The elusive endogenous adipogenic PPARγ agonists: Lining up the suspects

Progress in Lipid Research

Volumn 61, Issue , 2016, Pages 149-162

  Hallenborg, Philip ^a,b   Petersen, Rasmus K ^a   Kouskoumvekaki, Irene ^c   Newman, John W ^d,e   Madsen, Lise ^a,f   Kristiansen, Karsten ^a  

^a UNIVERSITY OF COPENHAGEN   (Denmark)

^b UNIVERSITY OF SOUTHERN DENMARK   (Denmark)

^c TECHNICAL UNIVERSITY OF DENMARK   (Denmark)

^d AGRICULTURAL RESEARCH SERVICE   (United States)

^e UNIVERSITY OF CALIFORNIA   (United States)

^f INSTITUTE OF MARINE RESEARCH   (Norway)

Author keywords

15 dPGJ2 15 deoxy 12,14 prostaglandin J2; AA arachidonic acid; Abbreviations NO nitric oxide; ADH alcohol dehydrogenase; AF 1 ligand independent activation function; AF 2 ligand dependent activation function; azPC azelayol phosphatidylcholine; BAT Brown adipose tissue; C EBP CCAAT enhancer binding protein; CBR carbonyl reductase; ChREBP carbohydrate element binding protein; COX cyclooxygenase; CPA cyclic phosphatidic acid; cPLA2 cytosolic PLA2; CYP cytochrome P450 monooxygenase; DHET dihydroxyeicosatrienoic acid; DPEP dipeptidase; EET epoxyeicosatrienoic; EH epoxide hydrolase; ELOVL3 elongation of very long chain fatty acids 3; eLOX3 epidermis lipoxygenase type 3; EPA eicosapentaenoic acid; Epac exchange protein directly activated by cAMP; FAD flavin adenine dinucleotide; FAS fatty acid synthase; FFA free fatty acid; GGT gamma glutamyltransferase; GPC glycerophosphocholine; GPx glutathione peroxidase; HETE hydroxyeicosatrienoic acid; HODE hydroxyoctdecenonic acid; HPETE hydroperoxyeicosatetraenoic acid; HPGD 15 hydroxyprostaglandin dehydrogenase; HPODE hydroperoxyoctadecadienoic acid; IBMX isobutyl methylxanthine; KETE ketoeicosatetraenoic acid; LA linoleic acid; LBD ligand binding domain; LNO2 nitrolinoleic acid; LOX lipoxygenase; LPA lysophosphatidic acid; LTC4S leukotriene C4 synthase; MAPK mitogen activated protein kinase; MEF mouse embryonic fibroblast; Mo Co molybdenum cofactor; MUFA monounsaturated fatty acid; NO2 dioxide radical; NOS nitric oxide synthase; NOX4 NADPH oxidase 4; NR nuclear receptor; O2 superoxide; ONO2 peroxynitrite; PG prostaglandin; PGDH 15 hydroxyprostaglandin dehydrogenase; PGFS prostaglandin F synthase; PL phospholipase; PPAR peroxisome proliferator activated receptor ; PPRE peroxisome proliferator response element; pRB retinoblastoma protein; PTGDS prostaglandin D2 synthase; PTGES prostaglandin E synthase; PTGIS prostacyclin synthase; PTGR prostaglandin reductase; PTM post translational modification; PUFA polyunsaturated fatty acid; RetSat retinol saturase; ROS reactive oxygen species; RXR retinoic X receptor; sEH soluble epoxide hydrolase; SREBP 1c sterol regulatory element binding protein 1c; TBXAS thromboxane A synthase; TX thromboxane; TZD thiazolidinedione; UCP1 uncoupling protein 1; WAT white adipose tissue; XOR xanthine oxidoreductase

Indexed keywords

ENDOCANNABINOID; FATTY ACID; FATTY ACID DERIVATIVE; ICOSANOID; LIGAND; LINOLEIC ACID; LIPOXYGENASE; OLEIC ACID; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; PHOSPHOLIPID; POLYUNSATURATED FATTY ACID; PROSTAGLANDIN; XANTHINE OXIDASE;

ADIPOCYTE; ADIPOGENESIS; CELL DIFFERENTIATION; CELL MATURATION; CELL TRANSFORMATION; HUMAN; NONHUMAN; PRIORITY JOURNAL; RECEPTOR BINDING; REVIEW; ANIMAL; LIPID METABOLISM; METABOLISM; OXIDATION REDUCTION REACTION; PHYSIOLOGY;

ADIPOCYTES; ADIPOGENESIS; ANIMALS; FATTY ACIDS; HUMANS; LIPID METABOLISM; OXIDATION-REDUCTION; PPAR GAMMA; PROSTAGLANDINS;

EID: 84954049276     PISSN: 01637827     EISSN: 18732194     Source Type: Journal    
DOI: 10.1016/j.plipres.2015.11.002     Document Type: Review

References (212)

