29. Granneman JG, Li P, Zhu Z, Lu Y (2005) Metabolic and cellular plasticity in white adipose tissue I: effects of beta3-adrenergic receptor activation. Am J Physiol Endocrinol Metab 289: E608–E616. 30. Petrovic N, Walden TB, Shabalina IG, Timmons JA, Cannon B, et al. (2009) Chronic PPARc Activation of Epididymally Derived White Adipocyte Cultures Reveals a Population of Thermogenically Competent, UCP1-containing Adipocytes Molecularly Distinct From Classical Brown Adipocytes. J Biol Chem Dec 22. [Epub ahead of print]. 31. Guerra C, Koza RA, Yamashita H, Walsh K, Kozak LP (1998) Emergence of Brown Adipocytes in White Fat in Mice Is Under Genetic Control. Effects on Body Weight and Adiposity. J Clin Invest 102: 412–420. 32. Watson PM, Commins SP, Beiler RJ, Hatcher HC, Gettys TW (2000) Differential regulation of leptin expression and function in A/J vs. C57BL/6J mice during diet-induced obesity. Am J Physiol Endocrinol Metab 279: E356–E365. 33. Kopecky J, Rossmeisl M, Hodny Z, Syrovy I, Horakova M, et al. (1996) Reduction of dietary obesity in aP2-Ucp transgenic mice: mechanism and adipose tissue morphology. Am J Physiol Endocrinol Metab 270: E776–E786. 34. Oberkofler H, Dallinger G, Liu YM, Hell E, Krempler F, et al. (1997) Uncoupling protein gene: quantification of expression levels in adipose tissues of obese and non-obese humans. J Lipid Res 38: 2125–2133. 35. Semple RK, Crowley VC, Sewter CP, Laudes M, Christodoulides C, et al. (2003) Expression of the thermogenic nuclear hormone receptor coactivator PGC-1[alpha] is reduced in the adipose tissue of morbidly obese subjects. Int J Obes Relat Metab Disord 28: 176–179. 36. Jimenez M, Barbatelli G, Allevi R, Cinti S, Seydoux J, et al. (2003) b3 - Adrenoceptor knockout in C57BL/6J mice depresses the occurrence of brown adipocytes in white. European Journal of Biochemistry 270: 699–705. 37. Grujic D, Susulic VS, Harper ME, Himms-Hagen J, Cunningham BA, et al. (1997) beta 3-Adrenergic Receptors on White and Brown Adipocytes Mediate beta 3-Selective Agonist-induced Effects on Energy Expenditure, Insulin Secretion, and Food Intake. J Biol Chem 272: 17686–17693. 38. Gaskins HD, Hausman DB, Martin RJ, Hausman GJ (1989) Evidence for abnormal prostaglandin synthesis in obese Zucker rat adipose cell cultures. J Nutr 119: 458–462. 39. Madsen L, Pedersen LM, Liaset B, Ma T, Petersen RK, et al. (2008) cAMP- dependent Signaling Regulates the Adipogenic Effect of n-6 Polyunsaturated Fatty Acids. J Biol Chem 283: 7196–7205. 40. Petersen RK, Jorgensen C, Rustan AC, Froyland L, Muller-Decker K, et al. (2003) Arachidonic acid-dependent inhibition of adipocyte differentiation requires PKA activity and is associated with sustained expression of cyclooxygenases. J Lipid Res 44: 2320–2330. 41. Vassaux G, Gaillard D, Darimont C, Ailhaud G, Negrel R (1992) Differential response of preadipocytes and adipocytes to prostacyclin and prostaglandin E2: physiological implications. Endocrinology 131: 2393–2398. 42. Cinti S (2009) Transdifferentiation properties of adipocytes in the Adipose Organ. Am J Physiol Endocrinol Metab: 00183. 43. Hansen JB, Jorgensen C, Petersen RK, Hallenborg P, De Matteis R, et al. (2004) Retinoblastoma protein functions as a molecular switch determining white versus brown adipocyte differentiation. Proc Natl Acad Sci U S A 101: 4112–4117. 44. Hansen JB, Jorgensen C, Petersen RK, Hallenborg P, De Matteis R, et al. (2004) Retinoblastoma protein functions as a molecular switch determining white versus brown adipocyte differentiation. Proc Natl Acad Sci U S A 101: 4112–4117. 