Abstract
A principal function of the PPARs is to act as regulators of lipid homeostasis by sensing changes in lipid metabolism through direct interactions with various fatty acids or their derivatives, and, thereby, to alter the expression of genes that control metabolic processes. PPARs have also been shown to participate in events that regulate the growth and differentiation of many cell types during the development of various tissues. This is particularly true of PPARγ, which has been shown to regulate preadipocyte differentiation during both white and brown adipose tissue development. The differentiation of preadipocytes into adipocytes is regulated by a network of transcription factors that interact to orchestrate the expression of many hundreds of proteins responsible for establishing the mature fat cell phenotype. At the center of this network is PPARγ, which is considered to function as a “master regulator” of adipogenesis. In this capacity, PPARγ directs the entire differentiation program by regulating the expression of many genes including those that code for transcription factors. Studies have also established an important role for PPARγ in regulating the switch between growth and differentiation during adipogenesis by actively suppressing cell cycle events.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Morrison RF, Farmer SR. Insights into the transcriptional control of adipocyte differentiation. J Cell Biochem 1999;Suppl 32–33:59–67.
Morrison RF, Farmer SR. Hormonal signaling and transcriptional control of adipocyte differentiation. J Nutr 2000; 130:3116–21.
Wu Z, Xie Y, Bucher NLR, Farmer SR. Conditional ectopic expression of C/EBPβ in NIH-3T3 cells induces PPARγ and stimulates adipogenesis. Genes Dev 1995;9:2350–63.
Wu Z, Bucher NLR, Farmer SR. Induction of peroxisome proliferator-activated receptor gamma during conversion of 3T3 fibroblasts into adipocytes is mediated by C/EBPβ, C/EBPδ and glucocorticoids. Mol Cell Biol 1996;16:4128–36.
Clarke SL, Robinson CE, Gimble JM. CAAT/enhancer binding proteins directly modulate transcription from the peroxisome proliferator-activated receptor g2 promoter. Biochem Biophys Res Commun 1997;240:99–103.
Hamm JK, Park BH, Farmer SR. A role for C/EBPβ in regulating peroxisome proliferators-activated receptor gamma activity during adipogenesis in 3T3-L1 preadipocytes. J Biol Chem 2001;276:18464–71.
Wu Z, Rosen ED, Brun R, et al. M. Cross-regulation of C/EBPβ and PPARγ controls the transcriptional pathway of adipogenesis and insulin sensitivity. Mol Cell 1999;3:151–58.
Fajas L, Schoonjans K, Gelman L, et al. 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;19:5495–503.
Tong Q, Dalgin G, Xu H, Ting CN, Leiden JM, Hotamisligil GS. Function of GATA transcription factors in preadipocyte-adipocyte transition. Science 2000;290:134–38.
Ross SE, Hemati N, Longo KA, et al. Inhibition of adipogenesis by Wnt signaling. Science 2000;289:950–53.
Moldes M, Lasnier F, Feve B, Pairault J, Djian P. Id3 prevents differentiation of preadipose cells. Mol Cell Biol 1997;17:1796–804.
Tontonoz P, Hu E, Graves RA, Budavari AI, Spiegelman BM. mPPARγ 2: Tissue-specific regulator of an adipocyte enhancer. Genes Dev 1994;8:1224–34.
Frohnert BI, Hui TY, Bernlohr DA. Identification of a functional peroxisome proliferators-responsive element in the murine fatty acid transport protein gene. J Biol Chem 1999;274:3970–77.
Tontonoz P, Hu E, Devine J, Beale EG, Spiegelman BM. PPAR gamma 2 regulates adipose expression of the phosphoenolpyruvate carboxykinase gene. Mol Cell Biol 1995;15:351–57.
Wu Z, Xie Y, Morrison RF, Bucher NLR, Farmer SR. PPARγ induces the insulin-dependent glucose transporter GLUT4 in the absence of C/EBPα during the conversion of 3T3 fibroblasts into adipocytes. J Clin Invest 1998;101:22–32.
Stephens JM, Morrison RF, Wu Z, Farmer SR. PPARgamma ligand-dependent induction of STAT1, STAT5A, and STAT5B during adipogenesis. Biochem Biophys Res Commun 1999;262:216–22.
Dixon TM, Daniel KW, Farmer SR, Collins S. CCAAT/enhancer-binding protein alpha is required for transcription of the beta 3-adrenergic receptor gene during adipogenesis. J Biol Chem 2001;276:722–28.
El-Jack AK, Hamm JK, Pilch PF, Farmer SR. Reconstitution of insulin-sensitive glucose transport in fibroblasts requires expression of both PPARγ and C/EBPα. J Biol Chem 1999;274:7946–51.
Kim JB, Wright HM, Wright M, Spiegelman BM. ADD1/SREBP1 activates PPAR gamma through the production of endogenous ligand. Proc Natl Acad Sci USA 1998;95:4333–37.
Morrison RF, Farmer SR. Role of PPARγ in regulating a cascade expression of cyclin-dependent kinase inhibitors, p18(INK4c) and p21 (Waf/Cip1), during adipogenesis. J Biol Chem 1999;274:17088–97.
Chen PL, Riley DJ, Chen Y, Lee WH. Retinoblastoma protein positively regulates terminal adipocyte differentiation through direct interaction with C/EBPs. Genes Dev 1996;10:2794–804.
Classon M, Kennedy BK, Mulloy R, Harlow E. Opposing roles of pRB and p107 in adipocyte differentiation. Proc Natl Acad Sci USA 2000;97:10826–31.
Altiok S, Xu M. Spiegelman BM. PPARgamma induces cell cycle withdrawal: Inhibition of E2F/DP DNA-binding activity via down-regulation of PP2A. Genes Dev 1997;11:1987–98.
Wang C, Fu M, D’Amico M, et al. Inhibition of cellular proliferation through IkappaB kinase-independent and peroxisome proliferator-activated receptor gamma-dependent repression of cyclin D1. Mol Cell Biol 2001;21:3057–70.
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2002 Springer Science+Business Media Dordrecht
About this chapter
Cite this chapter
Farmer, S.R., Prusty, D., Morrison, R.F., Moldes, M. (2002). PPARγ: A Regulator of Growth and Differentiation. In: Fruchart, JC., Gotto, A.M., Paoletti, R., Staels, B., Catapano, A.L. (eds) Peroxisome Proliferator Activated Receptors: From Basic Science to Clinical Applications. Medical Science Symposia Series, vol 18. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-1171-7_19
Download citation
DOI: https://doi.org/10.1007/978-1-4615-1171-7_19
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4613-5427-7
Online ISBN: 978-1-4615-1171-7
eBook Packages: Springer Book Archive