1. E.D. Rosen, and B.M. Spiegelman What we talk about when we talk about fat Cell 156 2014 20 44
2. J.V. Neel Diabetes mellitus: a "thrifty" genotype rendered detrimental by "progress"? Am. J. Hum. Genet. 14 1962 353 362
3. B. Cousin, S. Cinti, M. Morroni, S. Raimbault, D. Ricquier, L. Penicaud, and et al. Occurrence of brown adipocytes in rat white adipose tissue: molecular and morphological characterization J. Cell Sci. 103 Pt 4 1992 931 942
4. P. Young, J.R. Arch, and M. Ashwell Brown adipose tissue in the parametrial fat pad of the mouse FEBS Lett. 167 1984 10 14
5. P. Seale, B. Bjork, W. Yang, S. Kajimura, S. Chin, S. Kuang, and et al. PRDM16 controls a brown fat/skeletal muscle switch Nature 454 2008 961 967
6. J.A. Timmons, K. Wennmalm, O. Larsson, T.B. Walden, T. Lassmann, N. Petrovic, and et al. Myogenic gene expression signature establishes that brown and white adipocytes originate from distinct cell lineages Proc. Natl. Acad. Sci. U. S. A. 104 2007 4401 4406
7. J. Ishibashi, and P. Seale Medicine. Beige can be slimming Science 328 2010 1113 1114
8. N. Petrovic, T.B. Walden, I.G. Shabalina, J.A. Timmons, B. Cannon, and J. Nedergaard Chronic peroxisome proliferator-activated receptor gamma (PPARgamma) activation of epididymally derived white adipocyte cultures reveals a population of thermogenically competent, UCP1-containing adipocytes molecularly distinct from classic brown adipocytes J. Biol. Chem. 285 2010 7153 7164
9. L.Z. Sharp, K. Shinoda, H. Ohno, D.W. Scheel, E. Tomoda, L. Ruiz, and et al. Human BAT possesses molecular signatures that resemble beige/brite cells PLoS One 7 2012 e49452
10. J. Wu, P. Bostrom, L.M. Sparks, L. Ye, J.H. Choi, A.H. Giang, and et al. Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human Cell 150 2012 366 376
11. M.I. Lefterova, A.K. Haakonsson, M.A. Lazar, and S. Mandrup PPARgamma and the global map of adipogenesis and beyond Trends Endocrinol. Metab. 25 2014 293 302
12. S.A. Kliewer, B.M. Forman, B. Blumberg, E.S. Ong, U. Borgmeyer, D.J. Mangelsdorf, and et al. Differential expression and activation of a family of murine peroxisome proliferator-activated receptors Proc. Natl. Acad. Sci. U. S. A. 91 1994 7355 7359
13. P. Tontonoz, E. Hu, R.A. Graves, A.I. Budavari, and B.M. Spiegelman mPPAR gamma 2: tissue-specific regulator of an adipocyte enhancer Genes Dev. 8 1994 1224 1234
14. G.D. Barish, V.A. Narkar, and R.M. Evans PPAR delta: a dagger in the heart of the metabolic syndrome J. Clin. Invest. 116 2006 590 597
15. P. Lefebvre, G. Chinetti, J.C. Fruchart, and B. Staels Sorting out the roles of PPAR alpha in energy metabolism and vascular homeostasis J. Clin. Invest. 116 2006 571 580
16. R.K. Semple, V.K. Chatterjee, and S. O'Rahilly PPAR gamma and human metabolic disease J. Clin. Invest. 116 2006 581 589
17. Y. Zhu, C. Qi, J.R. Korenberg, X.N. Chen, D. Noya, M.S. Rao, and et al. Structural organization of mouse peroxisome proliferator-activated receptor gamma (mPPAR gamma) gene: alternative promoter use and different splicing yield two mPPAR gamma isoforms Proc. Natl. Acad. Sci. U. S. A. 92 1995 7921 7925
18. P. Tontonoz, E. Hu, and B.M. Spiegelman Stimulation of adipogenesis in fibroblasts by PPAR gamma 2, a lipid-activated transcription factor Cell 79 1994 1147 1156
19. J.M. Lehmann, L.B. Moore, T.A. Smith-Oliver, W.O. Wilkison, T.M. Willson, and S.A. Kliewer An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-activated receptor gamma (PPAR gamma) J. Biol. Chem. 270 1995 12953 12956
20. R.F. Kletzien, S.D. Clarke, and R.G. Ulrich Enhancement of adipocyte differentiation by an insulin-sensitizing agent Mol. Pharmacol. 41 1992 393 398
21. T. Sandouk, D. Reda, and C. Hofmann Antidiabetic agent pioglitazone enhances adipocyte differentiation of 3T3-F442A cells Am. J. Phys. 264 1993 C1600 C1608
22. E. Hu, P. Tontonoz, and B.M. Spiegelman Transdifferentiation of myoblasts by the adipogenic transcription factors PPAR gamma and C/EBP alpha Proc. Natl. Acad. Sci. U. S. A. 92 1995 9856 9860
23. B. Lecka-Czernik, I. Gubrij, E.J. Moerman, O. Kajkenova, D.A. Lipschitz, S.C. Manolagas, and et al. Inhibition of Osf2/Cbfa1 expression and terminal osteoblast differentiation by PPARgamma2 J. Cell. Biochem. 74 1999 357 371
24. E.D. Rosen, P. Sarraf, A.E. Troy, G. Bradwin, K. Moore, D.S. Milstone, and et al. PPAR gamma is required for the differentiation of adipose tissue in vivo and in vitro Mol. Cell 4 1999 611 617
25. N. Kubota, Y. Terauchi, H. Miki, H. Tamemoto, T. Yamauchi, K. Komeda, and et al. PPAR gamma mediates high-fat diet-induced adipocyte hypertrophy and insulin resistance Mol. Cell 4 1999 597 609
26. Y. Barak, M.C. Nelson, E.S. Ong, Y.Z. Jones, P. Ruiz-Lozano, K.R. Chien, and et al. PPAR gamma is required for placental, cardiac, and adipose tissue development Mol. Cell 4 1999 585 595
27. S.Z. Duan, C.Y. Ivashchenko, S.E. Whitesall, L.G. D'Alecy, D.C. Duquaine, F.C. Brosius 3rd, and et al. Hypotension, lipodystrophy, and insulin resistance in generalized PPARgamma-deficient mice rescued from embryonic lethality J. Clin. Invest. 117 2007 812 822
28. T. Yamauchi, J. Kamon, H. Waki, K. Murakami, K. Motojima, K. Komeda, and et al. The mechanisms by which both heterozygous peroxisome proliferator-activated receptor gamma (PPARgamma) deficiency and PPARgamma agonist improve insulin resistance J. Biol. Chem. 276 2001 41245 41254
29. P.D. Miles, Y. Barak, W. He, R.M. Evans, and J.M. Olefsky Improved insulin-sensitivity in mice heterozygous for PPAR-gamma deficiency J. Clin. Invest. 105 2000 287 292
30. J. Masugi, Y. Tamori, and M. Kasuga Inhibition of adipogenesis by a COOH-terminally truncated mutant of PPARgamma2 in 3T3-L1 cells Biochem. Biophys. Res. Commun. 264 1999 93 99
31. M. Gurnell, J.M. Wentworth, M. Agostini, M. Adams, T.N. Collingwood, C. Provenzano, and et al. A dominant-negative peroxisome proliferator-activated receptor gamma (PPARgamma) mutant is a constitutive repressor and inhibits PPARgamma-mediated adipogenesis J. Biol. Chem. 275 2000 5754 5759
32. Y. Park, B.D. Freedman, E.J. Lee, S. Park, and J.L. Jameson A dominant negative PPARgamma mutant shows altered cofactor recruitment and inhibits adipogenesis in 3T3-L1 cells Diabetologia 46 2003 365 377