45. Hyman BT, Stoll LL, Spector AA (1982) Prostaglandin production by 3T3-L1 cells in culture. Biochim Biophys Acta 713: 375–385. 46. Madsen L, Pedersen LM, Liaset B, Ma T, Petersen RK, et al. (2008) cAMP- dependent Signaling Regulates the Adipogenic Effect of n-6 Polyunsaturated Fatty Acids. J Biol Chem 283: 7196–7205. 47. Tseng YH, Kokkotou E, Schulz TJ, Huang TL, Winnay JN, et al. (2008) New role of bone morphogenetic protein 7 in brown adipogenesis and energy expenditure. Nature 454: 1000–1004. 48. Fain JN, Ballou LR, Bahouth SW (2001) Obesity is induced in mice heterozygous for cyclooxygenase-2. Prostaglandins Other Lipid Mediat 65: 199–209. 49. Morham SG, Langenbach R, Loftin CD, Tiano HF, Vouloumanos N, et al. (1995) Prostaglandin synthase 2 gene disruption causes severe renal pathology in the mouse. Cell 83: 473–482. 50. Ushikubi F, Hirata M, Narumiya S (1995) Molecular biology of prostanoid receptors: an overview. J Lipin Mediat 12: 343–359. 51. Abramovitz M, Adam M, Boie Y, Carrie`re MC, Denis D, et al. (2000) The utilization of recombinant prostanoid receptors to determine the affinities and selectivities of prostaglandins and related analogs. Biochimica et Biophysica Acta 1483: 285–293. 52. Kunikata T, Tanaka A, Miyazawa T, Kato S, Takeuchi K (2002) 16,16- Dimethyl Prostaglandin E2 Inhibits Indomethacin-Induced Small Intestinal Lesions Through EP3 and EP4 Receptors. Digestive Diseases and Sciences 47: 894–904. 53. Koza RA, Hohmann SM, Guerra C, Rossmeisl M, Kozak LP (2000) Synergistic Gene Interactions Control the Induction of the Mitochondrial Uncoupling Protein (Ucp1) Gene in White Fat Tissue. J Biol Chem 275: 34486–34492. Cyclooxygenases and UCP1 54. Guerra C, Koza RA, Yamashita H, Walsh K, Kozak LP (1998) Emergence of Brown Adipocytes in White Fat in Mice Is Under Genetic Control. Effects on Body Weight and Adiposity. J Clin Invest 102: 412–420. 55. Collins S, Daniel KW, Petro AE, Surwit RS (1997) Strain-Specific Response to b3-Adrenergic Receptor Agonist Treatment of Diet-Induced Obesity in Mice. Endocrinology 138: 405–413. 56. Guerra C, Koza RA, Yamashita H, Walsh K, Kozak LP (1998) Emergence of Brown Adipocytes in White Fat in Mice Is Under Genetic Control. Effects on Body Weight and Adiposity. J Clin Invest 102: 412–420. 57. Watson PM, Commins SP, Beiler RJ, Hatcher HC, Gettys TW (2000) Differential regulation of leptin expression and function in A/J vs. C57BL/6J mice during diet-induced obesity. Am J Physiol Endocrinol Metab 279: E356–E365. 58. Feldmann HM, Golozoubova V, Cannon B, Nedergaard J (2009) UCP1 Ablation Induces Obesity and Abolishes Diet-Induced Thermogenesis in Mice Exempt from Thermal Stress by Living at Thermoneutrality. Cell Metabolism 9: 203–209. 59. Rothwell NJ, Stock MJ (1979) A role for brown adipose tissue in diet-induced thermogenesis. Nature 281: 31–35. 60. Enerba¨ck S, Jacobsson A, Simpson EM, Guerra C, Yamashita H, et al. (1997) Mice lacking mitochondrial uncoupling protein are cold-sensitive but not obese. Nature 387: 90–94. 61. Feldmann HM, Golozoubova V, Cannon B, Nedergaard J (2009) UCP1 Ablation Induces Obesity and Abolishes Diet-Induced Thermogenesis in Mice Exempt from Thermal Stress by Living at Thermoneutrality. Cell Metabolism 9: 203–209. 62. Madsen L, Pedersen LM, Liaset B, Ma T, Petersen RK, et al. (2008) cAMP- dependent Signaling Regulates the Adipogenic Effect of n-6 Polyunsaturated Fatty Acids. J Biol Chem 283: 7196–7205. 