Nuclear Receptor Cofactors in PPARγ-Mediated Adipogenesis and Adipocyte Energy Metabolism

Transcriptional cofactors are integral to the proper function and regulation of nuclear receptors. Members of the peroxisome proliferator-activated receptor (PPAR) family of nuclear receptors are involved in the regulation of lipid and carbohydrate metabolism. They modulate gene transcription in response to a wide variety of ligands, a process that is mediated by transcriptional coactivators and corepressors. The mechanisms by which these cofactors mediate transcriptional regulation of nuclear receptor function are still being elucidated. The rapidly increasing array of cofactors has brought into focus the need for a clear understanding of how these cofactors interact in ligand- and cell-specific manners. This review highlights the differential effects of the assorted cofactors regulating the transcriptional action of PPARγ and summarizes the recent advances in understanding the physiological functions of corepressors and coactivators.

[1]  Jiandie D. Lin,et al.  Complementary action of the PGC-1 coactivators in mitochondrial biogenesis and brown fat differentiation. , 2006, Cell metabolism.

[2]  Béatrice Desvergne,et al.  From molecular action to physiological outputs: peroxisome proliferator-activated receptors are nuclear receptors at the crossroads of key cellular functions. , 2006, Progress in lipid research.

[3]  T. Hunter,et al.  Critical roles of the p160 transcriptional coactivators p/CIP and SRC-1 in energy balance. , 2006, Cell metabolism.

[4]  Michael Lehrke,et al.  The Many Faces of PPARγ , 2005, Cell.

[5]  Wei Xu.  Nuclear receptor coactivators: the key to unlock chromatin. , 2005, Biochemistry and cell biology = Biochimie et biologie cellulaire.

[6]  Michael G. Rosenfeld,et al.  Controlling nuclear receptors: the circular logic of cofactor cycles , 2005, Nature Reviews Molecular Cell Biology.

[7]  Christoph Handschin,et al.  Metabolic control through the PGC-1 family of transcription coactivators. , 2005, Cell metabolism.

[8]  M. Brady,et al.  The Nuclear Receptor Corepressors NCoR and SMRT Decrease Peroxisome Proliferator-activated Receptor γ Transcriptional Activity and Repress 3T3-L1 Adipogenesis* , 2005, Journal of Biological Chemistry.

[9]  M. Lazar,et al.  Corepressors selectively control the transcriptional activity of PPARgamma in adipocytes. , 2005, Genes & development.

[10]  S. Batra,et al.  Identification of promethin and PGLP as two novel up-regulated genes in PPARgamma1-induced adipogenic mouse liver. , 2004, Biochimie.

[11]  Jiandie D. Lin,et al.  Defects in Adaptive Energy Metabolism with CNS-Linked Hyperactivity in PGC-1α Null Mice , 2004, Cell.

[12]  Namjin Chung,et al.  Sirt1 promotes fat mobilization in white adipocytes by repressing PPAR-γ , 2004, Nature.

[13]  P. So,et al.  Nuclear receptor corepressor RIP140 regulates fat accumulation. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[14]  J. Auwerx,et al.  Transcription Factors and Nuclear Receptors Interact with the SWI/SNF Complex through the BAF60c Subunit* , 2004, Journal of Biological Chemistry.

[15]  G. Barish,et al.  PPARs and the complex journey to obesity , 2004, Nature Medicine.

[16]  C. Glass,et al.  A Corepressor/Coactivator Exchange Complex Required for Transcriptional Activation by Nuclear Receptors and Other Regulated Transcription Factors , 2004, Cell.

[17]  M. Privalsky,et al.  The role of corepressors in transcriptional regulation by nuclear hormone receptors. , 2004, Annual review of physiology.

[18]  D. Langin,et al.  Conversion from white to brown adipocytes: a strategy for the control of fat mass? , 2003, Trends in Endocrinology & Metabolism.

[19]  B. Spiegelman,et al.  Coordination of p300-mediated chromatin remodeling and TRAP/mediator function through coactivator PGC-1alpha. , 2003, Molecular cell.

[20]  Jiandie D. Lin,et al.  PGC-1β in the Regulation of Hepatic Glucose and Energy Metabolism* , 2003, Journal of Biological Chemistry.