33. B.D. Freedman, E.J. Lee, Y. Park, and J.L. Jameson A dominant negative peroxisome proliferator-activated receptor-gamma knock-in mouse exhibits features of the metabolic syndrome J. Biol. Chem. 280 2005 17118 17125
34. W. He, Y. Barak, A. Hevener, P. Olson, D. Liao, J. Le, and et al. Adipose-specific peroxisome proliferator-activated receptor gamma knockout causes insulin resistance in fat and liver but not in muscle Proc. Natl. Acad. Sci. U. S. A. 100 2003 15712 15717
35. T. Imai, R. Takakuwa, S. Marchand, E. Dentz, J.M. Bornert, N. Messaddeq, and et al. Peroxisome proliferator-activated receptor gamma is required in mature white and brown adipocytes for their survival in the mouse Proc. Natl. Acad. Sci. U. S. A. 101 2004 4543 4547
36. H. Koutnikova, T.A. Cock, M. Watanabe, S.M. Houten, M.F. Champy, A. Dierich, and et al. Compensation by the muscle limits the metabolic consequences of lipodystrophy in PPAR gamma hypomorphic mice Proc. Natl. Acad. Sci. U. S. A. 100 2003 14457 14462
37. I. Barroso, M. Gurnell, V.E. Crowley, M. Agostini, J.W. Schwabe, M.A. Soos, and et al. Dominant negative mutations in human PPARgamma associated with severe insulin resistance, diabetes mellitus and hypertension Nature 402 1999 880 883
38. D.B. Savage, G.D. Tan, C.L. Acerini, S.A. Jebb, M. Agostini, M. Gurnell, and et al. Human metabolic syndrome resulting from dominant-negative mutations in the nuclear receptor peroxisome proliferator-activated receptor-gamma Diabetes 52 2003 910 917
39. S.L. Gray, E. Dalla Nora, E.C. Backlund, M. Manieri, S. Virtue, R.C. Noland, and et al. Decreased brown adipocyte recruitment and thermogenic capacity in mice with impaired peroxisome proliferator-activated receptor (P465L PPARgamma) function Endocrinology 147 2006 5708 5714
40. Y.S. Tsai, H.J. Kim, N. Takahashi, H.S. Kim, J.R. Hagaman, J.K. Kim, and et al. Hypertension and abnormal fat distribution but not insulin resistance in mice with P465L PPARgamma J. Clin. Invest. 114 2004 240 249
41. S.L. Gray, E.D. Nora, J. Grosse, M. Manieri, T. Stoeger, G. Medina-Gomez, and et al. Leptin deficiency unmasks the deleterious effects of impaired peroxisome proliferator-activated receptor gamma function (P465L PPARgamma) in mice Diabetes 55 2006 2669 2677
42. D. Ren, T.N. Collingwood, E.J. Rebar, A.P. Wolffe, and H.S. Camp PPARgamma knockdown by engineered transcription factors: exogenous PPARgamma2 but not PPARgamma1 reactivates adipogenesis Genes Dev. 16 2002 27 32
43. E. Mueller, S. Drori, A. Aiyer, J. Yie, P. Sarraf, H. Chen, and et al. Genetic analysis of adipogenesis through peroxisome proliferator-activated receptor gamma isoforms J. Biol. Chem. 277 2002 41925 41930
44. J. Zhang, M. Fu, T. Cui, C. Xiong, K. Xu, W. Zhong, and et al. Selective disruption of PPARgamma 2 impairs the development of adipose tissue and insulin sensitivity Proc. Natl. Acad. Sci. U. S. A. 101 2004 10703 10708
45. G. Medina-Gomez, S. Virtue, C. Lelliott, R. Boiani, M. Campbell, C. Christodoulides, and et al. The link between nutritional status and insulin sensitivity is dependent on the adipocyte-specific peroxisome proliferator-activated receptor-gamma2 isoform Diabetes 54 2005 1706 1716
46. E. Hu, J.B. Kim, P. Sarraf, and B.M. Spiegelman Inhibition of adipogenesis through MAP kinase-mediated phosphorylation of PPARgamma Science 274 1996 2100 2103
47. S.M. Rangwala, B. Rhoades, J.S. Shapiro, A.S. Rich, J.K. Kim, G.I. Shulman, and et al. Genetic modulation of PPARgamma phosphorylation regulates insulin sensitivity Dev. Cell 5 2003 657 663
48. C.A. Argmann, T.A. Cock, and J. Auwerx Peroxisome proliferator-activated receptor gamma: the more the merrier? Eur. J. Clin. Investig. 35 2005 82 92 (discussion 80)
49. T.A. Cock, S.M. Houten, and J. Auwerx Peroxisome proliferator-activated receptor-gamma: too much of a good thing causes harm EMBO Rep. 5 2004 142 147
50. P. Tontonoz, R.A. Graves, A.I. Budavari, H. Erdjument-Bromage, M. Lui, E. Hu, and et al. Adipocyte-specific transcription factor ARF6 is a heterodimeric complex of two nuclear hormone receptors, PPAR gamma and RXR alpha Nucleic Acids Res. 22 1994 5628 5634
51. R. Siersbaek, R. Nielsen, S. John, M.H. Sung, S. Baek, A. Loft, and et al. Extensive chromatin remodelling and establishment of transcription factor 'hotspots' during early adipogenesis EMBO J. 30 2011 1459 1472
52. M.I. Lefterova, Y. Zhang, D.J. Steger, M. Schupp, J. Schug, A. Cristancho, and et al. PPARgamma and C/EBP factors orchestrate adipocyte biology via adjacent binding on a genome-wide scale Genes Dev. 22 2008 2941 2952
53. M.S. Madsen, R. Siersbaek, M. Boergesen, R. Nielsen, and S. Mandrup Peroxisome proliferator-activated receptor gamma and C/EBPalpha synergistically activate key metabolic adipocyte genes by assisted loading Mol. Cell. Biol. 34 2014 939 954
54. R. Nielsen, T.A. Pedersen, D. Hagenbeek, P. Moulos, R. Siersbaek, E. Megens, and et al. Genome-wide profiling of PPARgamma:RXR and RNA polymerase II occupancy reveals temporal activation of distinct metabolic pathways and changes in RXR dimer composition during adipogenesis Genes Dev. 22 2008 2953 2967
55. R. Siersbaek, A. Rabiee, R. Nielsen, S. Sidoli, S. Traynor, A. Loft, and et al. Transcription factor cooperativity in early adipogenic hotspots and super-enhancers Cell Rep. 7 2014 1443 1455
56. P. Puigserver, Z. Wu, C.W. Park, R. Graves, M. Wright, and B.M. Spiegelman A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis Cell 92 1998 829 839
57. M. Uldry, W. Yang, J. St-Pierre, J. Lin, P. Seale, and B.M. Spiegelman Complementary action of the PGC-1 coactivators in mitochondrial biogenesis and brown fat differentiation Cell Metab. 3 2006 333 341
58. E. Powell, P. Kuhn, and W. Xu Nuclear receptor cofactors in PPARgamma-mediated adipogenesis and adipocyte energy metabolism PPAR Res. 2007 2007 53843
59. V. Perissi, and M.G. Rosenfeld Controlling nuclear receptors: the circular logic of cofactor cycles Nat. Rev. Mol. Cell Biol. 6 2005 542 554
60. H.P. Guan, T. Ishizuka, P.C. Chui, M. Lehrke, and M.A. Lazar Corepressors selectively control the transcriptional activity of PPARgamma in adipocytes Genes Dev. 19 2005 453 461
