Adipogenesis and obesity: Rounding out the big picture

Cell

Volumn 87, Issue 3, 1996, Pages 377-389

  Spiegelman, Bruce M ^a   Flier, Jeffrey S ^a  

^a HARVARD MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ADIPOCYTE; ADIPOSE TISSUE; CELL DIFFERENTIATION; ENERGY BALANCE; FOOD INTAKE; GENETIC LINKAGE; HUMAN; NONHUMAN; OBESITY; PRIORITY JOURNAL; REVIEW; SIGNAL TRANSDUCTION; TRANSCRIPTION REGULATION;

EID: 0030297919     PISSN: 00928674     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0092-8674(00)81359-8     Document Type: Review

References (112)

1. Abbott, W.G., and Foley, J.E. (1987). Comparison of body composition, adipocyte size and glucose and insulin concentrations in Pima Indian and Caucasian children. Metabolism 36, 576-579.
2. Ahima, R.S., Prabakaran, D., Mantzoros, C., Qu, D., Lowell B., Maratos-Flier, E., and Flier, J.S. (1996). Role of leptin in the neuroendocrine response to fasting. Nature 382, 250-252.
3. Arase, K., York, D.A., Shimizu, H., Shargill, N., and Bray, G.A. (1988). Effects of corticotropin-releasing factor on food intake and brown adipose tissue thermogenesis in rats. Am. J. Physiol. 255, E255-259.
4. Banks, W.A., Kastin, A.J., Huang, W., Jaspan, J.B., and Maness, L.M. (1996). Leptin enters the brain by a saturable system independent of insulin. Peptides 17, 305-311.
5. Billington, C.J., Briggs, J.E., Grace, M., and Levine, A.S. (1991). Effects of intracerebroventricular injection of neuropeptide Y on energy metabolism. Am. J. Physiol. 260, R321-327.
6. Bouchard, C. (1995). Genetics of obesity: an update on molecular markers. Int. J. Obesity 19, S10-13.
7. Bray, G.A., Fisler, J., and York, D.A. (1990). Neuroendocrine Control of the development of obesity: understanding gained from studies of experimental animal models. Front. Neuroendocrinol. 11, 128-181.
8. Brun, R.P., Tontonoz, P., Forman, B.M., Ellis, R., Chen, J., Evans, R.M., and Spiegelman, B.M. (1996). Differential activation of adipogenesis by multiple PPAR isoforms. Genes Dev. 10, 974-984.
9. Bultman, S., Michaud, E., and Woychik, R. (1992). Molecular characterization of the mouse agouti locus. Cell 71, 1195-1204.
10. Bunone, G., Briand, P.-A., Miksicek, R.J., and Picard, D. (1996). Activation of the unliganded estrogen receptor by EGF involves the MAP kinase pathway of direct phosphorylation. EMBO J. 15, 2174-2183.
11. Campfield, L., Smith, F., Guisez, Y., Devos, R., and Burn, P. (1995). Recombinant mouse OB protein: Evidence for a peripheral signal linking adiposity and central neural networks. Science 269, 546-548.
12. Caro, J.F., Kolaczynski, J.W., Nyce, M.R., Ohannesian, J.P. Opentanova, I., Goldman, W.H., Lynn, R.R., Zhang, P.L., Sinha, M.K., and Considine, R.V. (1996). Decreased cerebrospinal-fluid/serum leptin ratio in obesity: a possible mechanism for leptin resistance. Lancet. 348, 159-161.
13. Chehab, F.F., Lim, M.E., and Lu, R (1996). Correction of the sterility defect in homozygous obese female mice by treatment with the human recombinant leptin. Nature Genet. 12, 318-320.
14. Chen, H., Charlat, O., Tartaglia, L.A., Woolf, E.A., Weng, X., Ellis, S. J., Lakey, N.D., Culpepper, J., Moore, K.J., Breitbart, R.E., Duyk, G. M., Tepper, R.I., and Morgenstern, J.P. (1996). Evidence that the diabetes gene encodes the leptin receptor: Identification of a mututation in the leptin receptor gene in db/db mice. Cell 84, 491-495.
