1. Cuenot, L., [Les races pures et leur combinaisons chez les souris]. Arch Zool Exper Gener, 1905. 3: p. 123-132.

2. Ingalls, A.M., M.M. Dickie, and G.D. Snell, Obese, a new mutation in the house mouse. J Hered, 1950. 41: p. 317-318.

3. Hummel, K.P., M.M. Dickie, and D.L. Coleman, Diabetes, a new mutation in the mouse. Science, 1966. 153: p. 1127-1128.

4. Kennedy, G.C., The role of depot fat in the hypothalamic control of food intake in the rat. Proc R Soc Lond (Biol), 1953. 140: p. 579-592.

5. Hervey, G.R., A hypothetical mechanism for the regulation of food intake in relation to energy balance. Proc Nutr Soc, 1969. 28(2): p. 54A-55A.

6. Coleman, D.L., Diabetes-obesity syndromes in mice. Diabetes, 1982. 31(Suppl(1 Pt 2)): p. 1-6.

7. Coleman, D.L. and E.M. Eicher, Fat (fat) and Tubby (tub): two autosomal recessive mutations causing obesity syndromes in the mouse. J Hered, 1990. 81: p. 424-428.

8. Bultman, S.J., E.J. Michaud, and R.P. Woychik, Molecular characterization of the mouse agouti locus. Cell, 1992. 71: p. 1195-1204.

9. Miller, M.W., et al., Cloning of the mouse agouti gene predicts a secreted protein ubiquitously expressed in mice carrying the lethal yellow mutation. Genes Dev, 1993. 7(3): p. 454-67.

10. Zhang, Y., et al., Positional cloning of the mouse obese gene and its human homologue. Nature, 1994. 372: p. 425-432.

11. Kleyn, P.W., et al., Identification and characterization of the mouse obesity gene tubby: a member of a novel gene family. Cell, 1996. 85(2): p. 281-90.

12. Noben-Trauth, K., et al., A candidate gene for the mouse mutation tubby. Nature, 1996. 380: p. 534-538.

13. Chua, S.C., et al., Phenotypes of mouse diabetes and rat fatty due to mutations in the OB (Leptin) receptor. Science, 1996. 271: p. 994-996.

14. Tartaglia, L.A., et al., Identification and expression cloning of a leptin receptor, OB-R. Cell, 1995. 83: p. 1263-1271.

15. Naggert, J.K., et al., Hyperproinsulinaemia in obese fat/fat mice associated with a carboxypeptidase E mutation which reduces enzyme activity. Nat Genet, 1995. 10(2): p. 135-42.

16. Leibel, R.L., And finally, genes for human obesity. Nat Genet, 1997. 16(3): p. 218-20.

17. Zucker, L.M. and T.F. Zucker, Fatty, a new mutation in the rat. J Hered, 1961. 52: p. 275-278.

18. Bahary, N., et al., Molecular mapping of the mouse db mutation. Proc Natl Acad Sci U S A, 1990. 87(21): p. 8642-6.

19. Truett, G.E., et al., Rat obesity gene fatty (fa) maps to chromosome 5: evidence for homology with the mouse gene diabetes (db). Proc. Natl. Acad. Sci. U.S.A., 1991. 88(17): p. 7806-9.

20. Chua, S.C., et al., Phenotype of fatty due to Gln269Pro mutation in the leptin receptor (Lepr). Diabetes, 1996. 45: p. 1141-1143.

21. Iida, M., et al., Phenotype-linked amino acid alteration in leptin receptor cDNA from Zucker fatty (fa/fa) rat. Biocem Biophys Res Comm, 1996. 222: p. 19-26.

22. Phillips, M., et al., Leptin receptor missense mutation in the fatty Zucker rat. Nature Genet, 1996. 13: p. 18-19.

23. Koletsky, S., Obese spontaneously hypertensive rats--a model for study of atherosclerosis. Exp Mol Pathol, 1973. 19(1): p. 53-60.

24. Kawano, K., et al., Spontaneous long-term hyperglycemic rat with diabetic complications. Otsuka Long-Evans Tokushima Fatty (OLETF) strain. Diabetes, 1992. 41(11): p. 1422-8.

25. Takiguchi, S., et al., Disrupted cholecystokinin type-A receptor (CCKAR) gene in OLETF rats. Gene, 1997. 197(1-2): p. 169-75.

26. Berne, R.M. and M.N. Levy, eds. Physiology. 3rd ed. 1993, Mosby Year Book: Boston. 1071 pp.

27. Palmiter, R.D., et al., Dramatic growth of mice that develop from eggs microinjected with metallothionein-growth hormone fusion genes. Nature, 1982. 300(5893): p. 611-5.

28. Lin, F.L., K. Sperle, and N. Sternberg, Recombination in mouse L cells between DNA introduced into cells and homologous chromosomal sequences. Proc Natl Acad Sci U S A, 1985. 82(5): p. 1391-5.

29. Pham, C.T., et al., Long-range disruption of gene expression by a selectable marker cassette. Proc Natl Acad Sci U S A, 1996. 93(23): p. 13090-5.

30. Dockstader, C.L. and D. van der Kooy, Mouse strain differences in opiate reward learning are explained by differences in anxiety, not reward or learning. J Neurosci, 2001. 21(22): p. 9077-81.

31. Ludwig, D.S., et al., Melanin-concentrating hormone overexpression in transgenic mice leads to obesity and insulin resistance. J Clin Invest, 2001. 107: p. 379-386.

32. Wakayama, T. and R. Yanagimachi, Cloning of male mice from adult tail-tip cells. Nat Genet, 1999. 22(2): p. 127-8.

33. Naggert, J.K., et al., Genomic analysis of the C57BL/Ks mouse strain. Mamm Genome, 1995. 6(2): p. 131-3.

34. Ewart-Toland, A., et al., Effect of the genetic background on the reproduction of leptin- deficient obese mice. Endocrinology, 1999. 140(2): p. 732-8.

35. Moon, B.C. and J.M. Friedman, The molecular basis of the obese mutation in ob2J mice. Genomics, 1997. 42(1): p. 152-6.

36. Coleman, D.L., Effects of parabiosis of obese with diabetes and normal mice. Diabetologia, 1973. 9: p. 294-298.

37. Campfield, L., et al., Recombinant mouse OB Protein: Evidence for a peripheral signal linking adiposity and central neural networks. Science, 1995. 269: p. 546-549.

38. Halaas, J.L., et al., Weight-reducing effects of the plasma protein encoded by the obese gene. Science, 1995. 269: p. 543-546.

39. Pelleymounter, M.A., et al., Effects of the obese gene product on body weight regulation in ob/ob mice. Science, 1995. 269: p. 540-543.

40. Coleman, D.L., Increased metabolic efficiency in obese mutant mice. Int J Obes, 1985. 9 Suppl 2: p. 69-73.

41. Cox, J.E. and T.L. Powley, Development of obesity in diabetic mice pair-fed with lean siblings. J Comp Physiol Psychol, 1977. 91(2): p. 347-58.

42. Coleman, D.L., Obese and diabetes: two mutant genes causing diabetes-obesity syndromes in mice. Diabetologia, 1978. 14: p. 141-148.

43. Ahima, R., et al., Role of leptin in the neuroendocrine response to fasting. Nature, 1996. 382: p. 382.

44. Montague, C.T., et al., Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature, 1997. 387(6636): p. 903-8.

45. Farooqi, I.S., et al., Brief report: Effects of recombinant leptin therapy in a child with congenital leptin deficiency. N Engl J Med, 1999. 341(12): p. 879-884.

46. Farooqi, I.S., et al., Partial leptin deficiency and human adiposity. Nature, 2001. 414(6859): p. 34-5.

47. Chung, W.K., et al., Heterozygosity for Lep(ob) or Lep(rdb) affects body composition and leptin homeostasis in adult mice. Am J Physiol, 1998. 274(4 Pt 2): p. R985-90.

48. Leibel, R.L., M. Rosenbaum, and J. Hirsch, Changes in energy expenditure resulting from altered body weight. N Engl J Med, 1995. 332(10): p. 621-8.

49. Rosenbaum, M., et al., Low dose leptin administration reverses effects of sustained weight- reduction on energy expenditure and circulating concentrations of thyroid hormones. J Clin Endocrinol Metab, 2002. 87(5): p. 2391.

50. Leiter, E.H., et al., A new mutation (db3J) at the diabetes locus in strain 129/J mice. I. Physiological and histological characterization. Diabetologia, 1980. 19(1): p. 58-65.

51. Leiter, E.H., D.L. Coleman, and K.P. Hummel, The influence of genetic background on the expression of mutations at the diabetes locus in the mouse. III. Effect of H-2 haplotype and sex. Diabetes, 1981. 30(12): p. 1029-34.

52. Chua, S., Jr., et al., Differential beta cell responses to hyperglycaemia and insulin resistance in two novel congenic strains of diabetes (FVB- Lepr (db)) and obese (DBA- Lep (ob)) mice. Diabetologia, 2002. 45(7): p. 976-90.

53. Coleman, D.L., Obesity genes: beneficial effects in heterozygous mice. Science, 1979. 203(4381): p. 663-5.

54. Boden, G., et al., Effect of fasting on serum leptin in normal human subjects. JCE & M, 1996. 81(9): p. 3419-3423.

55. Lee, G., et al., Abnormal splicing of the leptin receptor in diabetic mice. Nature, 1996. 379: p. 632-635.

56. Bates, S.H., et al., STAT3 signalling is required for leptin regulation of energy balance but not reproduction. Nature, 2003. 421(6925): p. 856-9.

57. Hileman, S.M., et al., Characterizaton of short isoforms of the leptin receptor in rat cerebral microvessels and of brain uptake of leptin in mouse models of obesity. Endocrinology, 2002. 143(3): p. 775-83.