61. I. Szatmari, P. Gogolak, J.S. Im, B. Dezso, E. Rajnavolgyi, and L. Nagy Activation of PPARgamma specifies a dendritic cell subtype capable of enhanced induction of iNKT cell expansion Immunity 21 2004 95 106
62. A.K. Haakonsson, M. Stahl Madsen, R. Nielsen, A. Sandelin, and S. Mandrup Acute genome-wide effects of rosiglitazone on PPARgamma transcriptional networks in adipocytes Mol. Endocrinol. 27 2013 1536 1549
63. S.E. Step, H.W. Lim, J.M. Marinis, A. Prokesch, D.J. Steger, S.H. You, and et al. Anti-diabetic rosiglitazone remodels the adipocyte transcriptome by redistributing transcription to PPARgamma-driven enhancers Genes Dev. 28 2014 1018 1028
64. M. Adams, M.J. Reginato, D. Shao, M.A. Lazar, and V.K. Chatterjee Transcriptional activation by peroxisome proliferator-activated receptor gamma is inhibited by phosphorylation at a consensus mitogen-activated protein kinase site J. Biol. Chem. 272 1997 5128 5132
65. E. Compe, P. Drane, C. Laurent, K. Diderich, C. Braun, J.H. Hoeijmakers, and et al. Dysregulation of the peroxisome proliferator-activated receptor target genes by XPD mutations Mol. Cell. Biol. 25 2005 6065 6076
66. I. Iankova, R.K. Petersen, J.S. Annicotte, C. Chavey, J.B. Hansen, I. Kratchmarova, and et al. Peroxisome proliferator-activated receptor gamma recruits the positive transcription elongation factor b complex to activate transcription and promote adipogenesis Mol. Endocrinol. 20 2006 1494 1505
67. J.H. Choi, A.S. Banks, J.L. Estall, S. Kajimura, P. Bostrom, D. Laznik, and et al. Anti-diabetic drugs inhibit obesity-linked phosphorylation of PPARgamma by Cdk5 Nature 466 2010 451 456
68. L. Qiang, L. Wang, N. Kon, W. Zhao, S. Lee, Y. Zhang, and et al. Brown remodeling of white adipose tissue by SirT1-dependent deacetylation of Ppargamma Cell 150 2012 620 632
69. T. Ohshima, H. Koga, and K. Shimotohno Transcriptional activity of peroxisome proliferator-activated receptor gamma is modulated by SUMO-1 modification J. Biol. Chem. 279 2004 29551 29557
70. S. Ji, S.Y. Park, J. Roth, H.S. Kim, and J.W. Cho O-GlcNAc modification of PPARgamma reduces its transcriptional activity Biochem. Biophys. Res. Commun. 417 2012 1158 1163
71. D. Bishop-Bailey, and J. Wray Peroxisome proliferator-activated receptors: a critical review on endogenous pathways for ligand generation Prostaglandins Other Lipid Mediat. 71 2003 1 22
72. R.T. Nolte, G.B. Wisely, S. Westin, J.E. Cobb, M.H. Lambert, R. Kurokawa, and et al. Ligand binding and co-activator assembly of the peroxisome proliferator-activated receptor-gamma Nature 395 1998 137 143
73. J. Uppenberg, C. Svensson, M. Jaki, G. Bertilsson, L. Jendeberg, and A. Berkenstam Crystal structure of the ligand binding domain of the human nuclear receptor PPARgamma J. Biol. Chem. 273 1998 31108 31112
74. T. Itoh, L. Fairall, K. Amin, Y. Inaba, A. Szanto, B.L. Balint, and et al. Structural basis for the activation of PPARgamma by oxidized fatty acids Nat. Struct. Mol. Biol. 15 2008 924 931
75. T. Waku, T. Shiraki, T. Oyama, K. Maebara, R. Nakamori, and K. Morikawa The nuclear receptor PPARgamma individually responds to serotonin- and fatty acid-metabolites EMBO J. 29 2010 3395 3407
76. T. Waku, T. Shiraki, T. Oyama, Y. Fujimoto, K. Maebara, N. Kamiya, and et al. Structural insight into PPARgamma activation through covalent modification with endogenous fatty acids J. Mol. Biol. 385 2009 188 199
77. T.S. Hughes, P.K. Giri, I.M. de Vera, D.P. Marciano, D.S. Kuruvilla, Y. Shin, and et al. An alternate binding site for PPARgamma ligands Nat. Commun. 5 2014 3571
78. J.B. Bruning, M.J. Chalmers, S. Prasad, S.A. Busby, T.M. Kamenecka, Y. He, and et al. Partial agonists activate PPARgamma using a helix 12 independent mechanism Structure 15 2007 1258 1271
79. J.H. Choi, A.S. Banks, T.M. Kamenecka, S.A. Busby, M.J. Chalmers, N. Kumar, and et al. Antidiabetic actions of a non-agonist PPARgamma ligand blocking Cdk5-mediated phosphorylation Nature 477 2011 477 481
80. H.S. Camp, A. Chaudhry, and T. Leff A novel potent antagonist of peroxisome proliferator-activated receptor gamma blocks adipocyte differentiation but does not revert the phenotype of terminally differentiated adipocytes Endocrinology 142 2001 3207 3213
81. J.L. Oberfield, J.L. Collins, C.P. Holmes, D.M. Goreham, J.P. Cooper, J.E. Cobb, and et al. A peroxisome proliferator-activated receptor gamma ligand inhibits adipocyte differentiation Proc. Natl. Acad. Sci. U. S. A. 96 1999 6102 6106
82. I. Tzameli, H. Fang, M. Ollero, H. Shi, J.K. Hamm, P. Kievit, and et al. Regulated production of a peroxisome proliferator-activated receptor-gamma ligand during an early phase of adipocyte differentiation in 3T3-L1 adipocytes J. Biol. Chem. 279 2004 36093 36102
83. C. Elabd, C. Chiellini, M. Carmona, J. Galitzky, O. Cochet, R. Petersen, and et al. Human multipotent adipose-derived stem cells differentiate into functional brown adipocytes Stem Cells 27 2009 2753 2760
84. A. Loft, I. Forss, M.S. Siersbaek, S.F. Schmidt, A.S. Larsen, J.G. Madsen, and et al. Browning of human adipocytes requires KLF11 and reprogramming of PPARgamma superenhancers Genes Dev. 2014
85. C.J. Walkey, and B.M. Spiegelman A functional peroxisome proliferator-activated receptor-gamma ligand-binding domain is not required for adipogenesis J. Biol. Chem. 283 2008 24290 24294
86. L. Madsen, R.K. Petersen, M.B. Sorensen, C. Jorgensen, P. Hallenborg, L. Pridal, and et al. Adipocyte differentiation of 3T3-L1 preadipocytes is dependent on lipoxygenase activity during the initial stages of the differentiation process Biochem. J. 375 2003 539 549
87. L.S. Doshi, M.K. Brahma, U.A. Bahirat, A.V. Dixit, and K.V. Nemmani Discovery and development of selective PPAR gamma modulators as safe and effective antidiabetic agents Expert Opin. Investig. Drugs 19 2010 489 512
88. M. Penumetcha, and N. Santanam Nutraceuticals as ligands of PPARgamma PPAR Res. 2012 2012 858352
89. L. Wang, B. Waltenberger, E.M. Pferschy-Wenzig, M. Blunder, X. Liu, C. Malainer, and et al. Natural product agonists of peroxisome proliferator-activated receptor gamma (PPARgamma): a review Biochem. Pharmacol. 2014
90. T.E. Johnson, M.K. Holloway, R. Vogel, S.J. Rutledge, J.J. Perkins, G.A. Rodan, and et al. Structural requirements and cell-type specificity for ligand activation of peroxisome proliferator-activated receptors J. Steroid Biochem. Mol. Biol. 63 1997 1 8