15. Chua, S., Jr., White, D., Wu-Peng, Z., Liu, S., Okada, N., Kershaw, E., Tartaglia, L., and Leibel, R. (1996). Phenotype of fatty due to Gn269 Pro mutation in the Leptin Receptor (Lepr). Diabetes 45, 1141-1143.
16. Clement, K., Viasse, C., Manning, B.S., Basdeant, A., Guy-Grand, B., Ruiz, J., Silver, K.D., Shuldiner, A.R., Froguel, P., and Strosberg, A. D. (1995a). Genetic variation in the beta3-adrenergic receptor and an increased capacity to gain weight in patients with morbid obesity. N. Engl. J. Med. 333, 352-354.
17. Clement, K., Garner, C., Hager, J., Philippi, A., Due, C.L., Carey, A., Harris, T., and Jury, C. (1996). Indication for linkage of the human ob gene region with extreme obesity. Diabetes 45, 687-90.
18. Clement, K., Philippi, A., Jury, C., Pivdal, R., Hager, J., Demenais, F., Basdevant, A., and Guy-Grand, B. (1996a). Candidate gene approach of familial morbid obesity-linkage analysis of the glucocorticoid receptor gene. Int. J. Obesity 20, 507-512.
19. Coleman D. L., and Eicher, E.M. (1990). Fat (fat) and tubby (tub): two autosomal recessive mutations causing obesity syndromes in the mouse. J. Hered. 88, 424-427.
20. Collins, S., Kuhn, C., Petro, A., Swick, A., Chrunyk, B., and Surwit, R. (1996). Role of leptin in fat regulation. Nature 380, 677.
21. Considine, R., Sinha, M., Heiman, M., Kriauciunas, A., Stephens, T., Nyce, M., Ohannesian, J., and Marco, C. (1995). Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N. Engl. J. Med. 334, 292-295.
22. Considine, R., Considine, E., Williams, C., Nyce, N., Magosin, S., Bauer, T., Rosato, E., and Colberg, J. (1995). Evidence against either a premature stop codon of the absence of obese gene mRNA in human obesity. J. Clin. Invest. 95, 2986-2988.
23. Considine, R.V., Considine, E.L., Williams, C.J., Hyde, T.M., and Caro, J. F. (1996). The Hypothalamic leptin receptor in humans. Diabetes. 19, 992-994.
24. Deriaz, O., Dionne, F., Perusse, L., Tremblay, A., Vohl, M.C., Cote, G., and Bouchard, C. (1994). DNA variation in the genes of the Na, K-adenosine triphosphataseand its relation with resting metabolic rate, respiratory quotient, and body fat. J. Clin. Invest. 93, 838-843.
25. Dryden, S., Frankish, H., Wang, Q., and Williams, G. (1994). Neuropeptide Y and energy balance: one way ahead for the treatment of obesity? Eur. J. Clin. Invest. 24, 293-308.
26. Duggirala R, Stern, M., Mitchell, L., Reinhart, P., Uresandi, O., Leibel, R., and Hales, C. (1996). Quantitative variation in obesity related traits and insulin precursers linked to ob gene region on human chromosome 7. Am. J. Hum. Genet., in press.
27. Erickson, J., Clegg, K., and Palmiter, R. (1996). Sensitivity to leptin and susceptibility to seizures of mice lacking neuropeptide Y. Nature 381, 415-418.
28. Flier, J.S., Cook, K.S., Usher, P., and Spiegelman, B.M. (1987). Severely impaired adipsin expression in genetic and acquired obesity. Science 237, 405-408.
29. Forman, B.M., Tontonoz, P., Chen, J., Brun, R.P., Spiegelman, B.M., and Evans, R.M. (1995). 15-Deoxy-D12,14-Prostaglandin J2 is a ligand for the adipocyte determination factor PPARγ. Cell 83, 803-812.