58. Sinha, M.K., et al., Evidence of free and bound leptin in human circulation. Studies in lean and obese subjects and during short-term fasting. J Clin Invest, 1996. 98(6): p. 1277-82.

59. Wang, M.Y., et al., A novel leptin receptor isoform in rat. FEBS Lett, 1996. 392(2): p. 87-90.

60. Fei, H., et al., Anatomic localization of alternatively spliced leptin receptors (Ob-R) in mouse brain and other tissues. Proc Natl Acad Sci U S A, 1997. 94(13): p. 7001-5.

61. Cheung, C., D. Clifton, and R. Steiner, Proopimelanocortin neurons are direct targets for leptin in the hypothalamus. Endocrinology, 1997. 138(10): p. 4489-4492.

62. Baskin, D.G., J.F. Breininger, and M.W. Schwartz, Leptin receptor mRNA identifies a subpopulation of neuropeptide Y neurons activated by fasting in rat hypothalamus. Diabetes, 1999. 48(4): p. 828-33.

63. Kaufmann, R.C., et al., An animal model of gestational diabetes. Am J Obstet Gynecol, 1981. 141(5): p. 479-82.

64. Yamashita, H., et al., Leptin administration prevents spontaneous gestational diabetes in heterozygous Lepr(db/+) mice: effects on placental leptin and fetal growth. Endocrinology, 2001. 142(7): p. 2888-97.

65. Leiter, E.H., I. Strack, and A.B. Eisenstein, A new mutation (db3J) at the diabetes locus in strain 129/J mice. II. Studies of pancreatic alpha cell function in culture. Diabetologia, 1980. 19(1): p. 66-73.

66. Guenet, J.L., A mutation in the DW inbred line producing an obese phenotype. Mouse News Lett, 1982. 67: p. 30.

67. Brown, J.A., et al., Spontaneous mutation in the db gene results in obesity and diabetes in CD-1 outbred mice. Am J Physiol Regul Integr Comp Physiol, 2000. 278(2): p. R320-30.

68. Lane, P.W., [New allele of diabetes]. Mouse News Lett, 1968. 38: p. 24.

69. Falconer, D.S. and J.H. Isaacson, Adipose, a new inherited obesity of the mouse. J Hered, 1959. 50: p. 290-292.

70. Lee, G., et al., Leptin receptor mutations in 129 db3J/db3J mice and NIH facp/facp rats. Mamm Genome, 1997. 8(6): p. 445-7.

71. White, D.W., et al., Constitutive and impaired signaling of leptin receptors containing the Gln --> Pro extracellular domain fatty mutation. Proc Natl Acad Sci U S A, 1997. 94(20): p. 10657-62.

72. Takaya, K., et al., Nonsense mutation of leptin receptor in the obese spontaneously hypertensive Koletsky rat. Nat Genet, 1996. 14(2): p. 130-1.

73. Wu-Peng, W., et al., Phenotype of the obese Koletsky (f) rat due to Tyr763Stop mutation in the extracellular domain of the leptin receptor (Lepr): evidence for deficient plasma-to-CSF transport of leptin in both the Zucker and Loletsky obese rat. Diabetes, 1997. 46(3): p. 513-518.

74. Kowalski, T.J., et al., Transgenic complementation of leptin-receptor deficiency. I. Rescue of the obesity/diabetes phenotype of LEPR-null mice expressing a LEPR-B transgene. Diabetes, 2001. 50(2): p. 425-35.

75. Cohen, P., et al., Selective deletion of leptin receptor in neurons leads to obesity. J Clin Invest, 2001. 108(8): p. 1113-21.

76. Dickie, M.M., A new viable yellow mutation in the house mouse. J Hered, 1962. 53: p. 84-86.

77. Cowley, M.A., et al., Integration of NPY, AGRP, and melanocortin signals in the hypothalamic paraventricular nucleus: evidence of a cellular basis for the adipostat. Neuron, 1999. 24(1): p. 155-63.

78. Lu, D., et al., Agouti protein is an antagonist of the melanocyte-stimulating-hormone receptor. Nature, 1994. 371(6500): p. 799-802.

79. Dinulescu, D.M., et al., Mahogany (mg) stimulates feeding and increases basal metabolic rate independent of its suppression of agouti. Proc Natl Acad Sci U S A, 1998. 95: p. 12707-12712.

80. Mendel, V.E., Influence of the insulin-to-growth hormone ratio on body composition of mice. Am J Physiol, 1980. 238(3): p. E231-4.

81. Trayhurn, P., Thermoregulation in the diabetic-obese (db/db) mouse. The role of non- shivering thermogenesis in energy balance. Pflugers Arch, 1979. 380(3): p. 227-32.

82. Kaplan, M.L. and G.A. Leveille, Core temperature, O2 consumption, and early detection of ob-ob genotype in mice. Am J Physiol, 1974. 227(4): p. 912-5.

83. Zemel, M.B., Agouti/melanocortin interactions with leptin pathways in obesity. Nutr Rev, 1998. 56(9): p. 271-4.

84. Stubdal, H., et al., Targeted deletion of the tub mouse obesity gene reveals that tubby is a loss-of-function mutation. Mol Cell Biol, 2000. 20(3): p. 878-882.

85. Santagata, S., et al., G-protein signaling through tubby proteins. Science, 2001. 292(5524): p. 2041-50.

86. Fricker, L.D., Peptide Biosynthesis and Processing, L.D. Fricker, Editor. 1991, CRC Press, Inc.: Boca Raton, FL. p. 199-230.

87. Berman, Y., et al., Impaired prohormone convertases in Cpefat/Cpefat mice. J Biol Chem, 2001. 276(2): p. 1466-1473.

88. Leiter, E.H., Obesity and the adipocyte: carboxypeptidase E and obesity in the mouse. J Endocrinol, 1997. 155: p. 211-214.

89. Chen, H., et al., Missense polymorphism in the human carboxypeptidase E gene alters enzymatic activity. Hum Mutat, 2001. 18(2): p. 120-31.

90. Jackson, R.S., et al., Obesity and impaired prohormone processing associated with mutations in the human prohormone convertase 1 gene. Nat Genet, 1997. 16(3): p. 303-6.

91. Lane, P.W. and M.C. Green, Mahogany, a recessive color mutation in linkage group V of the mouse. J Hered, 1960. 51: p. 228-230.

92. Lane, P.W., Mahoganoid, md. Mouse News Lett, 1960. 22: p. 35.

93. Gunn, T.M., et al., The mouse mahogany locus encodes a transmembrane form of human attractin. Nature, 1999. 398: p. 152-156.

94. Duke-Cohan, J.S., et al., Attractin (DPPT-L), a member of the CUB family of cell adhesion and guidance proteins, is secreted by activated human T lymphocytes and modulates immune cell interactions. Proc Natl Acad Sci U S A, 1998. 95(19): p. 11336-41.

95. Miller, K.A., et al., Genetic studies of the mouse mutations mahogany and mahoganoid. Genetics, 1997. 146(4): p. 1407-15.

96. Nagle, D., et al., The mahogany protein is a receptor involved in suppression of obesity. Nature, 1999. 398: p. 148-152.

97. Kuramoto, T., et al., Attractin/mahogany/zitter plays a critical role in myelination of the central nervous system. Proc Natl Acad Sci U S A, 2001. 98(2): p. 559-64.

98. Rehm, S., et al., A new rat mutant with defective overhairs and spongy degeneration of the central nervous system: clinical and pathologic studies. Lab Anim Sci, 1982. 32(1): p. 70-3.

99. Yamada, T., et al., Assignment of tremulous body mutant gene zitter (zi) to linkage group IV of the rat (Rattus norvegicus). J Hered, 1989. 80(5): p. 383-6.

100. Phan, L.K., et al., The mouse mahoganoid coat color mutation disrupts a novel C3HC4 RING domain protein. J Clin Invest, 2002. 110(10): p. 1449-59.

101. He, L., et al., Spongiform degeneration in mahoganoid mutant mice. Science, 2003. 299(5607): p. 710-2.

102. Chagnon, Y.C., et al., The Human Obesity Gene Map: The 2002 Update. Obes Res, 2003. 11(3): p. 313-367.

103. Kanemoto, N., et al., Genetic dissection of "OLETF", a rat model for non-insulin-dependent diabetes mellitus. Mamm Genome, 1998. 9(6): p. 419-25.

104. Watanabe, T.K., et al., Genetic dissection of "OLETF," a rat model for non-insulin-dependent diabetes mellitus: quantitative trait locus analysis of (OLETF x BN) x OLETF. Genomics, 1999. 58(3): p. 233-9.

105. Ogino, T., et al., Genetic evidence for obesity loci involved in the regulation of body fat distribution in obese type 2 diabetes rat, OLETF. Genomics, 2000. 70(1): p. 19-25.

106. Ikeda, H., et al., A new genetically obese-hyperglycemic rat (Wistar fatty). Diabetes, 1981. 30(12): p. 1045-50.

107. Chung, W.K., et al., Genetic modifiers of Leprfa associated with variability in insulin production and susceptibility to NIDDM. Genomics, 1997. 41(3): p. 332-44.

108. Heitmann, B.L. and L. Garby, Patterns of long-term weight changes in overweight developing Danish men and women aged between 30 and 60 years. Int J Obes Relat Metab Disord, 1999. 23(10): p. 1074-8.

109. Kuczmarski, R.J., Prevalence of overweight and weight gain in the United States. Am J Clin Nutr, 1992. 55(2 Suppl): p. 495S-502S.

110. Solomon, C.G. and J.E. Manson, Obesity and mortality: a review of the epidemiologic data. Am J Clin Nutr, 1997. 66(4 Suppl): p. 1044S-1050S.