91. S.A. Kliewer, S.S. Sundseth, S.A. Jones, P.J. Brown, G.B. Wisely, C.S. Koble, and et al. Fatty acids and eicosanoids regulate gene expression through direct interactions with peroxisome proliferator-activated receptors alpha and gamma Proc. Natl. Acad. Sci. U. S. A. 94 1997 4318 4323
92. K. Yu, W. Bayona, C.B. Kallen, H.P. Harding, C.P. Ravera, G. McMahon, and et al. Differential activation of peroxisome proliferator-activated receptors by eicosanoids J. Biol. Chem. 270 1995 23975 23983
93. H. Keller, C. Dreyer, J. Medin, A. Mahfoudi, K. Ozato, and W. Wahli Fatty acids and retinoids control lipid metabolism through activation of peroxisome proliferator-activated receptor-retinoid X receptor heterodimers Proc. Natl. Acad. Sci. U. S. A. 90 1993 2160 2164
94. L. Madsen, R.K. Petersen, and K. Kristiansen Regulation of adipocyte differentiation and function by polyunsaturated fatty acids Biochim. Biophys. Acta 2005 1740 266 286
95. T. Kobayashi, and K. Fujimori Very long-chain-fatty acids enhance adipogenesis through coregulation of Elovl3 and PPARgamma in 3T3-L1 cells Am. J. Physiol. Endocrinol. Metab. 302 2012 E1461 E1471
96. T. Shiraki, N. Kamiya, S. Shiki, T.S. Kodama, A. Kakizuka, and H. Jingami Alpha,beta-unsaturated ketone is a core moiety of natural ligands for covalent binding to peroxisome proliferator-activated receptor gamma J. Biol. Chem. 280 2005 14145 14153
97. C. Schneider, D.A. Pratt, N.A. Porter, and A.R. Brash Control of oxygenation in lipoxygenase and cyclooxygenase catalysis Chem. Biol. 14 2007 473 488
98. H. Yin, and N.A. Porter New insights regarding the autoxidation of polyunsaturated fatty acids Antioxid. Redox Signal. 7 2005 170 184
99. Z. Yu, C. Schneider, W.E. Boeglin, L.J. Marnett, and A.R. Brash The lipoxygenase gene ALOXE3 implicated in skin differentiation encodes a hydroperoxide isomerase Proc. Natl. Acad. Sci. U. S. A. 100 2003 9162 9167
100. H. Kuhn Biosynthesis, metabolization and biological importance of the primary 15-lipoxygenase metabolites 15-hydro(pero)XY-5Z,8Z,11Z,13E-eicosatetraenoic acid and 13-hydro(pero)XY-9Z,11E-octadecadienoic acid Prog. Lipid Res. 35 1996 203 226
101. A.N. Baer, P.B. Costello, and F.A. Green Stereospecificity of the hydroxyeicosatetraenoic and hydroxyoctadecadienoic acids produced by cultured bovine endothelial cells Biochim. Biophys. Acta 1085 1991 45 52
102. S.M. Earles, J.C. Bronstein, D.L. Winner, and A.W. Bull Metabolism of oxidized linoleic acid: characterization of 13-hydroxyoctadecadienoic acid dehydrogenase activity from rat colonic tissue Biochim. Biophys. Acta 1081 1991 174 180
103. J. Capdevila, and W. Wang Role of cytochrome P450 epoxygenase in regulating renal membrane transport and hypertension Curr. Opin. Nephrol. Hypertens. 22 2013 163 169
104. V.Y. Ng, Y. Huang, L.M. Reddy, J.R. Falck, E.T. Lin, and D.L. Kroetz Cytochrome P450 eicosanoids are activators of peroxisome proliferator-activated receptor alpha Drug Metab. Dispos. 35 2007 1126 1134
105. V. Ng, and D.L. Kroetz Cytochrome P450 eicosanoids regulate fatty acid metabolism via PPAR alpha Clin. Pharmacol. Ther. 75 2004 P45-P45
106. D.H. Kim, L. Vanella, K. Inoue, A. Burgess, K. Gotlinger, V.L. Manthati, and et al. Epoxyeicosatrienoic acid agonist regulates human mesenchymal stem cell-derived adipocytes through activation of HO-1-pAKT signaling and a decrease in PPARgamma Stem Cells Dev. 19 2010 1863 1873
107. L. Vanella, D.H. Kim, K. Sodhi, I. Barbagallo, A.P. Burgess, J.R. Falck, and et al. Crosstalk between EET and HO-1 downregulates Bach1 and adipogenic marker expression in mesenchymal stem cell derived adipocytes Prostaglandins Other Lipid Mediat. 96 2011 54 62
108. W. Zha, M.L. Edin, K.C. Vendrov, R.N. Schuck, F.B. Lih, J.L. Jat, and et al. Functional characterization of cytochrome P450-derived epoxyeicosatrienoic acids (EETs) in adipogenesis and obesity J. Lipid Res. 2014
109. D.H. Kim, N. Puri, K. Sodhi, J.R. Falck, N.G. Abraham, J. Shapiro, and et al. Cyclooxygenase-2 dependent metabolism of 20-HETE increases adiposity and adipocyte enlargement in mesenchymal stem cell-derived adipocytes J. Lipid Res. 54 2013 786 793
110. 2 is a ligand for the adipocyte determination factor PPAR gamma Cell 83 1995 803 812
111. 2 metabolite binds peroxisome proliferator-activated receptor gamma and promotes adipocyte differentiation Cell 83 1995 813 819
112. 2 derivatives really playing the part? Cell. Signal. 14 2002 573 583
113. 2 and the ligation of PPARgamma J. Clin. Invest. 112 2003 945 955
114. 2 acting through PPARgamma-dependent and independent pathways Gene 505 2012 46 52
115. 2 synthesized by adipocytes during maturation phase contributes to upregulation of fat storage FEBS Lett. 580 2006 6885 6890
116. 2 and its application to the measurement of the endogenous product generated by cultured adipocytes during the maturation phase Prostaglandins Other Lipid Mediat. 94 2011 73 80
117. W.L. Chou, L.M. Chuang, C.C. Chou, A.H. Wang, J.A. Lawson, G.A. FitzGerald, and et al. Identification of a novel prostaglandin reductase reveals the involvement of prostaglandin E2 catabolism in regulation of peroxisome proliferator-activated receptor gamma activation J. Biol. Chem. 282 2007 18162 18172
118. D. Lu, C. Han, and T. Wu 15-Hydroxyprostaglandin dehydrogenase-derived 15-keto-prostaglandin E2 inhibits cholangiocarcinoma cell growth through interaction with peroxisome proliferator-activated receptor-gamma, SMAD2/3, and TAP63 proteins J. Biol. Chem. 288 2013 19484 19502
119. Y.H. Yu, Y.C. Chang, T.H. Su, J.Y. Nong, C.C. Li, and L.M. Chuang Prostaglandin reductase-3 negatively modulates adipogenesis through regulation of PPARgamma activity J. Lipid Res. 54 2013 2391 2399
120. B.T. Hyman, L.L. Stoll, and A.A. Spector Prostaglandin production by 3T3-L1 cells in culture Biochim. Biophys. Acta 713 1982 375 385
121. Y.H. Wu, T.P. Ko, R.T. Guo, S.M. Hu, L.M. Chuang, and A.H. Wang Structural basis for catalytic and inhibitory mechanisms of human prostaglandin reductase PTGR2 Structure 16 2008 1714 1723
122. D.A. Casimir, C.W. Miller, and J.M. Ntambi Preadipocyte differentiation blocked by prostaglandin stimulation of prostanoid FP2 receptor in murine 3T3-L1 cells Diff. Res. Biol. Divers. 60 1996 203 210