30. Frederich, R.C., Jr., Kahn, B.B., Peach, M.J., and Flier, J.S. (1992). Tissue-specific nutritional regulation of angiotensinogen in adipose tissue. Hypertension 19, 339-344.
31. Frederich, R.C., Löllmann, B., Hamann, A., Napolitano-Rosen, A., Kahn, B. B., Lowell, B.B., and Flier, J.S. (1995). Expression of ob mRNA and its encoded protein in rodents: Impact of nutrition and obesity. J. Clin. Invest. 96, 1658-1663.
32. Frederich R., Hamann, A., Anderson, S., Löllmann, B., Lowell, B., and Flier, J. (1995a). Leptin levels reflect body lipid content in mice: evidence for diet-induced resistance to leptin action. Nature Med. 1, 1311-1314.
33. Freytag, S.O., Paielli, D.L., and Gilbert, J.D. (1994). Ectopic expression of the CCAAT/enhancer-binding protein a promotes the adipogenic program in a variety of mouse fibroblastic cells. Genes Dev. 8, 1654-1663.
34. Gerald, C., Walker, M., Criscione, L., Gustafson, E.I., Batzl-Hartman, C., Smith, K., Vaysse, P., and Durkin, M. (1996). A receptor subtype involved in neuropeptide-Y-induced food intake. Nature 382, 168-170.
35. Ghilardi, N., Ziegler, S., Wiestner, A., Stoffel, R., Heim, M.H., and Skoda, R.C. (1996). Defective STAT signaling by the leptin receptor in diabetic mice. Proc. Natl. Acad. Sci. USA 93, 6231-6235.
36. Green, S., and Wahli, W. (1994). Peroxisome proliferator-activated receptors: finding the orphan a home. Mol. Cell. Endocrinol. 100, 149-153.
37. Grunfeld, C., Zhao, C., Fuller, J., Pollack, A., Moser, A., Friedman, J., and Feingold, K.R. (1996). Endotoxin and cytokines induce expression of leptin, the ob gene product, in hamsters. J. Clin. Invest. 97, 2151-2157.
38. Halaas, J., Gajiwala, K., Maffei, M., Cohen, S., Chait, B., Rabinowitz, D., Lallone, R., and Burley, S. (1995). Weight reducing effects of the plasma protein encoded by the ob gene. Science 269, 543-546.
39. Harris, P.K., and Kletzien, R.F. (1994). Localization of a pioglitazone response element in the adipocyte fatty acid-binding protein gene. Mol. Pharmacol. 45, 439-445.
40. He, Y., Chen, H., Quon, M.J., and Reitman, M. (1995). The mouse obese gene. Genomic organization, promoteractivity, and activation by CCAAT/enhancer-binding protein alpha. J. Biol. Chem. 270, 28887-28891.
41. Hofmann, C., Lorenz, K., Braithwaite, S.S., Colca, J.R., Palzauk, B. J. J. R., Hotamisligil, G.S., and Spiegelman, B.M. (1994). Altered gene expression for tumor necrosis factor-a and its receptors during drug dietary modulation of insulin resistance. Endocrinology. 134, 264-270.
42. Hotamisligil, G.S., Peraldi, P, and Spiegelman, B.M. (1996). The molecular link between obesity and diabetes. Curr. Opin. Endocrin. Diabetes 3, 16-23.
43. Hu, E., Tontonoz, P., and Spiegelman, B.M. (1995). Transdifferentiation of myoblasts by the adipogenic transcription factors PPARγ and C/EBPα. Proc. Natl. Acad. Sci. USA 92, 9856-9860.
44. Hwang, C.S., Mandrup, S., MacDougald, O.A., Geiman, D.E., and Lane, M.D. (1996). Transcriptional activation of the mouse obese (ob) gene by CCAAT/enhancer binding protein alpha. Proc. Natl. Acad. Sci. USA. 93, 873-877.