111. West, D.B., et al., Dietary obesity in nine inbred mouse strains. Am J Physiol, 1992. 262(6 Pt 2): p. R1025-32.

112. West, D.B., et al., Genetics of dietary obesity in AKR/J x SWR/J mice: segregation of the trait and identification of a linked locus on chromosome 4. Mamm Genome, 1994. 5(9): p. 546-52.

113. West, D.B., et al., Dietary obesity linked to genetic loci on chromosomes 9 and 15 in a polygenic mouse model. J Clin Invest, 1994. 94(4): p. 1410-6.

114. Walder, K., et al., Ob (obese) gene expression and leptin levels in Psammomys obesus. Biochim Biophys Acta, 1997. 1354(3): p. 272-8.

115. Nesher, R., et al., Interaction between genetic and dietary factors determines beta-cell function in Psammomys obesus, an animal model of type 2 diabetes. Diabetes, 1999. 48(4): p. 731-7.

116. Donath, M.Y., et al., Hyperglycemia-induced beta-cell apoptosis in pancreatic islets of Psammomys obesus during development of diabetes. Diabetes, 1999. 48(4): p. 738-44.

117. van den Brandt, J., P. Kovacs, and I. Kloting, Features of the metabolic syndrome in the spontaneously hypertriglyceridemic Wistar Ottawa Karlsburg W (RT1u Haplotype) rat. Metabolism, 2000. 49(9): p. 1140-4.

118. Kovacs, P., et al., WOK.1W rats. A potential animal model of the insulin resistance syndrome. Ann N Y Acad Sci, 1997. 827: p. 94-9.

119. Kloting, I., P. Kovacs, and J. van den Brandt, Sex-specific and sex-independent quantitative trait loci for facets of the metabolic syndrome in WOKW rats. Biochem Biophys Res Commun, 2001. 284(1): p. 150-6.

120. Galli, J., et al., Genetic analysis of non-insulin dependent diabetes mellitus in the GK rat. Nat Genet, 1996. 12(1): p. 31-7.

121. Gauguier, D., et al., Chromosomal mapping of genetic loci associated with non-insulin dependent diabetes in the GK rat. Nat Genet, 1996. 12(1): p. 38-43.

122. Duggirala, R., et al., Linkage of type 2 diabetes mellitus and of age at onset to a genetic location on chromosome 10q in Mexican Americans. Am J Hum Genet, 1999. 64(4): p. 1127-40.

123. Crofford, O.B. and C.K. Davis, Growth characteristics, glucose tolerance and insulin sensitivity of New Zealand Obese mice. Metabolism, 1965. 14: p. 271-280.

124. Kluge, R., et al., Quantitative trait loci for obesity and insulin resistance (Nob1, Nob2) and their interaction with the leptin receptor allele (LeprA720T/T1044I) in New Zealand obese mice. Diabetologia, 2000. 43(12): p. 1565-72.

125. Igel, M., et al., Hyperleptinemia, leptin resistance, and polymorphic leptin receptor in the New Zealand obese mouse. Endo, 1997. 138(10): p. 4234-4239.

126. Taylor, B.A., et al., Multiple obesity QTLs identified in an intercross between the NZO (New Zealand obese) and the SM (small) mouse strains. Mamm Genome, 2001. 12(2): p. 95-103.

127. Reifsnyder, P.C., G. Churchill, and E.H. Leiter, Maternal environment and genotype interact to establish diabesity in mice. Genome Res, 2000. 10(10): p. 1568-78.

128. Suzuki, W., et al., A new mouse model of spontaneous diabetes derived from ddY strain. Exp Anim, 1999. 48(3): p. 181-9.

129. Hirayama, I., et al., Genetic analysis of obese diabetes in the TSOD mouse. Diabetes, 1999. 48(5): p. 1183-91.

130. Erickson, J.C., K.E. Clegg, and R.D. Palmiter, Sensitivity to leptin and susceptibility to seizures of mice lacking neuropeptide Y. Nature, 1996. 381(6581): p. 415-21.

131. Marsh, D.J., et al., Effects of neuropeptide Y deficiency on hypothalamic agouti-related protein expression and responsiveness to melanocortin analogues. Brain Res, 1999. 848(1-2): p. 66-77.

132. Qian, S., et al., Neither agouti-related protein nor neuropeptide Y is critically required for the regulation of energy homeostasis in mice. Mol Cell Biol, 2002. 22(14): p. 5027-35.

133. Erickson, J.C., G. Hollopeter, and R.D. Palmiter, Attenuation of the obesity syndrome of ob/ob mice by the loss of neuropeptide Y. Science, 1996. 274: p. 1704-1707.

134. Bannon, A.W., et al., Behavioral characterization of neuropeptide Y knockout mice. Brain Res, 2000. 868(1): p. 79-87.

135. Shimizu-Albergine, M., D.L. Ippolito, and J.A. Beavo, Downregulation of fasting-induced cAMP response element-mediated gene induction by leptin in neuropeptide Y neurons of the arcuate nucleus. J Neurosci, 2001. 21(4): p. 1238-46.

136. Weinberg, D.H., et al., Cloning and expression of a novel neuropeptide Y receptor. J Biol Chem, 1996. 271(28): p. 16435-16438.

137. Burkhoff, A., D.L. Linemeyer, and J.A. Salon, Distribution of a novel hypothalamic neuropeptide Y receptor gene and it's absence in rat. Brain Res Mol Brain Res, 1998. 53(1-2): p. 311-6.

138. Jenkinson, C.P., et al., Novel polymorphisms in the neuropeptide-Y Y5 receptor associated with obesity in Pima Indians. Int J Obes Relat Metab Disord, 2000. 24(5): p. 580-4.

139. Pedrazzini, T., et al., Cardiovascular response, feeding behavior and locomotor activity in mice lacking the NPY Y1 receptor. Nat Med, 1998. 4(6): p. 722-26.

140. Marsh, D.J., et al., Role of the Y5 neuropeptide Y receptor in feeding and obesity. Nat Med, 1998. 4(6): p. 718-21.

141. Sainsbury, A., et al., Important role of hypothalamic Y2 receptors in body weight regulation revealed in conditional knockout mice. Proc Natl Acad Sci U S A, 2002. 99(13): p. 8938-43.

142. Batterham, R.L., et al., Gut hormone PYY(3-36) physiologically inhibits food intake. Nature, 2002. 418(6898): p. 650-4.

143. Kawauchi, H., et al., Characterization of melanin-concentrating homone in chum salmon pituitaries. Nature, 1983. 305: p. 321.

144. Nahon, J.L., The melanin-concentrating hormone: from the peptide to the gene. Crit Rev Neurobiol, 1994. 8(4): p. 221-62.

145. Qu, D., et al., A role for melanin-concentrating hormone in the central regulation of feeding behaviour. Nature, 1996. 380: p. 243-247.

146. Anand, B.K. and J.R. Brobeck, Hypothalamic control of food intake in rats and cats. Yale J Biol Med, 1951. 24: p. 123-140.

147. Mondal, M.S., M. Nakazato, and S. Matsukura, Characterization of orexins (hypocretins) and melanin-concentrating hormone in genetically obese mice. Reg Peptides, 2002. 104: p. 21-25.

148. Shimada, M., et al., Mice lacking melanin-concentrating hormone are hypophagic and lean. Nature, 1998. 396: p. 670-673.

149. Surwit, R.S., et al., Diet-induced type II diabetes in C57BL/6J mice. Diabetes, 1988. 37(9): p. 1163-7.

150. Saito, Y., H.-P. Nothacker, and O. Civelli, Trends Endocrinol Metab, 2000. 11: p. 299-303.

151. Marsh, D.J., et al., Melanin-concentrating hormone 1 receptor-deficient mice are lean, hyperactive, and hyperphagic and have altered metabolism. Proc Natl Acad Sci U S A, 2002. 99(5): p. 3240-5.

152. Shor-Posner, G., et al., Hypothalamic serotonin in the control of meal patterns and macronutrient selection. Brain Res Bull, 1986. 17(5): p. 663-71.

153. Weintraub, M., et al., Sibutramine in weight control: a dose-ranging, efficacy study. Clin Pharmacol Ther, 1991. 50(3): p. 330-7.

154. Tecott, L.H., et al., Eating disorder and epilepsy in mice lacking 5-HT2c serotonin receptors. Nature, 1995. 374(6522): p. 542-6.

155. Nonogaki, K., et al., Leptin-independent hyperphagia and type 2 diabetes in mice with a mutated serotonin 5-HT2C receptor gene. Nat Med, 1998. 4(10): p. 1152-6.

156. Alvaro, J.D., et al., Morphine down-regulates melanocortin-4 receptor expression in brain regions that mediate opiate addiction. Mol Pharmacol, 1996. 50(3): p. 583-91.

157. Adan, R.A., et al., Differential effects of melanocortin peptides on neural melanocortin receptors. Mol Pharmacol, 1994. 46(6): p. 1182-90.

158. Gantz, I., et al., Molecular cloning, expression, and gene localization of a fourth melanocortin receptor. J Biol Chem, 1993. 268(20): p. 15174-9.

159. Miwa, H., et al., Structural determinants of the melanocortin peptides required for activation of melanocortin-3 and melanocortin-4 receptors. J Pharmacol Exp Ther, 1995. 273(1): p. 367-72.

160. Mountjoy, K.G., et al., Localization of the melanocortin-4 receptor (MC4-R) in neuroendocrine and autonomic control circuits in the brain. Mol Endocrinol, 1994. 8(10): p. 1298-308.

161. Cone, R., et al., The melanocortin receptors: agonists, antagonists, and the hormonal control of pigmentation. Recent Progress In Hormone Research, 1996. 51: p. 287-318.

162. Nijenhuis, W.A., J. Oosterom, and R.A. Adan, AgRP(83-132) acts as an inverse agonist on the human-melanocortin-4 receptor. Mol Endocrinol, 2001. 15(1): p. 164-71.