[21]  L. Moore,et al.  Subtype specific effects of peroxisome proliferator-activated receptor ligands on corepressor affinity. , 2003, Biochemistry.

[22]  Jiandie D. Lin,et al.  Bioenergetic Analysis of Peroxisome Proliferator-activated Receptor γ Coactivators 1α and 1β (PGC-1α and PGC-1β) in Muscle Cells* , 2003, Journal of Biological Chemistry.

[23]  F. Winston,et al.  Recent advances in understanding chromatin remodeling by Swi/Snf complexes. , 2003, Current opinion in genetics & development.

[24]  Jun Qin,et al.  Purification and functional characterization of the human N‐CoR complex: the roles of HDAC3, TBL1 and TBLR1 , 2003, The EMBO journal.

[25]  W. Chin,et al.  Ligand and Coactivator Identity Determines the Requirement of the Charge Clamp for Coactivation of the Peroxisome Proliferator-activated Receptor γ* , 2003, The Journal of Biological Chemistry.

[26]  J. Gustafsson,et al.  Inactivation of the Nuclear Receptor Coactivator RAP250 in Mice Results in Placental Vascular Dysfunction , 2003, Molecular and Cellular Biology.

[27]  P. Puigserver,et al.  Peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1 alpha): transcriptional coactivator and metabolic regulator. , 2003, Endocrine reviews.

[28]  J. Reddy,et al.  Coactivator PRIP, the Peroxisome Proliferator-activated Receptor-interacting Protein, Is a Modulator of Placental, Cardiac, Hepatic, and Embryonic Development* , 2003, The Journal of Biological Chemistry.

[29]  J. Auwerx,et al.  SRC-1 and TIF2 Control Energy Balance between White and Brown Adipose Tissues , 2002, Cell.

[30]  B. O’Malley,et al.  Molecular Mechanisms and Cellular Biology of the Steroid Receptor Coactivator (SRC) Family in Steroid Receptor Function , 2002, Reviews in Endocrine and Metabolic Disorders.

[31]  S. Surapureddi,et al.  Identification of a transcriptionally active peroxisome proliferator-activated receptor α-interacting cofactor complex in rat liver and characterization of PRIC285 as a coactivator , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[32]  M. Rao,et al.  Interaction of PIMT with Transcriptional Coactivators CBP, p300, and PBP Differential Role in Transcriptional Regulation* , 2002, The Journal of Biological Chemistry.

[33]  B. Spiegelman,et al.  Transcription coactivator TRAP220 is required for PPARγ2-stimulated adipogenesis , 2002, Nature.

[34]  N. Aoki,et al.  Overexpression and Ribozyme-mediated Targeting of Transcriptional Coactivators CREB-binding Protein and p300 Revealed Their Indispensable Roles in Adipocyte Differentiation through the Regulation of Peroxisome Proliferator-activated Receptor γ* , 2002, The Journal of Biological Chemistry.

[35]  Karsten Kristiansen,et al.  Nuclear receptor corepressor-dependent repression of peroxisome-proliferator-activated receptor delta-mediated transactivation. , 2002, The Biochemical journal.

[36]  O. Hermanson,et al.  Nuclear receptor coregulators: multiple modes of modification , 2002, Trends in Endocrinology & Metabolism.

[37]  Jiandie D. Lin,et al.  Peroxisome Proliferator-activated Receptor γ Coactivator 1β (PGC-1β), A Novel PGC-1-related Transcription Coactivator Associated with Host Cell Factor* , 2002, The Journal of Biological Chemistry.

[38]  R. Tjian,et al.  Selectivity of chromatin-remodelling cofactors for ligand-activated transcription , 2001, Nature.

[39]  B. Spiegelman,et al.  Adipose tissue reduction in mice lacking the translational inhibitor 4E-BP1 , 2001, Nature Medicine.

[40]  P. Carlsson,et al.  FOXC2 Is a Winged Helix Gene that Counteracts Obesity, Hypertriglyceridemia, and Diet-Induced Insulin Resistance , 2001, Cell.