45. Ibrahimi, A., Teboul, L., Gaillard, D., Amri, E.Z., Ailhaud, G., Young, P., Cawthorne, M.A., and Grimaldi, P.A. (1994). Evidence for a common mechanisms of action for fatty acids and thiazoldinedione antidiabetic agents on gene expression in preadipose cells. Mol. Pharmacol. 46, 1070-1076.
46. Jezek, P., Orosz, D.E., Modriansky, M., and Garlid, K.D. (1994). Transport of anions and protons by the mitochondrial uncoupling protein and its regulation by nucleotides and fatty acids. A new look at old hypotheses. J. Biol. Chem. 269, 26184-26190.
47. Kallen, C.B., and Lazar, M. (1996). Antidiabetic thiazolidinediones inhibit leptin (ob) gene expression in 3T3-L1 adipocytes. Proc. Natl. Acad. Sci. USA 93, 5793-5796.
48. Kim, J.B., Spotts, G.D., Halvorsen, Y.D., Shih, H.M., Ellenberger, T., Towle, H.C., and Spiegelman, B.M. (1995). Dual DNA binding specificity of ADD1/SREBP1 controlled by a single amino acid in the basic helix-loop-helix domain. Mol. Cell. Biol. 15, 2582-2588.
49. Kim, J.B., and Spiegelman, B.M. (1996). ADD1/SREBP1 promotes adipocyte differentiation and gene expression linked to fatty acid metabolism. Genes Dev. 10, 1096-1107.
50. Kletzien, R.F., Clarke, S.D., and Ulrich, R.G. (1992). Enhancement of adipocyte differentiation by an insulin-sensitizing agent. Mol. Pharmacol. 41, 393-398.
51. Kleyn, P.W., Fan, W., Kovats, S.G., Lee, J.J, Pulido, J.C., Wu, Y., Berkemeir, L.R., Misumi, D.J., Holmgren, L., Charlat, O., Woolf, E.A., Tayber, O., Brody, T., Shu, P., Hawkins, F., Kennedy, B., Baldini, L., Ebeling, C., Alperin, G.D., Deeds, J., Lakey, N.D., Culpepper, J., Chen, H., Alexandra Glucksmann-Kuis, M., Carlson, G.A., Duyk, G.M., and Moore, K. J. (1996). Identification and Characterization of the Mouse Obesity Gene tubby: A Member of a Novel Gene Family. Cell 85, 281-290.
52. Kliewer, S.A., Lenhard, J.M., Willson, T.M., Patel, I., Morris, D.C., and Lehmann, J.M. (1995). A prostaglandin J2 metabolite binds peroxisome proliferator-activated receptor gamma and promotes adipocyte differentiation. Cell 83, 813-819.
53. Lee, G.H., Proenca, R. Montez, J. M., Carroll, K.M., Darvishzadeh, J.G., Lee, J.I., and Friedman, J.M. (1996). Abnormal splicing of the leptin receptor in diabetic mice. Nature 379, 632-635.
54. Lehmann, J.M., Moore, L.B., Smith-Oliver, T.A., Wilkison, W.O., Willson, T. M., and Kliewer, S.A. (1995). An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-activated receptor γ. J. Biol. Chem. 270, 12953-12956.
55. Lowell, B.B., S-Susulic, V., Hamann, A., Lawitts, J.A., Himms-Hagen, J., Boyer, B.B., Kozak, L.P., and Flier, J.S. (1993). Development of obesity in transgenic mice following the genetic ablation of brown adipose tissue. Nature. 366, 740-743.
56. Lowell, B.B., and Flier, J.S. (1996). Brown adipose tissue, beta3-adrenergic receptors and obesity. Ann. Rev. Medicine, in press.
57. Lu, D., Willard, D., Patel, I.R., Kadwell, S., Overton, L., Kost, T., Luther, M., Chen, W., Woychik, R.P., Wilkison, W.O., and Cone, R.D. (1994). Agouti protein is an antagonist of the melanocyte-stimulating-hormone receptor. Nature 371, 799-802.
58. MacDougald, O.A., and Lane, M.D. (1995). Transcriptional regulation of gene expression during adipocyte differentiation. Annu. Rev. Biochem. 64, 345-373.
