 4, 2005; 280(5): 3911 - 3919.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Endocrinol. Metab.Home page
T. Tchkonia, Y. D. Tchoukalova, N. Giorgadze, T. Pirtskhalava, I. Karagiannides, R. A. Forse, A. Koo, M. Stevenson, D. Chinnappan, A. Cartwright, et al.
Abundance of two human preadipocyte subtypes with distinct capacities for replication, adipogenesis, and apoptosis varies among fat depots
Am J Physiol Endocrinol Metab, January 1, 2005; 288(1): E267 - E277.
[Abstract] [Full Text] [PDF]

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 DiabetesHome page
L. Hutley, W. Shurety, F. Newell, R. McGeary, N. Pelton, J. Grant, A. Herington, D. Cameron, J. Whitehead, and J. Prins
Fibroblast Growth Factor 1: A Key Regulator of Human Adipogenesis
Diabetes, December 1, 2004; 53(12): 3097 - 3106.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
D. C. Lagace, R. S. McLeod, and M. W. Nachtigal
Valproic Acid Inhibits Leptin Secretion and Reduces Leptin Messenger Ribonucleic Acid Levels in Adipocytes
Endocrinology, December 1, 2004; 145(12): 5493 - 5503.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
L. Yue, N. Rasouli, G. Ranganathan, P. A. Kern, and T. Mazzone
Divergent Effects of Peroxisome Proliferator-activated Receptor {gamma} Agonists and Tumor Necrosis Factor {alpha} on Adipocyte ApoE Expression
J. Biol. Chem., November 12, 2004; 279(46): 47626 - 47632.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
J. A. Villena, S. Roy, E. Sarkadi-Nagy, K.-H. Kim, and H. S. Sul
Desnutrin, an Adipocyte Gene Encoding a Novel Patatin Domain-containing Protein, Is Induced by Fasting and Glucocorticoids: ECTOPIC EXPRESSION OF DESNUTRIN INCREASES TRIGLYCERIDE HYDROLYSIS
J. Biol. Chem., November 5, 2004; 279(45): 47066 - 47075.
[Abstract] [Full Text] [PDF]

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 J Mol EndocrinolHome page
C Bolduc, M Larose, M Yoshioka, P Ye, P Belleau, C Labrie, J Morissette, V Raymond, F Labrie, and J St-Amand
Effects of dihydrotestosterone on adipose tissue measured by serial analysis of gene expression
J. Mol. Endocrinol., October 1, 2004; 33(2): 429 - 444.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
J. Xu and K. Liao
Protein Kinase B/AKT 1 Plays a Pivotal Role in Insulin-like Growth Factor-1 Receptor Signaling Induced 3T3-L1 Adipocyte Differentiation
J. Biol. Chem., August 20, 2004; 279(34): 35914 - 35922.
[Abstract] [Full Text] [PDF]

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 J. Cell Sci.Home page
Y. Tanabe, M. Koga, M. Saito, Y. Matsunaga, and K. Nakayama
Inhibition of adipocyte differentiation by mechanical stretching through ERK-mediated downregulation of PPAR{gamma}2
J. Cell Sci., July 15, 2004; 117(16): 3605 - 3614.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
R.-Y. Yang, D. K. Hsu, L. Yu, H.-Y. Chen, and F.-T. Liu
Galectin-12 Is Required for Adipogenic Signaling and Adipocyte Differentiation
J. Biol. Chem., July 9, 2004; 279(28): 29761 - 29766.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
L. M. Scavo, M. Karas, M. Murray, and D. Leroith
Insulin-Like Growth Factor-I Stimulates Both Cell Growth and Lipogenesis during Differentiation of Human Mesenchymal Stem Cells into Adipocytes
J. Clin. Endocrinol. Metab., July 1, 2004; 89(7): 3543 - 3553.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
X. Su, D. J. Mancuso, P. E. Bickel, C. M. Jenkins, and R. W. Gross
Small Interfering RNA Knockdown of Calcium-independent Phospholipases A2 {beta} or {gamma} Inhibits the Hormone-induced Differentiation of 3T3-L1 Preadipocytes
J. Biol. Chem., May 21, 2004; 279(21): 21740 - 21748.
[Abstract] [Full Text] [PDF]

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 Mol. Biol. CellHome page
W. Zhang, L. Zhao, T. R. Lin, B. Chai, Y. Fan, I. Gantz, and M. W. Mulholland
Inhibition of Adipogenesis by Ghrelin
Mol. Biol. Cell, May 1, 2004; 15(5): 2484 - 2491.
[Abstract] [Full Text] [PDF]

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 Proc. Natl. Acad. Sci. USAHome page
K. Saeki, K. Matsumoto, M. Kinoshita, I. Suzuki, Y. Tasaka, K. Kano, Y. Taguchi, K. Mikami, M. Hirabayashi, N. Kashiwazaki, et al.
From The Cover: Functional expression of a {Delta}12 fatty acid desaturase gene from spinach in transgenic pigs
PNAS, April 27, 2004; 101(17): 6361 - 6366.
[Abstract] [Full Text] [PDF]