123. T. Inazumi, N. Shirata, K. Morimoto, H. Takano, E. Segi-Nishida, and Y. Sugimoto Prostaglandin E(2)-EP4 signaling suppresses adipocyte differentiation in mouse embryonic fibroblasts via an autocrine mechanism J. Lipid Res. 52 2011 1500 1508
124. L. Liu, and N.A. Clipstone Prostaglandin F2alpha inhibits adipocyte differentiation via a G alpha q-calcium-calcineurin-dependent signaling pathway J. Cell. Biochem. 100 2007 161 173
125. C.W. Miller, D.A. Casimir, and J.M. Ntambi The mechanism of inhibition of 3T3-L1 preadipocyte differentiation by prostaglandin F2alpha Endocrinology 137 1996 5641 5650
126. M.J. Reginato, S.L. Krakow, S.T. Bailey, and M.A. Lazar Prostaglandins promote and block adipogenesis through opposing effects on peroxisome proliferator-activated receptor gamma J. Biol. Chem. 273 1998 1855 1858
127. G. Serrero, and N.M. Lepak Prostaglandin F2alpha receptor (FP receptor) agonists are potent adipose differentiation inhibitors for primary culture of adipocyte precursors in defined medium Biochem. Biophys. Res. Commun. 233 1997 200 202
128. H. Tsuboi, Y. Sugimoto, T. Kainoh, and A. Ichikawa Prostanoid EP4 receptor is involved in suppression of 3T3-L1 adipocyte differentiation Biochem. Biophys. Res. Commun. 322 2004 1066 1072
129. X. Chu, K. Nishimura, M. Jisaka, T. Nagaya, F. Shono, and K. Yokota Up-regulation of adipogenesis in adipocytes expressing stably cyclooxygenase-2 in the antisense direction Prostaglandins Other Lipid Mediat. 91 2010 1 9
130. L. Madsen, L.M. Pedersen, H.H. Lillefosse, E. Fjaere, I. Bronstad, Q. Hao, and et al. UCP1 induction during recruitment of brown adipocytes in white adipose tissue is dependent on cyclooxygenase activity PLoS One 5 2010 e11391
131. A. Vegiopoulos, K. Muller-Decker, D. Strzoda, I. Schmitt, E. Chichelnitskiy, A. Ostertag, and et al. Cyclooxygenase-2 controls energy homeostasis in mice by de novo recruitment of brown adipocytes Science 328 2010 1158 1161
132. L. Fajas, S. Miard, M.R. Briggs, and J. Auwerx Selective cyclo-oxygenase-2 inhibitors impair adipocyte differentiation through inhibition of the clonal expansion phase J. Lipid Res. 44 2003 1652 1659
133. R.K. Petersen, C. Jorgensen, A.C. Rustan, L. Froyland, K. Muller-Decker, G. Furstenberger, and et al. Arachidonic acid-dependent inhibition of adipocyte differentiation requires PKA activity and is associated with sustained expression of cyclooxygenases J. Lipid Res. 44 2003 2320 2330
134. H. Yan, A. Kermouni, M. Abdel-Hafez, and D.C. Lau Role of cyclooxygenases COX-1 and COX-2 in modulating adipogenesis in 3T3-L1 cells J. Lipid Res. 44 2003 424 429
135. M. Kellinsalmi, V. Parikka, J. Risteli, T. Hentunen, H.V. Leskela, S. Lehtonen, and et al. Inhibition of cyclooxygenase-2 down-regulates osteoclast and osteoblast differentiation and favours adipocyte formation in vitro Eur. J. Pharmacol. 572 2007 102 110
136. M.G. Hossain, T. Iwata, N. Mizusawa, S.W. Shima, T. Okutsu, K. Ishimoto, and et al. Compressive force inhibits adipogenesis through COX-2-mediated down-regulation of PPARgamma2 and C/EBPalpha J. Biosci. Bioeng. 109 2010 297 303
137. J.T. Huang, J.S. Welch, M. Ricote, C.J. Binder, T.M. Willson, C. Kelly, and et al. Interleukin-4-dependent production of PPAR-gamma ligands in macrophages by 12/15-lipoxygenase Nature 400 1999 378 382
138. Q. Li, Y.P. Cheon, A. Kannan, S. Shanker, I.C. Bagchi, and M.K. Bagchi A novel pathway involving progesterone receptor, 12/15-lipoxygenase-derived eicosanoids, and peroxisome proliferator-activated receptor gamma regulates implantation in mice J. Biol. Chem. 279 2004 11570 11581
139. L. Nagy, P. Tontonoz, J.G. Alvarez, H. Chen, and R.M. Evans Oxidized LDL regulates macrophage gene expression through ligand activation of PPARgamma Cell 93 1998 229 240
140. S.B. Shappell, R.A. Gupta, S. Manning, R. Whitehead, W.E. Boeglin, C. Schneider, and et al. 15S-Hydroxyeicosatetraenoic acid activates peroxisome proliferator-activated receptor gamma and inhibits proliferation in PC3 prostate carcinoma cells Cancer Res. 61 2001 497 503
141. G. Shillabeer, V. Kumar, E. Tibbo, and D.C. Lau Arachidonic acid metabolites of the lipoxygenase as well as the cyclooxygenase pathway may be involved in regulating preadipocyte differentiation Metab. Clin. Exp. 47 1998 461 466
142. J.B. Hansen, R.K. Petersen, B.M. Larsen, J. Bartkova, J. Alsner, and K. Kristiansen Activation of peroxisome proliferator-activated receptor gamma bypasses the function of the retinoblastoma protein in adipocyte differentiation J. Biol. Chem. 274 1999 2386 2393
143. P. Hallenborg, C. Jorgensen, R.K. Petersen, S. Feddersen, P. Araujo, P. Markt, and et al. Epidermis-type lipoxygenase 3 regulates adipocyte differentiation and peroxisome proliferator-activated receptor gamma activity Mol. Cell. Biol. 30 2010 4077 4091
144. A. Brunnstrom, M. Hamberg, W.J. Griffiths, B. Mannervik, and H.E. Claesson Biosynthesis of 14,15-hepoxilins in human l1236 Hodgkin lymphoma cells and eosinophils Lipids 46 2011 69 79
145. Z. Yu, C. Schneider, W.E. Boeglin, and A.R. Brash Human and mouse eLOX3 have distinct substrate specificities: implications for their linkage with lipoxygenases in skin Arch. Biochem. Biophys. 455 2006 188 196
146. A.D. Dobrian, D.C. Lieb, Q. Ma, J.W. Lindsay, B.K. Cole, K. Ma, and et al. Differential expression and localization of 12/15 lipoxygenases in adipose tissue in human obese subjects Biochem. Biophys. Res. Commun. 403 2010 485 490
147. S. Dzitoyeva, H. Chen, and H. Manev 5-lipoxygenase-activating protein as a modulator of olanzapine-induced lipid accumulation in adipocyte J. Lipids 2013 2013 864593
148. I. Mothe-Satney, C. Filloux, H. Amghar, C. Pons, V. Bourlier, J. Galitzky, and et al. Adipocytes secrete leukotrienes: contribution to obesity-associated inflammation and insulin resistance in mice Diabetes 61 2012 2311 2319
149. Y. Kanda, T. Hinata, S.W. Kang, and Y. Watanabe Reactive oxygen species mediate adipocyte differentiation in mesenchymal stem cells Life Sci. 89 2011 250 258
150. Y. Li, S. Mouche, T. Sajic, C. Veyrat-Durebex, R. Supale, D. Pierroz, and et al. Deficiency in the NADPH oxidase 4 predisposes towards diet-induced obesity Int. J. Obes. 36 2012 1503 1513