[41]  M. Rao,et al.  Cloning and characterization of PIMT, a protein with a methyltransferase domain, which interacts with and enhances nuclear receptor coactivator PRIP function , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[42]  M. Parker,et al.  Core LXXLL Motif Sequences in CREB-binding Protein, SRC1, and RIP140 Define Affinity and Selectivity for Steroid and Retinoid Receptors* , 2001, The Journal of Biological Chemistry.

[43]  R. Kingston,et al.  Purification and characterization of mSin3A-containing Brg1 and hBrm chromatin remodeling complexes. , 2001, Genes & development.

[44]  F Randazzo,et al.  A Brg1 null mutation in the mouse reveals functional differences among mammalian SWI/SNF complexes. , 2000, Molecular cell.

[45]  Neil J McKenna,et al.  From ligand to response: generating diversity in nuclear receptor coregulator function , 2000, The Journal of Steroid Biochemistry and Molecular Biology.

[46]  S. Kato,et al.  Ligand type-specific Interactions of Peroxisome Proliferator-activated Receptor γ with Transcriptional Coactivators* , 2000, The Journal of Biological Chemistry.

[47]  P. Puigserver,et al.  Direct coupling of transcription and mRNA processing through the thermogenic coactivator PGC-1. , 2000, Molecular cell.

[48]  R. Roeder,et al.  Transcriptional regulation through Mediator-like coactivators in yeast and metazoan cells. , 2000, Trends in biochemical sciences.

[49]  J. Reddy,et al.  Deletion of PBP/PPARBP, the Gene for Nuclear Receptor Coactivator Peroxisome Proliferator-activated Receptor-binding Protein, Results in Embryonic Lethality* , 2000, The Journal of Biological Chemistry.

[50]  M. Rao,et al.  Isolation and Characterization of Peroxisome Proliferator-activated Receptor (PPAR) Interacting Protein (PRIP) as a Coactivator for PPAR* , 2000, The Journal of Biological Chemistry.

[51]  J. Chen,et al.  The SRC family of nuclear receptor coactivators. , 2000, Gene.

[52]  E. Treuter,et al.  Cloning and Characterization of RAP250, a Novel Nuclear Receptor Coactivator* , 2000, The Journal of Biological Chemistry.

[53]  R. Evans,et al.  Mechanism of corepressor binding and release from nuclear hormone receptors. , 1999, Genes & development.

[54]  C. Glass,et al.  Molecular determinants of nuclear receptor-corepressor interaction. , 1999, Genes & development.

[55]  Guillaume Adelmant,et al.  Activation of PPARγ coactivator-1 through transcription factor docking , 1999 .

[56]  M. Lazar,et al.  The CoRNR motif controls the recruitment of corepressors by nuclear hormone receptors , 1999, Nature.

[57]  K. Chien,et al.  PPARγ Is Required for Placental, Cardiac, and Adipose Tissue Development , 1999 .

[58]  V. Mootha,et al.  Mechanisms Controlling Mitochondrial Biogenesis and Respiration through the Thermogenic Coactivator PGC-1 , 1999, Cell.

[59]  J. Auwerx,et al.  An update on the mechanisms of action of the peroxisome proliferator-activated receptors (PPARs) and their roles in inflammation and cancer , 1999, Cellular and Molecular Life Sciences CMLS.

[60]  M. Leid,et al.  Identification of Nuclear Receptor Corepressor as a Peroxisome Proliferator-activated Receptor α Interacting Protein* , 1999, The Journal of Biological Chemistry.

[61]  Paul Tempst,et al.  Ligand-dependent transcription activation by nuclear receptors requires the DRIP complex , 1999, Nature.

[62]  C. Glass,et al.  Coactivator and corepressor complexes in nuclear receptor function. , 1999, Current opinion in genetics & development.

[63]  J. Auwerx,et al.  p300 Interacts with the N- and C-terminal Part of PPARγ2 in a Ligand-independent and -dependent Manner, Respectively* , 1999, The Journal of Biological Chemistry.

[64]  M. Yaniv,et al.  Altered control of cellular proliferation in the absence of mammalian brahma (SNF2α) , 1998, The EMBO journal.