163. Haskell-Luevano, C. and E.K. Monck, Agouti-related protein functions as an inverse agonist at a constitutively active brain melanocortin-4 receptor. Regul Pept, 2001. 99(1): p. 1-7.

164. Ollmann, M., et al., Antagonism of central melanocortin receptors in vitro and in vivo by agouti-related protein. Science, 1997. 278: p. 135-138.

165. Huszar, D., et al., Targeted disruption of the melanocortin-4 receptor results in obesity in mice. Cell, 1997. 88: p. 131-141.

166. Ste Marie, L., et al., A metabolic defect promotes obesity in mice lacking melanocortin-4 receptors. Proc Natl Acad Sci U S A, 2000. 97(22): p. 12339-44.

167. Chen, A.S., et al., Role of the melanocortin-4 receptor in metabolic rate and food intake in mice. Transgenic Res, 2000. 9(2): p. 145-54.

168. Farooqi, I.S., et al., Clinical spectrum of obesity and mutations in the melanocortin 4 receptor gene. N Engl J Med, 2003. 348(12): p. 1085-95.

169. Vaisse, C., et al., Melanocortin-4 receptor mutations are a frequent and heterogenous cause of morbid obesity. J Clin Invest, 2000. 106(2): p. 253-262.

170. Farooqi, I.S., et al., Dominant and recessive inheritance of morbid obesity associated with melanocortin 4 receptor deficiency. J Clin Invest, 2000. 106(2): p. 271-9.

171. Kobayashi, H., et al., A Novel homozygous missense mutation of melanocortin-4 receptor (MC4R) in a Japanese woman with severe obesity. Diabetes, 2002. 51(1): p. 243-6.

172. Schioth, H.B., et al., The melanocortin 1, 3, 4 or 5 receptors do not have a binding epitope for ACTH beyond the sequence of alpha-MSH. J Endocrinol, 1997. 155(1): p. 73-8.

173. Chen, A.S., et al., Inactivation of the mouse melanocortin-3 receptor results in increased fat mass and reduced lean body mass. Nat Genet, 2000. 26(1): p. 97-102.

174. Butler, A.A., et al., A unique metabolic syndrome causes obesity in the melanocortin-3 receptor-deficient mouse. Endocrinology, 2000. 141(9): p. 3518-21.

175. Lee, Y.S., L.K. Poh, and K.Y. Loke, A novel melanocortin 3 receptor gene (MC3R) mutation associated with severe obesity. J Clin Endocrinol Metab, 2002. 87(3): p. 1423-6.

176. Schalin-Jantti, C., et al., Melanocortin-3-receptor gene variants in morbid obesity. Int J Obes Relat Metab Disord, 2003. 27(1): p. 70-4.

177. Krude, H., et al., Severe early-onset obesity, adrenal insufficiency and red hair pigmentation caused by POMC mutations in humans. Nat Genet, 1998. 19: p. 155-57.

178. Yaswen, L., et al., Obesity in the mouse model of pro-opiomelanocortin deficiency responds to peripheral melanocortin. Nat Med, 1999. 5(9): p. 1066-70.

179. Smart, J.L. and M.J. Low. Transgenic rescue of pituitary POMC in the null background reverses adrenal insufficiency and augments obesity of POMC-deficient mice. in The Endocrine Society's 84th Annual Meeting. 2002. San Francisco, CA.

180. Seidah, N.G. and M. Chretien, Proprotein and prohormone convertases: a family of subtilases generating diverse bioactive polypeptides. Brain Res, 1999. 848(1-2): p. 45-62.

181. O'Rahilly, S., et al., Brief report: impaired processing of prohormones associated with abnormalities of glucose homeostasis and adrenal function. N Engl J Med, 1995. 333(21): p. 1386-90.

182. Shutter, J.R., et al., Hypothalamic expression of ART, a novel gene related to agouti, is upregulated in obese and diabetic mutant mice. Genes Dev, 1997. 11: p. 593-602.

183. Hagan, M.M., et al., Long-term orexigenic effects of AgRP-(83---132) involve mechanisms other than melanocortin receptor blockade [In Process Citation]. Am J Physiol Regul Integr Comp Physiol, 2000. 279(1): p. R47-52.

184. Reizes, O., et al., Transgenic expression of syndecan-1 uncovers a physiological control of feeding behavior by syndecan-3. Cell, 2001. 106(1): p. 105-16.

185. Unger, J., et al., Distribution of insulin receptor-like immunoreactivity in the rat forebrain. Neuroscience, 1989. 31: p. 143-157.

186. Sipols, A.J., D.G. Baskin, and M.W. Schwartz, Effect of intracerebroventricular insulin infusion on diabetic hyperphagia and hypothalamic neuropeptide gene expression. Diabetes, 1995. 44(2): p. 147-51.

187. Benoit, S.C., et al., The catabolic action of insulin in the brain is mediated by melanocortins. J Neurosci, 2002. 22(20): p. 9048-52.

188. Bruning, J.C., et al., Role of brain insulin receptor in control of body weight and reproduction. Science, 2000. 289(5487): p. 2122-5.

189. Burks, D.J., et al., IRS-2 pathways integrate female reproduction and energy homeostasis. Nature, 2000. 407(6802): p. 377-82.

190. Kulkarni, R.N., et al., Tissue-specific knockout of the insulin receptor in pancreatic beta cells creates an insulin secretory defect similar to that in type 2 diabetes. Cell, 1999. 96(3): p. 329-39.

191. Bruning, J.C., et al., A muscle-specific insulin receptor knockout exhibits features of the metabolic syndrome of NIDDM without altering glucose tolerance. Mol Cell, 1998. 2(5): p. 559-69.

192. Kim, J.K., et al., Redistribution of substrates to adipose tissue promotes obesity in mice with selective insulin resistance in muscle. J Clin Invest, 2000. 105(12): p. 1791-7.

193. Yuan, M., et al., Reversal of obesity- and diet-induced insulin resistance with salicylates or targeted disruption of Ikkbeta. Science, 2001. 293(5535): p. 1673-7.

194. Elchebly, M., et al., Increased insulin sensitivity and obesity resistance in mice lacking the protein tyrosine phosphatase-1B gene. Science, 1999. 283(5407): p. 1544-8.

195. Klaman, L.D., et al., Increased energy expenditure, decreased adiposity, and tissue-specific insulin sensitivity in protein-tyrosine phosphatase 1B-deficient mice. Mol Cell Biol, 2000. 20(15): p. 5479-89.

196. Cheng, A., et al., Attenuation of leptin action and regulation of obesity by protein tyrosine phosphatase 1B. Dev Cell, 2002. 2(4): p. 497-503.

197. Pacak, K. and M. Palkovits, Stressor specificity of central neuroendocrine responses: implications for stress-related disorders. Endocr Rev, 2001. 22(4): p. 502-48.

198. Morley, J.E. and A.S. Levine, Corticotrophin releasing factor, grooming and ingestive behavior. Life Sci, 1982. 31(14): p. 1459-64.

199. Stenzel-Poore, M.P., et al., Development of Cushing's syndrome in corticotropin-releasing factor transgenic mice. Endocrinology, 1992. 130(6): p. 3378-86.

200. Muglia, L., et al., Corticotropin-releasing hormone deficiency reveals major fetal but not adult glucocorticoid need. Nature, 1995. 373(6513): p. 427-32.

201. Grigoriadis, D.E., et al., Characterization of corticotropin-releasing factor receptor subtypes. Ann N Y Acad Sci, 1996. 780: p. 60-80.

202. Bale, T.L., et al., Mice deficient for both corticotropin-releasing factor receptor 1 (CRFR1) and CRFR2 have an impaired stress response and display sexually dichotomous anxiety-like behavior. J Neurosci, 2002. 22(1): p. 193-9.

203. Chalmers, D.T., T.W. Lovenberg, and E.B. De Souza, Localization of novel corticotropin-releasing factor receptor (CRF2) mRNA expression to specific subcortical nuclei in rat brain: comparison with CRF1 receptor mRNA expression. J Neurosci, 1995. 15(10): p. 6340-50.

204. Heinrichs, S.C., et al., Corticotropin-releasing factor CRF1, but not CRF2, receptors mediate anxiogenic-like behavior. Regul Pept, 1997. 71(1): p. 15-21.

205. Smagin, G.N., et al., The role of CRF2 receptors in corticotropin-releasing factor- and urocortin-induced anorexia. Neuroreport, 1998. 9(7): p. 1601-6.

206. Timpl, P., et al., Impaired stress response and reduced anxiety in mice lacking a functional corticotropin-releasing hormone receptor 1. Nat Genet, 1998. 19(2): p. 162-6.

207. Kishimoto, T., et al., Deletion of crhr2 reveals an anxiolytic role for corticotropin- releasing hormone receptor-2. Nat Genet, 2000. 24(4): p. 415-9.

208. Lewis, K., et al., Identification of urocortin III, an additional member of the corticotropin-releasing factor (CRF) family with high affinity for the CRF2 receptor. Proc Natl Acad Sci U S A, 2001. 98(13): p. 7570-5.

209. Spina, M., et al., Appetite-suppressing effects of urocortin, a CRF-related neuropeptide. Science, 1996. 273(5281): p. 1561-1563.

210. Karolyi, I.J., et al., Altered anxiety and weight gain in corticotropin-releasing hormone- binding protein-deficient mice. Proc Natl Acad Sci U S A, 1999. 96(20): p. 11595-600.

211. Lovejoy, D.A., et al., Ectopic expression of the CRF-binding protein: minor impact on HPA axis regulation but induction of sexually dimorphic weight gain. J Neuroendocrinol, 1998. 10(7): p. 483-91.

212. Kirk, L.F., Jr., et al., Cushing's disease: clinical manifestations and diagnostic evaluation. Am Fam Physician, 2000. 62(5): p. 1119-27, 1133-4.