59. MacDougald, O.A., Hwang, C.S., Fan, H., and Lane, M.D. (1995a). Regulated expression of the obese gene product (leptin) in white adipose tissue and 3T3-L1 adipocytes. Proc. Natl. Acad. USA 92, 9034-9037.
60. MacDougald, O.A., Cornelius, T., Liu, R., and Lane, M.D. (1995b). Insulin regulates transcription of the CCAAT/enhancer binding proteins (C/EBP) alpha, beta, and delta genes in fully-differentiated 3T3-L1 adipocytes. J. Biol. Chem. 270, 647-654.
61. Maffei, M., Halaas, J., Ravussin, E., Pratley, R.E., Lee, G.H., Zhang, Y., Fei, H., Kim, S., Lallone, R., Ranganathan, S., Kern, P.S., and Friedman, J.M. (1995). Leptin levels in human and rodent: Measurement of plasma leptin and ob RNA in obese and weight-reduced subjects. Nature Med. 1, 1155-1161.
62. Maffei, M., Stoffel, M., Barone, M., Moon, B., Dammerman, M., Ravussin, E., Bogardus, C., Ludwig, D.S., Flier, J.S., Talley, M., Auerbach, S., and Friedman, J.M. (1996). Absence of mutations in the human OB gene in obese/diabetic subjects. Diabetes 45, 679-682.
63. Manne, J., Argeson, A.C., and Sirocusa, L.D. (1995). Mechanisms for the pleitropic effects of the agouti gene. Proc. Natl. Acad. Sci. USA 92, 4721-4724.
64. Mantzoros, C.S., Qu, D., Frederich, R.C., Susulic, V.S., Lowell, B.B., Maratos-Flier, E., and Flier, J.S. (1996). Activation of beta3 adrenergic receptors suppresses leptin expression and mediates a leptin-independent inhibition of food intake in mice. Diabetes 45, 909-914.
65. Marks, J.L., Li, M., Schwartz, M., Porte, D, Jr., and Baskin, D.G. (1992). Effect of fasting on regional levels of Neuropeptide Y mRNA and insulin receptors in the rat hypothalamus: an autoradiographic study. Mol. Cell. Neurosci. 3, 199-205.
66. Naggert, J.K., Fricker, L.D., Varlamov, O. Nishina, P.M., Rouille, Y., Steiner, D.F., Carroll, R.J., Paigen, B.J., and Leiter, E.H. (1995). Hyperproinsulinaemia in obese fat/fat mice associated with a carboxypeptidase E mutation which reduces enzyme activity. Nature Genet. 10, 134-142.
67. Noben-Trauth, K., Naggert, J., North, M., and Nishina, P. (1996). A candidate for the mouse mutation tubby. Nature 380, 534-538.
68. Nolan, J.J., Ludvik, B., Beerdsen, P., Joyce, M., and Olefsky, J. (1994). Improvement in glucose tolerance and insulin resistance in obese subjects treated with troglitazone. N. Engl. J. Med. 331, 1188-1193.
69. O'Rahilly, S., Gray, H., Humphreys, P.J., Krook, A., Polonsky, K.S., White, A., Gibson, S., Taylor, K., and Carr, C. (1995). Brief report: impaired processing of prohormones associated with abnormalities of glucose homeostasis and adrenal function. N. Engl. J. Med. 333, 1386-1390.
70. Pellymounter, M.A., Cullen, M.J., Baker, M.B., Hecht, R., Winters, D., Boone, T., and Collins, F. (1995). Effects of the obese gene product on body weight regulation in ob/ob mice. Science 269, 540-543.
71. Phillips, M.S., Liu, Q., Hammond, H.A., Dugan, V., Hey, P.J., Caskey, C. T., and Hess, J.F. (1996). Leptin receptor missense mutation in the fatty Zucker rat. Nature Genet. 13, 18-19.