151. K. Schroder, K. Wandzioch, I. Helmcke, and R.P. Brandes Nox4 acts as a switch between differentiation and proliferation in preadipocytes Arterioscler. Thromb. Vasc. Biol. 29 2009 239 245
152. S. Mouche, S.B. Mkaddem, W. Wang, M. Katic, Y.H. Tseng, S. Carnesecchi, and et al. Reduced expression of the NADPH oxidase NOX4 is a hallmark of adipocyte differentiation Biochim. Biophys. Acta 2007 1773 1015 1027
153. X. Lu, T.C. Murphy, M.S. Nanes, and C.M. Hart PPARγ regulates hypoxia-induced Nox4 expression in human pulmonary artery smooth muscle cells through NF-κB Am. J. Physiol. Lung Cell. Mol. Physiol. 299 2010 L559 L566
154. K.J. Cheung, I. Tzameli, P. Pissios, I. Rovira, O. Gavrilova, T. Ohtsubo, and et al. Xanthine oxidoreductase is a regulator of adipogenesis and PPARgamma activity Cell Metab. 5 2007 115 128
155. E.W. Kellogg 3rd, and I. Fridovich Superoxide, hydrogen peroxide, and singlet oxygen in lipid peroxidation by a xanthine oxidase system J. Biol. Chem. 250 1975 8812 8817
156. T.C. Pederson, and S.D. Aust The mechanism of liver microsomal lipid peroxidation Biochim. Biophys. Acta 385 1975 232 241
157. J. Hunt, and V. Massey Purification and properties of milk xanthine dehydrogenase J. Biol. Chem. 267 1992 21479 21485
158. P. Xu, T.P. Huecksteadt, and J.R. Hoidal Molecular cloning and characterization of the human xanthine dehydrogenase gene (XDH) Genomics 34 1996 173 180
159. N. Murakami, T. Ohtsubo, Y. Kansui, K. Goto, H. Noguchi, Y. Haga, and et al. Mice heterozygous for the xanthine oxidoreductase gene facilitate lipid accumulation in adipocytes Arterioscler. Thromb. Vasc. Biol. 34 2014 44 51
160. C. Vorbach, A. Scriven, and M.R. Capecchi The housekeeping gene xanthine oxidoreductase is necessary for milk fat droplet enveloping and secretion: gene sharing in the lactating mammary gland Genes Dev. 16 2002 3223 3235
161. D.M. Niedowicz, and D.L. Daleke The role of oxidative stress in diabetic complications Cell Biochem. Biophys. 43 2005 289 330
162. Z. Yu, C. Schneider, W.E. Boeglin, and A.R. Brash Epidermal lipoxygenase products of the hepoxilin pathway selectively activate the nuclear receptor PPARalpha Lipids 42 2007 491 497
163. Z. Yu, C. Schneider, W.E. Boeglin, and A.R. Brash Mutations associated with a congenital form of ichthyosis (NCIE) inactivate the epidermal lipoxygenases 12R-LOX and eLOX3 Biochim. Biophys. Acta 2005 1686 238 247
164. B.M. De Taeye, C. Morisseau, J. Coyle, J.W. Covington, A. Luria, J. Yang, and et al. Expression and regulation of soluble epoxide hydrolase in adipose tissue Obesity (Silver Spring) 18 2010 489 498
165. W. Wang, and N. Ballatori Endogenous glutathione conjugates: occurrence and biological functions Pharmacol. Rev. 50 1998 335 356
166. P.R. Devchand, H. Keller, J.M. Peters, M. Vazquez, F.J. Gonzalez, and W. Wahli The PPARalpha-leukotriene B4 pathway to inflammation control Nature 384 1996 39 43
167. R.P. Brun, P. Tontonoz, B.M. Forman, R. Ellis, J. Chen, R.M. Evans, and et al. Differential activation of adipogenesis by multiple PPAR isoforms Genes Dev. 10 1996 974 984
168. S.S. Lee, T. Pineau, J. Drago, E.J. Lee, J.W. Owens, D.L. Kroetz, and et al. Targeted disruption of the alpha isoform of the peroxisome proliferator-activated receptor gene in mice results in abolishment of the pleiotropic effects of peroxisome proliferators Mol. Cell. Biol. 15 1995 3012 3022
169. R. Nagaoka-Yasuda, N. Matsuo, B. Perkins, K. Limbaeck-Stokin, and M. Mayford An RNAi-based genetic screen for oxidative stress resistance reveals retinol saturase as a mediator of stress resistance Free Radic. Biol. Med. 43 2007 781 788
170. M. Schupp, M.I. Lefterova, J. Janke, K. Leitner, A.G. Cristancho, S.E. Mullican, and et al. Retinol saturase promotes adipogenesis and is downregulated in obesity Proc. Natl. Acad. Sci. U. S. A. 106 2009 1105 1110
171. A.R. Moise, G.P. Lobo, B. Erokwu, D.L. Wilson, D. Peck, S. Alvarez, and et al. Increased adiposity in the retinol saturase-knockout mouse FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol. 24 2010 1261 1270
172. M. Bouaboula, S. Hilairet, J. Marchand, L. Fajas, G. Le Fur, and P. Casellas Anandamide induced PPARgamma transcriptional activation and 3T3-L1 preadipocyte differentiation Eur. J. Pharmacol. 517 2005 174 181
173. R.B. Harris Direct and indirect effects of leptin on adipocyte metabolism Biochim. Biophys. Acta 2014 1842 414 423
174. M.P. Gonthier, L. Hoareau, F. Festy, I. Matias, M. Valenti, S. Bes-Houtmann, and et al. Identification of endocannabinoids and related compounds in human fat cells Obesity (Silver Spring) 15 2007 837 845
175. I. Matias, M.P. Gonthier, P. Orlando, V. Martiadis, L. De Petrocellis, C. Cervino, and et al. Regulation, function, and dysregulation of endocannabinoids in models of adipose and beta-pancreatic cells and in obesity and hyperglycemia J. Clin. Endocrinol. Metab. 91 2006 3171 3180
176. C. Silvestri, and V. Di Marzo The endocannabinoid system in energy homeostasis and the etiopathology of metabolic disorders Cell Metab. 17 2013 475 490
177. P.R. Baker, Y. Lin, F.J. Schopfer, S.R. Woodcock, A.L. Groeger, C. Batthyany, and et al. Fatty acid transduction of nitric oxide signaling: multiple nitrated unsaturated fatty acid derivatives exist in human blood and urine and serve as endogenous peroxisome proliferator-activated receptor ligands J. Biol. Chem. 280 2005 42464 42475
178. Y. Li, J. Zhang, F.J. Schopfer, D. Martynowski, M.T. Garcia-Barrio, A. Kovach, and et al. Molecular recognition of nitrated fatty acids by PPAR gamma Nat. Struct. Mol. Biol. 15 2008 865 867
179. F.J. Schopfer, Y. Lin, P.R. Baker, T. Cui, M. Garcia-Barrio, J. Zhang, and et al. Nitrolinoleic acid: an endogenous peroxisome proliferator-activated receptor gamma ligand Proc. Natl. Acad. Sci. U. S. A. 102 2005 2340 2345
180. P.R. Baker, F.J. Schopfer, S. Sweeney, and B.A. Freeman Red cell membrane and plasma linoleic acid nitration products: synthesis, clinical identification, and quantitation Proc. Natl. Acad. Sci. U. S. A. 101 2004 11577 11582
181. H. Yan, E. Aziz, G. Shillabeer, A. Wong, D. Shanghavi, A. Kermouni, and et al. Nitric oxide promotes differentiation of rat white preadipocytes in culture J. Lipid Res. 43 2002 2123 2129