213. Tronche, F., et al., Disruption of the glucocorticoid receptor gene in the nervous system results in reduced anxiety. Nat Genet, 1999. 23(1): p. 99-103.

214. Kellendonk, C., et al., Inactivation of the GR in the Nervous System Affects Energy Accumulation. Endocrinology, 2002. 143(6): p. 2333-40.

215. Morley, J.E. and A.S. Levine, Corticotrophin releasing factor, grooming and ingestive behavior. Life Sci, 1982. 31(14): p. 1459-64.

216. Rask, E., et al., Tissue-specific dysregulation of cortisol metabolism in human obesity. J Clin Endocrinol Metab, 2001. 86(3): p. 1418-21.

217. Bjorntorp, P. and R. Rosmond, Obesity and cortisol. Nutrition, 2000. 16(10): p. 924-36.

218. Hauner, H., P. Schmid, and E.F. Pfeiffer, Glucocorticoids and insulin promote the differentiation of human adipocyte precursor cells into fat cells. J Clin Endocrinol Metab, 1987. 64(4): p. 832-5.

219. Masuzaki, H., et al., A transgenic model of visceral obesity and the metabolic syndrome. Science, 2001. 294(5549): p. 2166-70.

220. Finck, B.N. and R.W. Johnson, Anorexia, weight loss and increased plasma interleukin-6 caused by chronic intracerebroventricular infusion of interleukin-1beta in the rat. Brain Res, 1997. 761(2): p. 333-7.

221. Yao, J.H., et al., Mice deficient in interleukin-1beta converting enzyme resist anorexia induced by central lipopolysaccharide. Am J Physiol, 1999. 277(5 Pt 2): p. R1435-43.

222. Hirsch, E., et al., Functions of interleukin 1 receptor antagonist in gene knockout and overproducing mice. Proc Natl Acad Sci U S A, 1996. 93(20): p. 11008-13.

223. Wallenius, V., et al., Interleukin-6-deficient mice develop mature-onset obesity. Nat Med, 2002. 8(1): p. 75-9.

224. Fraser, R., et al., Cortisol effects on body mass, blood pressure, and cholesterol in the general population. Hypertension, 1999. 33(6): p. 1364-8.

225. Trayhurn, P. and J.H. Beattie, Physiological role of adipose tissue: white adipose tissue as an endocrine and secretory organ. Proc Nutr Soc, 2001. 60(3): p. 329-39.

226. Bray, G.A., Autonomic and endocrine factors in the regulation of food intake. Int J Obes, 1989. 13(3): p. 327-335.

227. Holder, J.L.J., N.F. Butte, and A.R. Zinn, Profound obesity associated with a balanced translocation that disrupts the SIM1 gene. Hum Mol Genet, 2000. 9: p. 101-108.

228. Villa, A., et al., De novo interstitial deletion q16.2q21 on chromosome 6. Am J Med Genet, 1995. 55: p. 379-383.

229. Turleau, C., et al., 6q1 monosomy: a distinctive syndrome. Clin Genet, 1988. 34: p. 38-42.

230. Michaud, J.L., et al., Sim1 haploinsufficiency causes hyperphagia, obesity and reduction of the paraventricular nucleus of the hypothalamus. Hum Mol Genet, 2001. 10(14): p. 1465-73.

231. Hetherington, A.W. and S.W. Ranson, Hypothalamic lesions and obesity in the rat. Anat Rec, 1940. 78: p. 149-172.

232. Ingraham, H.A., et al., The nuclear receptor steroidogenic factor 1 acts at multiple levels of the reproductive axis. Genes Dev, 1994. 8(19): p. 2302-12.

233. Luo, X., Y. Ikeda, and K.L. Parker, A cell-specific nuclear receptor is essential for adrenal and gonadal development and sexual differentiation. Cell, 1994. 77(4): p. 481-90.

234. Majdic, G., et al., Konckout mice lacking steroidogenic factor 1 are a novel genetic model of hypothalamic obesity. Endocrinol, 2002. 143(2): p. 607-614.

235. Niikawa, N. and S. Ishikiriyama, Clinical and cytogenetic studies of the Prader-Willi syndrome: evidence of phenotype-karyotype correlation. Hum Genet, 1985. 69(1): p. 22-7.

236. Ohman Forslund, K. and K. Nordqvist, The melanoma antigen genes--any clues to their functions in normal tissues? Exp Cell Res, 2001. 265(2): p. 185-94.

237. Muscatelli, F., et al., Disruption of the mouse Necdin gene results in hypothalamic and behavioral alterations reminiscent of the human Prader-Willi syndrome. Hum Mol Genet, 2000. 9(20): p. 3101-10.

238. Swaab, D.F., J.S. Purba, and M.A. Hofman, Alterations in the hypothalamic paraventricular nucleus and its oxytocin neurons (putative satiety cells) in Prader-Willi syndrome: a study of five cases. J Clin Endocrinol Metab, 1995. 80(2): p. 573-9.

239. Nagai, T., et al., Prader-Willi syndrome with elevated follicle stimulating hormone levels and diabetes mellitus. Intern Med, 1998. 37(12): p. 1039-41.

240. Pelleymounter, M.A., M.J. Cullen, and C.L. Wellman, Characteristics of BDNF-induced weight loss. Exp Neurol, 1995. 131(2): p. 229-38.

241. Kernie, S.G., D.J. Liebl, and L.F. Parada, BDNF regulates eating behavior and locomotor activity in mice. Embo J, 2000. 19(6): p. 1290-1300.

242. Lyons, W.E., L.A. Mamounas, and G.A. Ricaurte, Brain-derived neurotropic factor-deficient mice develop aggressiveness and hyperphagia in conjunction with brain serotonergic abnormalities. Proc Natl Acad Sci U S A, 1999. 96: p. 15239-15244.

243. Rios, M., et al., Conditional deletion of brain-derived neurotropic factor in the postnatal brain leads to obesity and hyperactivity. Mol Endocrinol, 2001. 15(10): p. 1748-1757.

244. Lyons, W.E., et al., Brain-derived neurotrophic factor-deficient mice develop aggressiveness and hyperphagia in conjunction with brain serotonergic abnormalities. Proc Natl Acad Sci U S A, 1999. 96(26): p. 15239-44.

245. Inoue, K., et al., Bromocriptine enhances feeding behavior without changing dopamine metabolism. Pharmacol Biochem Behav, 1997. 58(1): p. 183-8.

246. Salamone, J.D., M.J. Zigmond, and E.M. Stricker, Characterization of the impaired feeding behavior in rats given haloperidol or dopamine-depleting brain lesions. Neuroscience, 1990. 39(1): p. 17-24.

247. Scislowski, P.W., et al., Biochemical mechanisms responsible for the attenuation of diabetic and obese conditions in ob/ob mice treated with dopaminergic agonists. Int J Obes Relat Metab Disord, 1999. 23(4): p. 425-31.

248. Thomas, S.A. and R.D. Palmiter, Thermoregulatory and metabolic phenotypes of mice lacking noradrenaline and adrenaline. Nature, 1997. 387(6628): p. 94-7.

249. Zhou, Q.Y. and R.D. Palmiter, Dopamine-deficient mice are severely hypoactive, adipsic, and aphagic. Cell, 1995. 83(7): p. 1197-209.

250. Tyrka, A. and G.P. Smith, Potency of SCH 23390 for decreasing sucrose intake in rat pups depends on mode of ingestion. Pharmacol Biochem Behav, 1991. 39(4): p. 955-61.

251. Sakata, I., et al., Ghrelin-producing cells exist as two types of cells, closed- and opened-type cells, in the rat gastrointestinal tract. Peptides, 2002. 23(3): p. 531-6.

252. Tschop, M., D.L. Smiley, and M.L. Heiman, Ghrelin induces adiposity in rodents. Nature, 2000. 407(6806): p. 908-13.

253. Kojima, M., et al., Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature, 1999. 402(6762): p. 656-60.

254. Cummings, D.E., et al., A preprandial rise in plasma ghrelin levels suggests a role in meal initiation in humans. Diabetes, 2001. 50(8): p. 1714-9.

255. Date, Y., et al., The role of the gastric afferent vagal nerve in ghrelin-induced feeding and growth hormone secretion in rats. Gastroenterology, 2002. 123(4): p. 1120-8.

256. Willesen, M.G., P. Kristensen, and J. Romer, Co-localization of growth hormone secretagogue receptor and NPY mRNA in the arcuate nucleus of the rat. Neuroendocrinology, 1999. 70(5): p. 306-16.

257. Cummings, D.E., et al., Elevated plasma ghrelin levels in Prader Willi syndrome. Nat Med, 2002. 8(7): p. 643-4.

258. Cummings, D.E., et al., Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery. N Engl J Med, 2002. 346(21): p. 1623-30.

259. Sun, Y. and S. Ahmed. Generation and characterization of ghrelin knockout mouse. in The Endocrine Society's 84th Annual Meeting. 2002. San Francisco.

260. Bray, G.A., Afferent signals regulating food intake. Proc Nutr Soc, 2000. 59(3): p. 373-84.

261. Moran, T.H., et al., Disordered food intake and obesity in rats lacking cholecystokinin A receptors. Am J Physiol, 1998. 274(3 Pt 2): p. R618-25.

262. Funakoshi, A., et al., Little or no expression of the cholecystokinin-A receptor gene in the pancreas of diabetic rats (Otsuka Long-Evans Tokushima Fatty = OLETF rats). Biochem Biophys Res Commun, 1994. 199(2): p. 482-8.

263. Otsuki, M., et al., Loss of sensitivity to cholecystokinin stimulation of isolated pancreatic acini from genetically diabetic rats. Am J Physiol, 1995. 268(3 Pt 1): p. E531-6.