72. Qu, D., Ludwig, D., Gammeltoft, S., Piper, M., Pellymounter, M., Cullen, M., Mathes, W., Przypek, J., Kanarek, R., and Maratos-Flier, E. (1996). A role for melanin-concentrating hormone in the central regulation of feeding behavior. Nature 380, 243-247.
73. Rance, T., and Baker, B. (1979). The teleost melanin concentrating hormone-a pituitary hormone of hypothalamic origin. Gen. Comp. Endocrinol. 37, 64-73.
74. Reed, P., Ding, Y., Zu, W., Gather, C., Green, E., and Price, R. (1996). Extreme obesity may be linked to markers flanking the human ob gene. Diabetes 45, 691-694.
75. Rovere, C., Viale, A., Nahon, J.L., and Kitabgi, P. (1996). Impaired processing of brain proneurotensin and promelanin-concentrating hormone in obese fat/fat mice. Endocrinol. 137, 2954-2958.
76. Samad, F., and Loskutoff, D.J. (1996). Tissue distribution and regulation of plasminogen activator inhibitor-1 in obese mice. Mol. Medicine, in press.
77. Scherer, P.E., Williams, S., Fogliano, M., Baldini, G., and Lodish, H.F. (1995). A novel serum protein similar to Clq, produced exclusively in adipocytes. J. Biol. Chem. 270, 26746-26749.
78. Schwartz, M.W., Figlewitz, D.P., Baskin, D.G., Woods, S.C., and Porte, D., Jr. (1994). Insulin and the central regulation of energy balance: update. Endocr. Rev. 2, 109-113.
79. Schwartz, M., Baskin, D., Bukowski, T., Kuijper, J., Foster, D., Lasser, G., Prunkard, D., and Porte, D. (1996). Specificity of leptin action on elevated blood glucose levels and hypothalamic neuropeptide Y gene expression in ob/ob mice. Diabetes. 45, 531-535.
80. Schwartz, M.W., Peskind, E., Raskind, M. Boyko, E.J., and Porte, D., Jr. (1996). Cerebrospinal fluid leptin levels: relationship to plasma levels and to adiposity in humans. Nature Med. 2, 589-593.
81. Sears, I.B., MacGinnitie, M.A., Kovacs, L.G., and Graves, R.A. (1996). Differentiation-dependent expression of the brown adipocyte uncoupling protein gene: regulation by peroxisome proliferator-activated receptor-gamma. Mol. Cell. Biol. 16, 3410-3419.
82. Slieker, L., Sloop, K., Surface, P., Kriaciunas, A., Laquier, F., Manetta, J., Buevallesey, J., and Stephens, T. (1996). Regulation of expression of OB mRNA proteins by glucocorticoids and cAMP. J. Biol. Chem. 271, 5301-5304.
83. Stanley, B.G., Kyrkouli, S.E., Lampert, S., and Leibowitz, S.F. (1986). Neuropeptide Y chronically injected into the hypothalamus: a powerful neurochemical inducer of hyperphagia and obesity. Peptides 7, 1189-1192.
84. Stephens, T.W., Basinski, M., Briston, P.K., Bue-Valleskey, J.M., Burgett, S.G., Craft, L. Hale, J. Hoffman, J., Hsiung, H, Kriausciunas, A., MaKellar, W., Roseck, P.R., Jr., Schoner, B., Smith, D., Tinsley, F. C., Zhang, X.Y., and Heiman, N. (1995). The Role of neuropeptide Y in the antiobesity action of the ofoese gene product. Nature 377, 530-532.
85. Streicher, R., Kotzka, J., Muller-Wieland, D., Siemeister, G., Munck, M., Avci, H., and Krone, W. (1996). SREBP-1 mediates activation of the low density lipoprotein receptor promoter by insulin and insulin-like growth factor-1. J. Biol. Chem. 271, 7128-7133.
86. Susulic, V.S., Frederich, R.C., Jr., Lawitts, J., Tozzo, S., Kahn, B.B., Harper, M.E., Himms-Hagen, J., Flier, J.S., and Lowell, B.B. (1995). Targeted disruption of the β-3 adrinergic receptor gene. J. Biol. Chem. 270, 29483-29492.