[65]  R. Roeder,et al.  The TRAP220 component of a thyroid hormone receptor- associated protein (TRAP) coactivator complex interacts directly with nuclear receptors in a ligand-dependent fashion. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[66]  C. Glass,et al.  Co-activators and co-repressors in the integration of transcriptional responses. , 1998, Current opinion in cell biology.

[67]  J. Gustafsson,et al.  A regulatory role for RIP140 in nuclear receptor activation. , 1998, Molecular endocrinology.

[68]  P. Puigserver,et al.  A Cold-Inducible Coactivator of Nuclear Receptors Linked to Adaptive Thermogenesis , 1998, Cell.

[69]  M. Rao,et al.  Isolation and Characterization of PBP, a Protein That Interacts with Peroxisome Proliferator-activated Receptor* , 1997, The Journal of Biological Chemistry.

[70]  J. Flier,et al.  Ligand-independent Activation Domain in the N Terminus of Peroxisome Proliferator-activated Receptor γ (PPARγ) , 1997, The Journal of Biological Chemistry.

[71]  J. Flier,et al.  Ligand-independent activation domain in the N terminus of peroxisome proliferator-activated receptor gamma (PPARgamma). Differential activity of PPARgamma1 and -2 isoforms and influence of insulin. , 1997, The Journal of biological chemistry.

[72]  David M. Heery,et al.  A signature motif in transcriptional co-activators mediates binding to nuclear receptors , 1997, Nature.

[73]  M. Jimenez-Linan,et al.  Peroxisome proliferator-activated receptor gene expression in human tissues. Effects of obesity, weight loss, and regulation by insulin and glucocorticoids. , 1997, The Journal of clinical investigation.

[74]  R. Roeder,et al.  Ligand induction of a transcriptionally active thyroid hormone receptor coactivator complex. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[75]  B. Spiegelman,et al.  Expression of the mitochondrial uncoupling protein gene from the aP2 gene promoter prevents genetic obesity. , 1995, The Journal of clinical investigation.

[76]  Thorsten Heinzel,et al.  Ligand-independent repression by the thyroid hormone receptor mediated by a nuclear receptor co-repressor , 1995, Nature.

[77]  R. Evans,et al.  A transcriptional co-repressor that interacts with nuclear hormone receptors , 1995, Nature.

[78]  P. Kushner,et al.  Nuclear factor RIP140 modulates transcriptional activation by the estrogen receptor. , 1995, The EMBO journal.

[79]  B. Spiegelman,et al.  Stimulation of adipogenesis in fibroblasts by PPARγ2, a lipid-activated transcription factor , 1994, Cell.

[80]  M. Lazar,et al.  Peroxisome proliferator-activated receptor (PPAR) gamma: adipose-predominant expression and induction early in adipocyte differentiation. , 1994, Endocrinology.

[81]  B. Spiegelman,et al.  mPPAR gamma 2: tissue-specific regulator of an adipocyte enhancer. , 1994, Genes & development.

[82]  K. Umesono,et al.  Convergence of 9-cis retinoic acid and peroxisome proliferator signalling pathways through heterodimer formation of their receptors , 1992, Nature.

[83]  I. Issemann,et al.  Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators , 1990, Nature.

[84]  C. Glass,et al.  Sensors and Signals: a Coactivator/ Corepressor/epigenetic Code for Integrating Signal-dependent Programs of Transcriptional Response , 2006 .

[85]  A. Imbalzano,et al.  of the Peroxisome Proliferator-Activated Receptor � Nuclear Hormone Receptor , 2003 .

[86]  B. Spiegelman.  Peroxisome Proliferator-Activated Receptor-Coactivator 1 ( PGC-1 ) : Transcriptional Coactivator and Metabolic Regulator , 2003 .

[87]  A. Wolffe,et al.  PPARγ knockdown by engineered transcription factors: exogenous PPARγ2 but not PPARγ1 reactivates adipogenesis , 2002 .

[88]  J. Berger,et al.  The mechanisms of action of PPARs. , 2002, Annual review of medicine.

[89]  C. Glass,et al.  Nuclear receptor coactivators. , 2000, Advances in pharmacology.

[90]  R. Roeder,et al.  Role of general and gene-specific cofactors in the regulation of eukaryotic transcription. , 1998, Cold Spring Harbor symposia on quantitative biology.