264. Flynn, M.C., et al., Mode of action of OB protein (leptin) on feeding. Amer J Physiol, 1998. 275(44): p. R174-R179.

265. Funakoshi, A., et al., Gene structure of human cholecystokinin (CCK) type-A receptor: body fat content is related to CCK type-A receptor gene promoter polymorphism. FEBS Lett, 2000. 466(2-3): p. 264-6.

266. Lacourse, K.A., et al., Pancreatic function in CCK-deficient mice: adaptation to dietary protein does not require CCK. Am J Physiol, 1999. 276(5 Pt 1): p. G1302-9.

267. Turton, M.D., et al., A role for glucagon-like peptide-1 in the central regulation of feeding. Nature, 1996. 379: p. 69-72.

268. Scrocchi, L.A., et al., Glucose intolerance but normal satiety in mice with a null mutation in the glucagon-like peptide 1 receptor gene. Nat Med, 1996. 2(11): p. 1254-8.

269. Flint, A., et al., Glucagon-like peptide 1 promotes satiety and suppresses energy intake in humans. J Clin Invest, 1998. 101(3): p. 515-20.

270. Gutzwiller, J.P., et al., Glucagon-like peptide-1 promotes satiety and reduces food intake in patients with diabetes mellitus type 2. Am J Physiol, 1999. 276(5 Pt 2): p. R1541-4.

271. Gutzwiller, J.P., et al., Glucagon-like peptide-1: a potent regulator of food intake in humans. Gut, 1999. 44(1): p. 81-6.

272. Zander, M., S. Madsbad, and J.J. Jolst, GLP-1 for six weeks reduces body weight and improves insulin sensitivity and glycemic control in patients with Type 2 diabetes. Diabetes, 2001. 50(Suppl. 2): p. A31.

273. Hamann, A., J.S. Flier, and B.B. Lowell, Obesity after genetic ablation of brown adipose tissue. Z Ernahrungswiss, 1998. 37(Suppl 1): p. 1-7.

274. Melnyk, A., M.E. Harper, and J. Himms-Hagen, Raising at thermoneutrality prevents obesity and hyperphagia in BAT- ablated transgenic mice. Am J Physiol, 1997. 272(4 Pt 2): p. R1088-93.

275. Enerback, S., et al., Mice lacking mitochondrial uncoupling protein are cold-sensitive but not obese. Nature, 1997. 387(6628): p. 90-4.

276. Fleury, C., et al., Uncoupling protein-2: a novel gene linked to obesity and hyperinsulinemia. Nat Genet, 1997. 15(3): p. 269-72.

277. Gimeno, R.E., et al., Cloning and characterization of an uncoupling protein homolog: a potential molecular mediator of human thermogenesis. Diabetes, 1997. 46(5): p. 900-6.

278. Zhou, Y.T., et al., Induction by leptin of uncoupling protein-2 and enzymes of fatty acid oxidation. Proc Natl Acad Sci U S A, 1997. 94(12): p. 6386-90.

279. Richard, D., et al., Distribution of the uncoupling protein 2 mRNA in the mouse brain. J Comp Neurol, 1998. 397(4): p. 549-60.

280. Horvath, T.L., et al., Brain uncoupling protein 2: uncoupled neuronal mitochondria predict thermal synapses in homeostatic centers. J Neurosci, 1999. 19(23): p. 10417-27.

281. Arsenijevic, D., et al., Disruption of the uncoupling protein-2 gene in mice reveals a role in immunity and reactive oxygen species production. Nat Genet, 2000. 26(4): p. 435-9.

282. Zhang, C.Y., et al., Uncoupling protein-2 negatively regulates insulin secretion and is a major link between obesity, beta cell dysfunction, and type 2 diabetes. Cell, 2001. 105(6): p. 745-55.

283. Joseph, J.W., et al., Uncoupling protein 2 knockout mice have enhanced insulin secretory capacity after a high-fat diet. Diabetes, 2002. 51(11): p. 3211-9.

284. Boss, O., et al., Uncoupling protein-3: a new member of the mitochondrial carrier family with tissue-specific expression. FEBS-Lett., 1997. 408: p. 39-42.

285. Vidal-Puig, A.J., et al., Energy metabolism in uncoupling protein 3 gene knockout mice. J Biol Chem, 2000. 275(21): p. 16258-66.

286. Cadenas, S., et al., The basal proton conductance of skeletal muscle mitochondria from transgenic mice overexpressing or lacking uncoupling protein-3. J Biol Chem, 2002. 277(4): p. 2773-8.

287. Clapham, J.C., et al., Mice overexpressing human uncoupling protein-3 in skeletal muscle are hyperphagic and lean. Nature, 2000. 406(6794): p. 415-8.

288. Hesselink, M.K., et al., Increased uncoupling protein 3 content does not affect mitochondrial function in human skeletal muscle in vivo. J Clin Invest, 2003. 111(4): p. 479-86.

289. Millet, L., et al., Increased uncoupling protein-2 and -3 mRNA expression during fasting in obese and lean humans. J Clin Invest, 1997. 100(11): p. 2665-70.

290. Oppert, J.M., et al., DNA polymorphism in the uncoupling protein (UCP) gene and human body fat. Int J Obes Relat Metab Disord, 1994. 18(8): p. 526-31.

291. Clement, K., et al., Additive effect of A-->G (-3826) variant of the uncoupling protein gene and the Trp64Arg mutation of the beta 3-adrenergic receptor gene on weight gain in morbid obesity. Int J Obes Relat Metab Disord, 1996. 20(12): p. 1062-6.

292. Esterbauer, H., et al., A common polymorphism in the promoter of UCP2 is associated with decreased risk of obesity in middle-aged humans. Nat Genet, 2001. 28(2): p. 178-83.

293. Chung, W.K., et al., Genetic and physiologic analysis of the role of uncoupling protein 3 in human energy homeostasis. Diabetes, 1999. 48(9): p. 1890-5.

294. Otabe, S., et al., Mutation screening and association studies of the human uncoupling protein 3 gene in normoglycemic and diabetic morbidly obese patients. Diabetes, 1999. 48(1): p. 206-8.

295. Argyropoulos, G., et al., Effects of mutations in the human uncoupling protein 3 gene on the respiratory quotient and fat oxidation in severe obesity and type 2 diabetes. J Clin Invest, 1998. 102(7): p. 1345-51.

296. Brown, A.M., et al., Endogenous mutations in human uncoupling protein 3 alter its functional properties. FEBS Lett, 1999. 464(3): p. 189-93.

297. Krief, S., et al., Tissue distribution of beta 3-adrenergic receptor mRNA in man. J Clin Invest, 1993. 91(1): p. 344-9.

298. Thomas, R.F. and S.B. Liggett, Lack of beta 3-adrenergic receptor mRNA expression in adipose and other metabolic tissues in the adult human. Mol Pharmacol, 1993. 43(3): p. 343-8.

299. Chamberlain, P.D., et al., The tissue distribution of the human beta3-adrenoceptor studied using a monoclonal antibody: direct evidence of the beta3-adrenoceptor in human adipose tissue, atrium and skeletal muscle. Int J Obes Relat Metab Disord, 1999. 23(10): p. 1057-65.

300. Clement, K., et al., Genetic variation in the beta 3-adrenergic receptor and an increased capacity to gain weight in patients with morbid obesity. N Engl J Med, 1995. 333(6): p. 352-4.

301. Walston, J., et al., Time of onset of non-insulin-dependent diabetes mellitus and genetic variation in the beta 3-adrenergic-receptor gene. N Engl J Med, 1995. 333(6): p. 343-7.

302. Widen, E., et al., Association of a polymorphism in the beta 3-adrenergic-receptor gene with features of the insulin resistance syndrome in Finns. N Engl J Med, 1995. 333(6): p. 348-51.

303. Buettner, R., et al., The Trp64Arg polymorphism of the beta 3-adrenergic receptor gene is not associated with obesity or type 2 diabetes mellitus in a large population-based Caucasian cohort. J Clin Endocrinol Metab, 1998. 83(8): p. 2892-7.

304. Gagnon, J., et al., The Trp64Arg mutation of the beta3 adrenergic receptor gene has no effect on obesity phenotypes in the Quebec Family Study and Swedish Obese Subjects cohorts. J Clin Invest, 1996. 98(9): p. 2086-93.

305. Nagase, T., et al., Lack of association between the Trp64 Arg mutation in the beta 3-adrenergic receptor gene and obesity in Japanese men: a longitudinal analysis. J Clin Endocrinol Metab, 1997. 82(4): p. 1284-7.

306. Weyer, C., et al., Increase in insulin action and fat oxidation after treatment with CL 316,243, a highly selective beta3-adrenoceptor agonist in humans. Diabetes, 1998. 47(10): p. 1555-61.

307. de Souza, C.J. and B.F. Burkey, Beta 3-adrenoceptor agonists as anti-diabetic and anti-obesity drugs in humans. Curr Pharm Des, 2001. 7(14): p. 1433-49.

308. Susulic, V.S., et al., Targeted disruption of the b3-adrenergic receptor gene. J Biol Chem, 1995. 270(49): p. 29483-29492.

309. Chruscinski, A.J., et al., Targeted disruption of the beta2 adrenergic receptor gene. J Biol Chem, 1999. 274(24): p. 16694-700.

310. Rohrer, D.K., et al., Cardiovascular and metabolic alterations in mice lacking both beta1- and beta2-adrenergic receptors. J Biol Chem, 1999. 274(24): p. 16701-8.

311. Bachman, E.S., et al., betaAR signaling required for diet-induced thermogenesis and obesity resistance. Science, 2002. 297(5582): p. 843-5.

312. Cummings, D.E., et al., Genetically lean mice result from targeted disruption of the RIIß subunit of protein kinase A. Nature, 1996. 382: p. 622-626.

313. Schreyer, S.A., et al., Mutation of the RIIbeta subunit of protein kinase A prevents diet- induced insulin resistance and dyslipidemia in mice. Diabetes, 2001. 50(11): p. 2555-62.