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 Proc. Natl. Acad. Sci. USAHome page
K.-H. Kim, L. Zhao, Y. Moon, C. Kang, and H. S. Sul
Dominant inhibitory adipocyte-specific secretory factor (ADSF)/resistin enhances adipogenesis and improves insulin sensitivity
PNAS, April 27, 2004; 101(17): 6780 - 6785.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
K. E. Hadri, M. Glorian, C. Monsempes, M.-N. Dieudonne, R. Pecquery, Y. Giudicelli, M. Andreani, I. Dugail, and B. Feve
In Vitro Suppression of the Lipogenic Pathway by the Nonnucleoside Reverse Transcriptase Inhibitor Efavirenz in 3T3 and Human Preadipocytes or Adipocytes
J. Biol. Chem., April 9, 2004; 279(15): 15130 - 15141.
[Abstract] [Full Text] [PDF]

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 J. Nutr.Home page
S. Urs, C. Smith, B. Campbell, A. M. Saxton, J. Taylor, B. Zhang, J. Snoddy, B. Jones Voy, and N. Moustaid-Moussa
Gene Expression Profiling in Human Preadipocytes and Adipocytes by Microarray Analysis
J. Nutr., April 1, 2004; 134(4): 762 - 770.
[Abstract] [Full Text] [PDF]

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 Proc. Natl. Acad. Sci. USAHome page
T. Imai, R. Takakuwa, S. Marchand, E. Dentz, J.-M. Bornert, N. Messaddeq, O. Wendling, M. Mark, B. Desvergne, W. Wahli, et al.
Peroxisome proliferator-activated receptor {gamma} is required in mature white and brown adipocytes for their survival in the mouse
PNAS, March 30, 2004; 101(13): 4543 - 4547.
[Abstract] [Full Text] [PDF]

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 Mol. Cell. Biol.Home page
Y.-H. Tseng, K. M. Kriauciunas, E. Kokkotou, and C. R. Kahn
Differential Roles of Insulin Receptor Substrates in Brown Adipocyte Differentiation
Mol. Cell. Biol., March 1, 2004; 24(5): 1918 - 1929.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Endocrinol. Metab.Home page
V. Serazin, M.-N. Dieudonne, M. Morot, P. de Mazancourt, and Y. Giudicelli
cAMP-positive regulation of angiotensinogen gene expression and protein secretion in rat adipose tissue
Am J Physiol Endocrinol Metab, March 1, 2004; 286(3): E434 - E438.
[Abstract] [Full Text] [PDF]

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 J ANIM SCIHome page
E. E. D. Felton and M. S. Kerley
Performance and carcass quality of steers fed whole raw soybeans at increasing inclusion levels
J Anim Sci, March 1, 2004; 82(3): 725 - 732.
[Abstract] [Full Text] [PDF]

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 J ANIM SCIHome page
J. Novakofski
Adipogenesis: Usefulness of in vitro and in vivo experimental models
J Anim Sci, March 1, 2004; 82(3): 905 - 915.
[Abstract] [Full Text] [PDF]

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 J ANIM SCIHome page
M. J. Azain
Role of fatty acids in adipocyte growth and development
J Anim Sci, March 1, 2004; 82(3): 916 - 924.
[Abstract] [Full Text] [PDF]

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 BloodHome page
Y. Tabe, M. Konopleva, M. F. Munsell, F. C. Marini, C. Zompetta, T. McQueen, T. Tsao, S. Zhao, S. Pierce, J. Igari, et al.
PML-RAR{alpha} is associated with leptin-receptor induction: the role of mesenchymal stem cell-derived adipocytes in APL cell survival
Blood, March 1, 2004; 103(5): 1815 - 1822.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Cell Mol. Bio.Home page
F. Zhang, T. Pan, L. D. Nielsen, and R. J. Mason
Lipogenesis in Fetal Rat Lung: Importance of C/EBP{alpha}, SREBP-1c, and Stearoyl-CoA Desaturase
Am. J. Respir. Cell Mol. Biol., February 1, 2004; 30(2): 174 - 183.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
N. M. Thompson, D. A. S. Gill, R. Davies, N. Loveridge, P. A. Houston, I. C. A. F. Robinson, and T. Wells
Ghrelin and Des-Octanoyl Ghrelin Promote Adipogenesis Directly in Vivo by a Mechanism Independent of the Type 1a Growth Hormone Secretagogue Receptor
Endocrinology, January 1, 2004; 145(1): 234 - 242.
[Abstract] [Full Text] [PDF]

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 J. Lipid Res.Home page
X. Nan, J.-X. Cheng, and X. S. Xie
Vibrational imaging of lipid droplets in live fibroblast cells with coherent anti-Stokes Raman scattering microscopy
J. Lipid Res., November 1, 2003; 44(11): 2202 - 2208.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
R. Singh, J. N. Artaza, W. E. Taylor, N. F. Gonzalez-Cadavid, and S. Bhasin
Androgens Stimulate Myogenic Differentiation and Inhibit Adipogenesis in C3H 10T1/2 Pluripotent Cells through an Androgen Receptor-Mediated Pathway
Endocrinology, November 1, 2003; 144(11): 5081 - 5088.
[Abstract] [Full Text] [PDF]


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