87. Svedberg, J., Bjorntorp, P., Lonnroth, P., and Smith, U. (1991). Prevention of inhibitory effect of free fatty acids on insulin binding and action in isolated rat hepatocytes by etomixir. Diabetes 40, 783-786.
88. Szalkowski, D., White-Carrington, S., Berger, J., and Zhang, B. (1995). Antidiabetic thiazolidnediones block the inhibitory effect of tumor necrosis factor-alpha on differentiation, insulin-stimulated glucose uptake, and gene expression in 3T3-L1 cells. Endocrinology 136, 1474-1481.
89. Tartaglia, L.A., Dembrski, M., Weng, X., Deng, N., Culpepper, J., Devos, R., Richards, G.J., Campfield, L.A., Clark, F.T., Deeds, J., Muir, C., Sanker, S., Moriarty, A., Moore, K.J., SMutko, J.S., Mays, G.G., Woolf, E. A., Monroe, C.A., and Tepper, R.I. (1995). Identification and expression cloning of a leptin receptor, OB-R. Cell 83, 1263-1271.
90. Teboul, L, Gaillard, D., Staccini, L., Inadera, H., Amri, E.Z., and Grimaldi, P.A. (1995). Thiazolidinediones and fatty acids convert myogenic cells into adipose-like cells. J. Biol. Chem. 270, 28183-28187.
91. Tontonoz, P., Kim, J.B., Graves, R.A., and Spiegelman, B.M. (1993). ADD1: A novel helix-loop-helix protein associated with adipocyte determination and differentiation. Mol. Cell. Biol. 13, 4753-4759.
92. Tontonoz, P., Hu, E., Graves, R.A., Budavari, A.I., and Spiegelman, B.M. (1994a). mPPARγ2: tissue-specific regulator of an adipocyte enhancer. Genes Dev. 8, 1224-1234.
93. Tontonoz, P., Hu, E., Devine, J., Beale, E.G., and Spiegelman, B.M. (1994b). PPARγ2 regulates adipose expression of the phosphoenolpyruvate carboxykinase gene. Mol. Cell. Biol. 15, 351-357.
94. Tontonoz, P., Hu, E., and Spiegelman, B.M. (1994c). Stimulation of adipogenesis in fibroblasts by PPARγ2, a lipid-activated transcription factor. Cell 79, 1147-1156.
95. Vidal-Puig, A., Jimenez-Linan, M., Lowell, B.B., Hamann, A., Hu, E., Spiegelman, B., Flier, J.S., and Moller, D.E. (1996). Regulation of PPARγ gene expression by nutrition and obesity in rodents. J. Clin. Invest. 97, 2553-2561.
96. Wang, X., Sato, R., Brown, M.S., Hua, X., and Goldstein, J.L (1994). SREBP-1, a membrane-bound transcription factor released by sterol-regulated proteolysis. Cell 77, 53-62.
97. Wang, N., Finegold, M.J., Bradley, A., Ou, C., Abdelsayed, S.V., Wilde, M. D., Taylor, L.R., Wilson, D.R., and Darlington, G.J. (1995). Impaired energy homeostasis in C/EBP-α knockout mice. Science 269, 1108-1112.
98. West, D., Goudey-Lefevre, J., York, B., and Truett, G. (1995). Dietary obesity linked to genetic loci on chromosomes 9 and 15 in a polygenie mouse model. J. Clin. Invest. 94, 1410-1416.
99. Widen, E., Lehto, M., Kanninen, T., Walston, J., and Shuldiner, A.R. (1995). Association of a polymorphism in the beta 3-adrenergic-receptor gene with features of the insulin resistance syndrome in Fnns. N. Engl. J. Med. 333, 348-351.