314. Rothwell, N.J. and M.J. Stock, A role for brown adipose tissue in diet-induced thermogenesis. Nature, 1979. 281(5726): p. 31-5.

315. McGregor, I.S., et al., Prefrontal cortex alpha 2 adrenoceptors and energy balance. Brain Res Bull, 1991. 26(5): p. 683-91.

316. He, Y., et al., The mouse obese gene. Genomic organization, promoter activity, and activation by CCAAT/enhancer-binding protein alpha. J Biol Chem, 1995. 270(48): p. 28887-91.

317. Hwang, C.S., et al., Transcriptional activation of the mouse obese (ob) gene by CCAAT/enhancer binding protein alpha. Proc Natl Acad Sci U S A, 1996. 93(2): p. 873-7.

318. Miller, S.G., et al., The adipocyte specific transcription factor C/EBPalpha modulates human ob gene expression. Proc Natl Acad Sci U S A, 1996. 93(11): p. 5507-11.

319. Wang, N.D., et al., Impaired energy homeostasis in C/EBP alpha knockout mice. Science, 1995. 269(5227): p. 1108-12.

320. Flodby, P., et al., Increased hepatic cell proliferation and lung abnormalities in mice deficient in CCAAT/enhancer binding protein alpha. J Biol Chem, 1996. 271(40): p. 24753-60.

321. Tanaka, T., et al., Defective adipocyte differentiation in mice lacking the C/EBPbeta and/or C/EBPdelta gene. Embo J, 1997. 16(24): p. 7432-43.

322. Ross, S.R., R.A. Graves, and B.M. Spiegelman, Targeted expression of a toxin gene to adipose tissue: transgenic mice resistant to obesity. Genes Dev, 1993. 7(7B): p. 1318-24.

323. Moitra, J., et al., Life without white fat: a transgenic mouse. Genes Dev, 1998. 12(20): p. 3168-81.

324. Garg, A., et al., A gene for congenital generalized lipodystrophy maps to human chromosome 9q34. J Clin Endocrinol Metab, 1999. 84(9): p. 3390-4.

325. Magre, J., et al., Identification of the gene altered in Berardinelli-Seip congenital lipodystrophy on chromosome 11q13. Nat Genet, 2001. 28(4): p. 365-70.

326. Gavrilova, O., et al., Surgical implantation of adipose tissue reverses diabetes in lipoatrophic mice. J Clin Invest, 2000. 105(3): p. 271-8.

327. Colombo, C., et al., Transplantation of adipose tissue lacking leptin is unable to reverse the metabolic abnormalities associated with lipoatrophy. Diabetes, 2002. 51(9): p. 2727-33.

328. Ebihara, K., et al., Transgenic overexpression of leptin rescues insulin resistance and diabetes in a mouse model of lipoatrophic diabetes. Diabetes, 2001. 50(6): p. 1440-8.

329. Petersen, K.F., et al., Leptin reverses insulin resistance and hepatic steatosis in patients with severe lipodystrophy. J Clin Invest, 2002. 109(10): p. 1345-50.

330. Costet, P., et al., Peroxisome proliferator-activated receptor alpha-isoform deficiency leads to progressive dyslipidemia with sexually dimorphic obesity and steatosis. J Biol Chem, 1998. 273(45): p. 29577-85.

331. Kersten, S., et al., Peroxisome proliferator-activated receptor alpha mediates the adaptive response to fasting. J Clin Invest, 1999. 103(11): p. 1489-98.

332. Muoio, D.M., et al., Fatty acid homeostasis and induction of lipid regulatory genes in skeletal muscles of peroxisome proliferator-activated receptor (PPAR) alpha knock-out mice. Evidence for compensatory regulation by PPAR delta. J Biol Chem, 2002. 277(29): p. 26089-97.

333. Kubota, N., et al., PPAR gamma mediates high-fat diet-induced adipocyte hypertrophy and insulin resistance. Mol Cell, 1999. 4(4): p. 597-609.

334. Miles, P.D., et al., Improved insulin-sensitivity in mice heterozygous for PPAR-gamma deficiency. J Clin Invest, 2000. 105(3): p. 287-92.

335. Hara, K., et al., The Pro12Ala polymorphism in PPAR gamma2 may confer resistance to type 2 diabetes. Biochem Biophys Res Commun, 2000. 271(1): p. 212-6.

336. Altshuler, D., et al., The common PPARgamma Pro12Ala polymorphism is associated with decreased risk of type 2 diabetes. Nat Genet, 2000. 26(1): p. 76-80.

337. Deeb, S.S., et al., A Pro12Ala substitution in PPARgamma2 associated with decreased receptor activity, lower body mass index and improved insulin sensitivity. Nat Genet, 1998. 20(3): p. 284-7.

338. Yamauchi, T., et al., Increased insulin sensitivity despite lipodystrophy in Crebbp heterozygous mice. Nat Genet, 2002. 30(2): p. 221-6.

339. Hotamisligil, G.S., et al., Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance. J Clin Invest, 1995. 95(5): p. 2409-15.

340. Kern, P.A., et al., Adipose tissue tumor necrosis factor and interleukin-6 expression in human obesity and insulin resistance. Am J Physiol Endocrinol Metab, 2001. 280(5): p. E745-51.

341. Hotamisligil, G.S., The role of TNFalpha and TNF receptors in obesity and insulin resistance. J Intern Med, 1999. 245(6): p. 621-5.

342. Hotamisligil, G.S., N.S. Shargill, and B.M. Spiegelman, Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science, 1993. 259(5091): p. 87-91.

343. Ventre, J., et al., Targeted disruption of the tumor necrosis factor-alpha gene: metabolic consequences in obese and nonobese mice. Diabetes, 1997. 46(9): p. 1526-31.

344. Uysal, K.T., et al., Protection from obesity-induced insulin resistance in mice lacking TNF- alpha function. Nature, 1997. 389(6651): p. 610-4.

345. Schreyer, S.A., S.C. Chua, Jr., and R.C. LeBoeuf, Obesity and diabetes in TNF-alpha receptor- deficient mice. J Clin Invest, 1998. 102(2): p. 402-11.

346. Zhou, X., et al., Mutation responsible for the mouse pygmy phenotype in the developmentally regulated factor HMGI-C. Nature, 1995. 376(6543): p. 771-4.

347. Ashar, H.R., et al., Disruption of the architectural factor HMGI-C: DNA-binding AT hook motifs fused in lipomas to distinct transcriptional regulatory domains. Cell, 1995. 82(1): p. 57-65.

348. Anand, A. and K. Chada, In vivo modulation of Hmgic reduces obesity. Nat Genet, 2000. 24(4): p. 377-80.

349. Benson, K.F. and K. Chada, Mini-mouse: phenotypic characterization of a transgenic insertional mutant allelic to pygmy. Genet Res, 1994. 64(1): p. 27-33.

350. Shimomura, I., et al., Insulin resistance and diabetes mellitus in transgenic mice expressing nuclear SREBP-1c in adipose tissue: model for congenital generalized lipodystrophy. Genes Dev, 1998. 12(20): p. 3182-94.

351. Zhang, Y., et al., Determinants of leptin gene expression in fat depots of lean mice. Am J Physiol Regul Integr Comp Physiol, 2002. 282(1): p. R226-34.

352. Shimomura, I., et al., Leptin reverses insulin resistance and diabetes mellitus in mice with congenital lipodystrophy. Nature, 1999. 401(6748): p. 73-6.

353. Smith, S.J., et al., Obesity resistance and multiple mechanisms of triglyceride synthesis in mice lacking Dgat. Nat Genet, 2000. 25(1): p. 87-90.

354. Chen, H.C., et al., Increased insulin and leptin sensitivity in mice lacking acyl CoA:diacylglycerol acyltransferase 1. J Clin Invest, 2002. 109(8): p. 1049-55.

355. Cases, S., et al., Cloning of DGAT2, a second mammalian diacylglycerol acyltransferase, and related family members. J Biol Chem, 2001. 276(42): p. 38870-6.

356. Abu-Elheiga, L., et al., Continuous fatty acid oxidation and reduced fat storage in mice lacking acetyl-CoA carboxylase 2. Science, 2001. 291(5513): p. 2613-6.

357. Loftus, T.M., et al., Reduced food intake and body weight in mice treated with fatty acid synthase inhibitors. Science, 2000. 288(5475): p. 2379-81.

358. Okazaki, H., et al., Lipolysis in the absence of hormone-sensitive lipase: evidence for a common mechanism regulating distinct lipases. Diabetes, 2002. 51(12): p. 3368-75.

359. Clifford, G.M., et al., Translocation of hormone-sensitive lipase and perilipin upon lipolytic stimulation of rat adipocytes. J Biol Chem, 2000. 275(7): p. 5011-5.

360. Martinez-Botas, J., et al., Absence of perilipin results in leanness and reverses obesity in Leprdb/db mice. Nat Gen, 2000. 26: p. 474-479.

361. Tansey, J.T., et al., Perilipin ablation results in a lean mouse with aberrant adipocyte lipolysis, enhanced leptin production, and resistance to diet-induced obesity. Proc Natl Acad Sci U S A, 2001. 98(11): p. 6494-6499.

362. McPherron, A.C. and S.J. Lee, Double muscling in cattle due to mutations in the myostatin gene. Proc Natl Acad Sci U S A, 1997. 94(23): p. 12457-61.

363. McPherron, A.C., A.M. Lawler, and S.J. Lee, Regulation of skeletal muscle mass in mice by a new TGF-beta superfamily member. Nature, 1997. 387(6628): p. 83-90.

364. McPherron, A.C. and S.J. Lee, Suppression of body fat accumulation in myostatin-deficient mice. J Clin Invest, 2002. 109(5): p. 595-601.

365. Kim, H.S., et al., Inhibition of preadipocyte differentiation by myostatin treatment in 3T3-L1 cultures. Biochem Biophys Res Commun, 2001. 281(4): p. 902-6.