63. Stenbit AE, Tsao TS, Li J, Burcelin R, Geenen DL, et al. (1997) GLUT4 heterozygous knockout mice develop muscle insulin resistance and diabetes. Nat Med 3: 1096–1101. 64. Hetu PO, Riendeau D (2007) Down-regulation of Microsomal Prostaglandin E2 Synthase-1 in Adipose Tissue by High-fat Feeding. Obesity Res 15: 60–68. 65. Sakuma Y, Tanaka K, Suda M, Komatsu Y, Yasoda A, et al. (2000) Impaired Bone Resorption by Lipopolysaccharide In Vivo in Mice Deficient in the Prostaglandin E Receptor EP4 Subtype. Infect Immun 68: 6819–6825. 66. Jimenez M, Barbatelli G, Allevi R, Cinti S, Seydoux J, et al. (2003) b3 - Adrenoceptor knockout in C57BL/6J mice depresses the occurrence of brown adipocytes in white. European Journal of Biochemistry 270: 699–705. 67. Leonardsson G, Steel JH, Christian M, Pocock V, Milligan S, et al. (2004) Nuclear receptor corepressor RIP140 regulates fat accumulation. Proc Natl Acad Sci U S A 101: 8437–8442. 68. Razani B, Combs TP, Wang XB, Frank PG, Park DS, et al. (2002) Caveolin-1- deficient mice are lean, resistant to diet-induced obesity, and show hypertri- glyceridemia with adipocyte abnormalities. J Biol Chem 277: 8635–8647. 69. Toh SY, Gong J, Du G, Li JZ, Yang S, et al. (2008) Up-Regulation of Mitochondrial Activity and Acquirement of Brown Adipose Tissue-Like Property in the White Adipose Tissue of Fsp27 Deficient Mice. PLoS ONE 3: e2890. 70. Stro¨m K, Hansson O, Lucas S, Nevsten P, Fernandez C, et al. (2008) Attainment of Brown Adipocyte Features in White Adipocytes of Hormone- Sensitive Lipase Null Mice. PLoS ONE 3: e1793. 71. Narvaez CJ, Matthews D, Broun E, Chan M, Welsh J (2009) Lean Phenotype and Resistance to Diet-Induced Obesity in Vitamin D Receptor Knockout Mice Correlates with Induction of Uncoupling Protein-1 in White Adipose Tissue. Endocrinology 150: 651–661. 72. Cummings DE, Brandon EP, Planas JV, Motamed K, Idzerda RL, et al. (1996) Genetically lean mice result from targeted disruption of the RII[beta] subunit of protein kinase A. Nature 382: 622–626. 73. Hansen JB, Jorgensen C, Petersen RK, Hallenborg P, De Matteis R, et al. (2004) Retinoblastoma protein functions as a molecular switch determining white versus brown adipocyte differentiation. Proc Natl Acad Sci U S A 101: 4112–4117. 74. Cederberg A, Gronning LM, Ahren B, Tasken K, Carlsson P, et al. (2001) FOXC2 Is a Winged Helix Gene that Counteracts Obesity, Hypertriglyceride- mia, and Diet-Induced Insulin Resistance. Cell 106: 563–573. 75. Kopecky J, Rossmeisl M, Hodny Z, Syrovy I, Horakova M, et al. (1996) Reduction of dietary obesity in aP2-Ucp transgenic mice: mechanism and adipose tissue morphology. Am J Physiol Endocrinol Metab 270: E776–E786. 76. Kopecky J, Rossmeisl M, Hodny Z, Syrovy I, Horakova M, et al. (1996) Reduction of dietary obesity in aP2-Ucp transgenic mice: mechanism and adipose tissue morphology. Am J Physiol Endocrinol Metab 270: E776–E786. 77. Guerra C, Koza RA, Yamashita H, Walsh K, Kozak LP (1998) Emergence of Brown Adipocytes in White Fat in Mice Is Under Genetic Control. Effects on Body Weight and Adiposity. J Clin Invest 102: 412–420. 78. Watson PM, Commins SP, Beiler RJ, Hatcher HC, Gettys TW (2000) Differential regulation of leptin expression and function in A/J vs. C57BL/6J mice during diet-induced obesity. Am J Physiol Endocrinol Metab 279: E356–E365. 79. Oberkofler H, Dallinger G, Liu YM, Hell E, Krempler F, et al. (1997) Uncoupling protein gene: quantification of expression levels in adipose tissues of obese and non-obese humans. J Lipid Res 38: 2125–2133. PLoS ONE | www.plosone.org 12 June 2010 | Volume 5 | Issue 6 | e11391