100. Willson, T.M., Cobb, J.E., Cowan, D.J., Wiethe, R.W., Correa, I.D., Prakash, S.R., Beck, K.D., Moore, L.B., Kliewer, S.A., and Lehmann, J.M. (1996). The structure-activity relationship between peroxisome proliferator-activated receptor gamma agonism and the antihyperglycemic activity of thiazolidinediones. J. Med. Chem. 39, 665-668.
101. Wu, Z., Xie, Y., Bucher, N.L. R., and Farmer, S.R. (1995). Conditional ectopic expression of C/EBP-β in NIH-3T3 cells induces PPARγ and stimulates adipogenesis. Genes Dev. 9, 2350-2356.
102. Wu, Z., Bucher, N.L. R., and Farmer, S.R. (1996). Induction of peroxisome proliferator-activated receptor γ during conversion of 3T3 fibroblasts intoadipocytes is mediated by C/EBPβ, C/EBPδ and glucocorticoids. Mol. Cell. Biol. 16, 4128-4136.
103. Yeh, W.-C., Cao, M., Classen, M., and McKnight, S.L. (1995). Cascade regulation of terminal adipocyte differentiation by three members of the C/EBP family of leucine zipper proteins. Genes Dev. 9, 168-181.
104. Yokoyama, C., Wang, X., Briggs, M.R., Admon, A., Wu, J., Hua, X., Goldstein, J.L., and Brown, M.S. (1993). SREBP-1, a basic-helix-loop-helix-leucine zipper protein that controls transcription of the low density lipoprotein receptor gene. Cell 75, 187-197.
105. Yu, K., Bayona, W., Kallen, C.B., Harding, H.P., Ravera, C.P., McMahon, G., Brown, M., and Lazar, M.A. (1995). Differential activation of peroxisome proliferator-activator receptors by eicosanoids. J. Biol. Chem. 270, 23975-23983.
106. Yubero, P., Manchado, C., Cassard-Doulcier, A., Mampel, T., Vinas, O., Iglesias, R., Giralt, M., and Villarroya, F. (1994). CCAAT/enhancer binding proteins alpha and beta are transcriptional activators of the brown fat uncoupling protein gene promoter. Biochem. Biophys. Res. Commun. 198, 653-659.
107. Zarjevski, N., Cusin, I., Vettor, F., and Rohner-Jeanrenaud, F. (1993) Chronic intracereberoventricular neuropeptide-Y administration to normal rats mimics hormonal and metabolic changes of obesity. Endocrinol. 133, 1753-1758.
108. Zhang, Y., Proenca, R., Maffei, M., Barone, M., Leopold, L., and Friedman, J. (1994). Positional cloning of the mouse obese gene and its human homologue. Nature 372, 425-432.
109. Zhang, E, Graziano, M.P., Doebber, T.W., Leibowitz, M.D., White-Carrington, S., Szalkowski, D.M., Hey, P.J., Wu, M., Cullinan, C. A., Bailey, P. Löllmann, Frederich, R., Flier, J.S., Strader, C.D., and Smith R. G. (1996). Down-regulation of the expression of the obese gene by an antidiabetic thiazolidinedione in Zucker diabetic fatty rats and db/db mice. J. Biol. Chem. 271, 9455-9459.
110. Zheng, Z., Otani, H., Brown, M.S., and Goldstein, J.L. (1995). Independent regulation of sterol regulatory element-binding proteins 1 and 2 in hamster liver. Proc. Natl. Acad. Sci. USA 92, 935-938.
111. Zhu, Y., Alvares, K., Huang, Q., Rao, M.S., and Reddy, J.K. (1993). Cloning of a new member of the peroxisome proliferator-activated receptor gene family from mouse liver. J. Biol. Chem. 268, 26817-26820.
112. Zhu, Y., Qi, C., Korenberg, J.R., Chen, X.N., Noya, D., Rao, M.S., and Reddy, J.K. (1995). Structural organization of mouse peroxisome proliferator-activated receptor gamma (mPPAR gamma) gene: alternative promoter use and different splicing yield two PPAR gamma isoforms. Proc. Natl. Acad. Sci. USA 92, 7921-7925.