366. Pomp, D., Genetic dissection of obesity in polygenic animal models. Behav Genet, 1997. 27(4): p. 285-306.

367. Anunciado, R.V., et al., Quantitative trait loci for body weight in the intercross between SM/J and A/J mice. Exp Anim, 2001. 50(4): p. 319-24.

368. Brockmann, G.A., et al., Single QTL effects, epistasis, and pleiotropy account for two-thirds of the phenotypic F(2) variance of growth and obesity in DU6i x DBA/2 mice. Genome Res, 2000. 10(12): p. 1941-57.

369. Inoue, H., et al., Human cholecystokinin type A receptor gene: cytogenetic localization, physical mapping, and identification of two missense variants in patients with obesity and non-insulin-dependent diabetes mellitus (NIDDM). Genomics, 1997. 42(2): p. 331-5.

370. Miller, L.J., et al., Abnormal processing of the human cholecystokinin receptor gene in association with gallstones and obesity. Gastroenterology, 1995. 109(4): p. 1375-80.

371. Corva, P.M., S. Horvat, and J.F. Medrano, Quantitative trait loci affecting growth in high growth (hg) mice. Mamm Genome, 2001. 12(4): p. 284-90.

372. Lembertas, A.V., et al., Identification of an obesity quantitative trait locus on mouse chromosome 2 and evidence of linkage to body fat and insulin on the human homologous region 20q. J Clin Invest, 1997. 100(5): p. 1240-7.

373. Cool, D.R., et al., Carboxypeptidase E is a regulated secretory pathway sorting receptor: genetic obliteration leads to endocrine disorders in Cpe(fat) mice. Cell, 1997. 88(1): p. 73-83.

374. Brockmann, G., et al., Detection of QTL for body weight and body fat content in mice using genetic markers. J Anim Breed Genet, 1996. 113: p. 373-379.

375. Keightley, P.D., et al., Test of candidate gene--quantitative trait locus association applied to fatness in mice. Heredity, 1998. 81 ( Pt 6): p. 630-7.

376. Dobson, M.G., et al., The N363S polymorphism of the glucocorticoid receptor: potential contribution to central obesity in men and lack of association with other risk factors for coronary heart disease and diabetes mellitus. J Clin Endocrinol Metab, 2001. 86(5): p. 2270-4.

377. Vaughn, T.T., et al., Mapping quantitative trait loci for murine growth: a closer look at genetic architecture. Genet Res, 1999. 74(3): p. 313-22.

378. Cheverud, J.M., et al., Quantitative trait loci for murine growth. Genetics, 1996. 142(4): p. 1305-19.

379. Cheverud, J.M., et al., Genetic architecture of adiposity in the cross of LG/J and SM/J inbred mice. Mamm Genome, 2001. 12(1): p. 3-12.

380. Suto, J., et al., Genetics of obesity in KK mouse and effects of A(y) allele on quantitative regulation. Mamm Genome, 1998. 9(7): p. 506-10.

381. Scrocchi, L.A., et al., Elimination of glucagon-like peptide 1R signaling does not modify weight gain and islet adaptation in mice with combined disruption of leptin and GLP-1 action. Diabetes, 2000. 49(9): p. 1552-60.

382. Keightley, P.D., et al., A genetic map of quantitative trait loci for body weight in the mouse. Genetics, 1996. 142(1): p. 227-35.

383. Osuga, J., et al., Targeted disruption of hormone-sensitive lipase results in male sterility and adipocyte hypertrophy, but not in obesity. Proc Natl Acad Sci U S A, 2000. 97(2): p. 787-92.

384. Li, P., et al., Mice deficient in IL-1 beta-converting enzyme are defective in production of mature IL-1 beta and resistant to endotoxic shock. Cell, 1995. 80(3): p. 401-11.

385. Saltiel, A.R., New perspectives into the molecular pathogenesis and treatment of type 2 diabetes. Cell, 2001. 104(4): p. 517-29.

386. Warden, C.H., et al., Identification of four chromosomal loci determining obesity in a multifactorial mouse model. J Clin Invest, 1995. 95(4): p. 1545-52.

387. Strobel, A., et al., A leptin missense mutation associated with hypogonadism and morbid obesity. Nat Genet, 1998. 18(3): p. 213-5.

388. Clement, K., Leptin and the genetics of obesity. Acta Paediatr Suppl, 1999. 88(428): p. 51-7.

389. Clement, K., et al., A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction [see comments]. Nature, 1998. 392(6674): p. 398-401.

390. Yeo, G.S., et al., A frameshift mutation in MC4R associated with dominantly inherited human obesity. Nat Genet, 1998. 20(2): p. 111-2.

391. Vaisse, C., et al., A frameshift mutation in human MC4R is associated with a dominant form of obesity. Nature Genetics, 1998. 20: p. 113-114.

392. Hinney, A., et al., Several mutations in the melanocortin-4 receptor gene including a nonsense and a frameshift mutation associated with dominantly inherited obesity in humans. J Clin Endocrinol Metab, 1999. 84(4): p. 1483-6.

393. Collins, A.C., I.C. Martin, and B.W. Kirkpatrick, Growth quantitative trait loci (QTL) on mouse chromosome 10 in a Quackenbush-Swiss x C57BL/6J backcross. Mamm Genome, 1993. 4(8): p. 454-8.

394. Good, D.J., et al., Hypogonadism and obesity in mice with a targeted deletion of the Nhlh2 gene. Nat Genet, 1997. 15(4): p. 397-401.

395. Moody, D.E., et al., Identification of quantitative trait loci influencing traits related to energy balance in selection and inbred lines of mice. Genetics, 1999. 152(2): p. 699-711.

396. Horvat, S., et al., Mapping of obesity QTLs in a cross between mouse lines divergently selected on fat content. Mamm Genome, 2000. 11(1): p. 2-7.

397. Clement, K., et al., A sib-pair analysis study of 15 candidate genes in French families with morbid obesity: indication for linkage with islet 1 locus on chromosome 5q. Diabetes, 1999. 48(2): p. 398-402.

398. MacDonald, H.R. and R. Wevrick, The necdin gene is deleted in Prader-Willi syndrome and is imprinted in human and mouse. Hum Mol Genet, 1997. 6(11): p. 1873-8.

399. Butler, M.G. and B.B. Jenkins, Analysis of chromosome breakage in the Prader-Labhart-Willi syndrome. Am J Med Genet, 1989. 32(4): p. 514-9.

400. Nicholls, R.D., et al., Genetic imprinting suggested by maternal heterodisomy in nondeletion Prader-Willi syndrome. Nature, 1989. 342(6247): p. 281-5.

401. Buiting, K., et al., Molecular definition of the Prader-Willi syndrome chromosome region and orientation of the SNRPN gene. Hum Mol Genet, 1993. 2(12): p. 1991-4.

402. Yang, T., et al., A mouse model for Prader-Willi syndrome imprinting-centre mutations. Nat Genet, 1998. 19(1): p. 25-31.

403. Boggon, T.J., et al., Implication of tubby proteins as transcription factors by structure-based functional analysis. Science, 1999. 286(5447): p. 2119-25.

404. Zhou, Q.Y., C.J. Quaife, and R.D. Palmiter, Targeted disruption of the tyrosine hydroxylase gene reveals that catecholamines are required for mouse fetal development. Nature, 1995. 374(6523): p. 640-3.

405. Smith, S.J., et al., Obesity resistance and multiple mechanisms of triglyceride synthesis in mice lacking Dgat. Nat Genet, 2000. 25(1): p. 87-90.

406. Chen, H.C., et al., Leptin modulates the effects of acyl CoA:diacylglycerol acyltransferase deficiency on murine fur and sebaceous glands. J Clin Invest, 2002. 109(2): p. 175-81.

407. Chen, H.C., Z. Ladha, and R.V. Farese, Jr., Deficiency of acyl coenzyme a:diacylglycerol acyltransferase 1 increases leptin sensitivity in murine obesity models. Endocrinology, 2002. 143(8): p. 2893-8.

408. Chen, H.C., et al., Analysis of energy expenditure at different ambient temperatures in mice lacking DGAT1. Am J Physiol Endocrinol Metab, 2003. 284(1): p. E213-8.

409. Chen, H.C., et al., Dissociation of obesity and impaired glucose disposal in mice overexpressing acyl coenzyme a:diacylglycerol acyltransferase 1 in white adipose tissue. Diabetes, 2002. 51(11): p. 3189-95.

410. Tanomura, H., et al., Detection of a quantitative trait locus for intramuscular fat accumulation using the OLETF rat. J Vet Med Sci, 2002. 64(1): p. 45-50.

411. Mehrabian, M., et al., Genetic loci controlling body fat, lipoprotein metabolism, and insulin levels in a multifactorial mouse model. J Clin Invest, 1998. 101(11): p. 2485-96.

412. Dragani, T.A., et al., Mapping of body weight loci on mouse chromosome X. Mamm Genome, 1995. 6(11): p. 778-81.

413. Taylor, B.A., L.M. Tarantino, and S.J. Phillips, Gender-influenced obesity QTLs identified in a cross involving the KK type II diabetes-prone mouse strain. Mamm Genome, 1999. 10(10): p. 963-8.

414. Ishikawa, A., Y. Matsuda, and T. Namikawa, Detection of quantitative trait loci for body weight at 10 weeks from Philippine wild mice. Mamm Genome, 2000. 11(10): p. 824-30.

415. Chen, H., et al., Evidence that the diabetes gene encodes the leptin receptor: identification of a mutation im the leptin receptor gene in db/db mice. Cell, 1996. 84: p. 491-495.

416. Barsh, G.S., I.S. Farooqi, and S. O'Rahilly, Genetics of body-weight regulation. Nature, 2000. 404(6778): p. 644-51.