1. Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM. Positional cloning of the mouse obese gene and its human homologue. Nature. 372:425-432. 1994.

2. Lee GH, Proenca R, Montez JM, Carroll KM, Darvishzadeh JG, Lee JI, Friedman JM. Abnormal splicing of the leptin receptor in diabetic mice. Nature. 379:632-635. 1996.

3. Himms-Hagen J. Brown adipose tissue thermogenesis and obesity. Prog Lipid Res. 28:67-115. 1989.

4. Ravussin E, Lillioja S, Anderson TE, Christin L, Bogardus C. Determinants of 24-hour energy expenditure in man. Methods and results using a respiratory chamber. J Clin Invest. 78:1568-1578. 1986.

5. Schoeller DA, van Santen E. Measurement of energy expenditure in humans by doubly labeled water method. J Appl Physiol. 53:955-959. 1982.

6. Ravussin E, Lillioja S, Knowler WC, Christin L, Freymond D, Abbott WG, Boyce V, Howard BV, Bogardus C. Reduced rate of energy expenditure as a risk factor for body-weight gain. N Engl J Med. 318:467-472. 1988.

7. Bouchard C, Tremblay A, Despres JP, Nadeau A, Lupien PJ, Theriault G, Dussault J, Moorjani S, Pinault S, Fournier G. The response to long-term overfeeding in identical twins. N Engl J Med. 322:1477-1482. 1990.

8. Levine JA, Eberhardt NL, Jensen MD. Role of nonexercise activity thermogenesis in resistance to fat gain in humans. Science. 283:212-214. 1999.

9. Leibel RL, Rosenbaum M, Hirsch J. Changes in energy expenditure resulting from altered body weight. N Engl J Med. 332:621-628. 1995.

10. Rolfe DF, Brown GC. Cellular energy utilization and molecular origin of standard metabolic rate in mammals. Physiol Rev. 77:731-758. 1997.

11. Nicholls DG, Locke RM. Thermogenic mechanisms in brown fat. Physiol Rev. 64:1-64. 1984.

12. Enerback S, Jacobsson A, Simpson EM, Guerra C, Yamashita H, Harper ME, Kozak LP. Mice lacking mitochondrial uncoupling protein are cold-sensitive but not obese. Nature. 387:90-94. 1997.

13. Denborough M. Malignant hyperthermia. Lancet. 352:1131-1136. 1998.

14. Elmquist JK, Elias CF, Saper CB. From lesions to leptin: hypothalamic control of food intake and body weight. Neuron. 22:221-232. 1999.

15. Elmquist JK. Hypothalamic pathways underlying the endocrine, autonomic, and behavioral effects of leptin. Int J Obes Relat Metab Disord. 25:S78-82. 2001.

16. Huszar D, Lynch CA, Fairchild-Huntress V, Dunmore JH, Fang Q, Berkemeier LR, Gu W, Kesterson RA, Boston BA, Cone RD, Smith FJ, Campfield LA, Burn P, Lee F. Targeted disruption of the melanocortin-4 receptor results in obesity in mice. Cell. 88:131-141. 1997.

17. Butler AA, Marks DL, Fan W, Kuhn CM, Bartolome M, Cone RD. Melanocortin-4 receptor is required for acute homeostatic responses to increased dietary fat. Nat Neurosci. 4:605-611. 2001.

18. Thomas SA, Palmiter RD. Thermoregulatory and metabolic phenotypes of mice lacking noradrenaline and adrenaline [see comments]. Nature. 387:94-97. 1997.

19. Himms-Hagen J, Cui J, Danforth E, Jr., Taatjes DJ, Lang SS, Waters BL, Claus TH. Effect of CL-316,243, a thermogenic beta 3-agonist, on energy balance and brown and white adipose tissues in rats. Am J Physiol. 266:R1371-1382. 1994.

20. Ito M, Grujic D, Abel ED, Vidal-Puig A, Susulic VS, Lawitts J, Harper ME, Himms-Hagen J, Strosberg AD, Lowell BB. Mice expressing human but not murine beta3-adrenergic receptors under the control of human gene regulatory elements. Diabetes. 47:1464-1471. 1998.

21. Arch JR, Ainsworth AT, Cawthorne MA, Piercy V, Sennitt MV, Thody VE, Wilson C, Wilson S. Atypical beta-adrenoceptor on brown adipocytes as target for anti- obesity drugs. Nature. 309:163-165. 1984.

22. Grujic D, Susulic VS, Harper ME, Himms-Hagen J, Cunningham BA, Corkey BE, Lowell BB. Beta3-adrenergic receptors on white and brown adipocytes mediate beta3-selective agonist-induced effects on energy expenditure, insulin secretion, and food intake. A study using transgenic and gene knockout mice. J Biol Chem. 272:17686-17693. 1997.

23. Zurlo F, Larson K, Bogardus C, Ravussin E. Skeletal muscle metabolism is a major determinant of resting energy expenditure. J Clin Invest. 86:1423-1427. 1990.

24. Simonsen L, Bulow J, Madsen J, Christensen NJ. Thermogenic response to epinephrine in the forearm and abdominal subcutaneous adipose tissue. Am J Physiol. 263:E850-855. 1992.

25. Cassard-Doulcier AM, Gelly C, Fox N, Schrementi J, Raimbault S, Klaus S, Forest C, Bouillaud F, Ricquier D. Tissue-specific and beta-adrenergic regulation of the mitochondrial uncoupling protein gene: control by cis-acting elements in the 5'- flanking region. Mol Endocrinol. 7:497-506. 1993.

26. Kozak UC, Kopecky J, Teisinger J, Enerback S, Boyer B, Kozak LP. An upstream enhancer regulating brown-fat-specific expression of the mitochondrial uncoupling protein gene. Mol Cell Biol. 14:59-67. 1994.

27. Puigserver P, Wu Z, Park CW, Graves R, Wright M, Spiegelman BM. A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis. Cell. 92:829-839. 1998.

28. Wu Z, Puigserver P, Andersson U, Zhang C, Adelmant G, Mootha V, Troy A, Cinti S, Lowell B, Scarpulla RC, Spiegelman BM. Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1. Cell. 98:115-124. 1999.

29. Lowell BB, S-Susulic V, Hamann A, Lawitts JA, Himms-Hagen J, Boyer BB, Kozak LP, Flier JS. Development of obesity in transgenic mice after genetic ablation of brown adipose tissue. Nature. 366:740-742. 1993.

30. Lowell BB, Spiegelman BM. Towards a molecular understanding of adaptive thermogenesis. Nature. 404:652-660. 2000.