182. B.A. Freeman, P.R. Baker, F.J. Schopfer, S.R. Woodcock, A. Napolitano, and M. d'Ischia Nitro-fatty acid formation and signaling J. Biol. Chem. 283 2008 15515 15519
183. R. Harrison Structure and function of xanthine oxidoreductase: where are we now? Free Radic. Biol. Med. 33 2002 774 797
184. V.B. O'Donnell, and B.A. Freeman Interactions between nitric oxide and lipid oxidation pathways: implications for vascular disease Circ. Res. 88 2001 12 21
185. T.M. McIntyre, A.V. Pontsler, A.R. Silva, A. St Hilaire, Y. Xu, J.C. Hinshaw, and et al. Identification of an intracellular receptor for lysophosphatidic acid (LPA): LPA is a transcellular PPARgamma agonist Proc. Natl. Acad. Sci. U. S. A. 100 2003 131 136
186. J.W. Newman, C. Morisseau, T.R. Harris, and B.D. Hammock The soluble epoxide hydrolase encoded by EPXH2 is a bifunctional enzyme with novel lipid phosphate phosphatase activity Proc. Natl. Acad. Sci. U. S. A. 100 2003 1558 1563
187. C. Morisseau, N.H. Schebb, H. Dong, A. Ulu, P.A. Aronov, and B.D. Hammock Role of soluble epoxide hydrolase phosphatase activity in the metabolism of lysophosphatidic acids Biochem. Biophys. Res. Commun. 419 2012 796 800
188. M.F. Simon, D. Daviaud, J.P. Pradere, S. Gres, C. Guigne, M. Wabitsch, and et al. Lysophosphatidic acid inhibits adipocyte differentiation via lysophosphatidic acid 1 receptor-dependent down-regulation of peroxisome proliferator-activated receptor gamma2 J. Biol. Chem. 280 2005 14656 14662
189. T. Tsukahara, R. Tsukahara, Y. Fujiwara, J. Yue, Y. Cheng, H. Guo, and et al. Phospholipase D2-dependent inhibition of the nuclear hormone receptor PPARgamma by cyclic phosphatidic acid Mol. Cell 39 2010 421 432
190. S.S. Davies, A.V. Pontsler, G.K. Marathe, K.A. Harrison, R.C. Murphy, J.C. Hinshaw, and et al. Oxidized alkyl phospholipids are specific, high affinity peroxisome proliferator-activated receptor gamma ligands and agonists J. Biol. Chem. 276 2001 16015 16023
191. I.J. Lodhi, L. Yin, A.P. Jensen-Urstad, K. Funai, T. Coleman, J.H. Baird, and et al. Inhibiting adipose tissue lipogenesis reprograms thermogenesis and PPARgamma activation to decrease diet-induced obesity Cell Metab. 16 2012 189 201
192. J.B. Kim, H.M. Wright, M. Wright, and B.M. Spiegelman ADD1/SREBP1 activates PPARgamma through the production of endogenous ligand Proc. Natl. Acad. Sci. U. S. A. 95 1998 4333 4337
193. N. Witte, M. Muenzner, J. Rietscher, M. Knauer, S. Heidenreich, A.M. Nuotio-Antar, and et al. The glucose sensor ChREBP links de-novo lipogenesis to PPARgamma activity and adipocyte differentiation Endocrinology 2015 EN20151209
194. M. Lafontan Historical perspectives in fat cell biology: the fat cell as a model for the investigation of hormonal and metabolic pathways Am. J. Physiol. Cell Physiol. 302 2012 C327 C359
195. W. Schmidt, G. Poll-Jordan, and G. Loffler Adipose conversion of 3T3-L1 cells in a serum-free culture system depends on epidermal growth factor, insulin-like growth factor I, corticosterone, and cyclic AMP J. Biol. Chem. 265 1990 15489 15495
196. Q.Q. Tang, T.C. Otto, and M.D. Lane Mitotic clonal expansion: a synchronous process required for adipogenesis Proc. Natl. Acad. Sci. U. S. A. 100 2003 44 49
197. J.J. Tomlinson, A. Boudreau, D. Wu, E. Atlas, and R.J. Hache Modulation of early human preadipocyte differentiation by glucocorticoids Endocrinology 147 2006 5284 5293
198. Y.C. Cho, and C.R. Jefcoate PPARgamma1 synthesis and adipogenesis in C3H10T1/2 cells depends on S-phase progression, but does not require mitotic clonal expansion J. Cell. Biochem. 91 2004 336 353
199. D. Prusty, B.H. Park, K.E. Davis, and S.R. Farmer Activation of MEK/ERK signaling promotes adipogenesis by enhancing peroxisome proliferator-activated receptor gamma (PPARgamma) and C/EBPalpha gene expression during the differentiation of 3T3-L1 preadipocytes J. Biol. Chem. 277 2002 46226 46232
200. P. Hallenborg, R.K. Petersen, S. Feddersen, U. Sundekilde, J.B. Hansen, B. Blagoev, and et al. PPARgamma ligand production is tightly linked to clonal expansion during initiation of adipocyte differentiation J. Lipid Res. 55 2014 2491 2500
201. G.S. van Rossum, A.S. Vlug, H. van den Bosch, A.J. Verkleij, and J. Boonstra Cytosolic phospholipase A(2) activity during the ongoing cell cycle J. Cell. Physiol. 188 2001 321 328
202. 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. 279 2004 21740 21748
203. J. Boonstra, and G.S. van Rossum The role of cytosolic phospholipase A2 in cell cycle progression Prog. Cell Cycle Res. 5 2003 181 190
204. R.K. Petersen, L. Madsen, L.M. Pedersen, P. Hallenborg, H. Hagland, K. Viste, and et al. Cyclic AMP (cAMP)-mediated stimulation of adipocyte differentiation requires the synergistic action of Epac- and cAMP-dependent protein kinase-dependent processes Mol. Cell. Biol. 28 2008 3804 3816
205. M. Elizalde, M. Ryden, V. van Harmelen, P. Eneroth, H. Gyllenhammar, C. Holm, and et al. Expression of nitric oxide synthases in subcutaneous adipose tissue of nonobese and obese humans J. Lipid Res. 41 2000 1244 1251
206. J.W. Choi, S.H. Pai, S.K. Kim, M. Ito, C.S. Park, and Y.N. Cha Increases in nitric oxide concentrations correlate strongly with body fat in obese humans Clin. Chem. 47 2001 1106 1109
207. S.P. Weisberg, D. McCann, M. Desai, M. Rosenbaum, R.L. Leibel, and A.W. Ferrante Jr. Obesity is associated with macrophage accumulation in adipose tissue J. Clin. Invest. 112 2003 1796 1808
208. 2 Am. J. Physiol. Cell Physiol. 301 2011 C1360 C1367
209. G. Ferry, E. Tellier, A. Try, S. Gres, I. Naime, M.F. Simon, and et al. Autotaxin is released from adipocytes, catalyzes lysophosphatidic acid synthesis, and activates preadipocyte proliferation. Up-regulated expression with adipocyte differentiation and obesity J. Biol. Chem. 278 2003 18162 18169
210. M. Kanehisa, and S. Goto KEGG: Kyoto Encyclopedia of Genes and Genomes Nucleic Acids Res. 28 2000 27 30
211. M. Kanehisa, S. Goto, Y. Sato, M. Kawashima, M. Furumichi, and M. Tanabe Data, information, knowledge and principle: back to metabolism in KEGG Nucleic Acids Res. 42 2014 D199 D205
212. P. Shannon, A. Markiel, O. Ozier, N.S. Baliga, J.T. Wang, D. Ramage, and et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks Genome Res. 13 2003 2498 2504