Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review
  • Published:

Adaptive thermogenesis in humans

Abstract

The increasing prevalence of obesity and its comorbidities reflects the interaction of genes that favor the storage of excess energy as fat with an environment that provides ad libitum availability of energy-dense foods and encourages an increasingly sedentary lifestyle. Although weight reduction is difficult in and of itself, anyone who has ever lost weight will confirm that it is much harder to keep the weight off once it has been lost. The over 80% recidivism rate to preweight loss levels of body fatness after otherwise successful weight loss is due to the coordinate actions of metabolic, behavioral, neuroendocrine and autonomic responses designed to maintain body energy stores (fat) at a central nervous system-defined ‘ideal’. This ‘adaptive thermogenesis’ creates the ideal situation for weight regain and is operant in both lean and obese individuals attempting to sustain reduced body weights. Much of this opposition to sustained weight loss is mediated by the adipocyte-derived hormone ‘leptin’. The multiple systems regulating energy stores and opposing the maintenance of a reduced body weight illustrate that body energy stores in general and obesity in particular are actively ‘defended’ by interlocking bioenergetic and neurobiological physiologies. Important inferences can be drawn for therapeutic strategies by recognizing obesity as a disease in which the human body actively opposes the ‘cure’ over long periods of time beyond the initial resolution of symptomatology.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Leibel R, Chua S, Rosenbaum M . Chapter 157. Obesity. In: Scriver C, Beaudet A, Sly W, Valle D (eds). The Metabolic and Molecular Bases of Inherited Disease, Vol. III, 8th edn. McGraw-Hill: New York, 2001, pp 3965–4028.

    Google Scholar 

  2. West DB, Boozer CN, Moody DL, Atkinson RL . Dietary obesity in nine inbred mouse strains. Am J Physiol 1992; 262: R1025–R1032.

    CAS  PubMed  Google Scholar 

  3. Bouchard C, Tremblay A . Genetic influences on the response of body fat and fat distribution to positive and negative energy balances in human identical twins. J Nutr 1997; 127: 943S–947S.

    CAS  PubMed  Google Scholar 

  4. Bouchard C, Tremblay A, Després JP, Nadeau A, Lupien PJ, Theriault G et al. The response to long-term overfeeding in identical twins. N Engl J Med 1990; 322: 1477–1482.

    Article  CAS  PubMed  Google Scholar 

  5. Rosenbaum M . Epidemiology of pediatric obesity. Ped Annals 2007; 36: 89–95.

    Google Scholar 

  6. Lewis C, Jacobs D, McCreath H, Kiefe C, Schreiner P, Smith D et al. Weight gain continues in the 1990s: 10-year trends in weight and overweight from the CARDIA study. Coronary artery risk development in young adults. Am J Epidemiol 2000; 151: 1172–1181.

    CAS  PubMed  Google Scholar 

  7. Moore M . Interactions between physical activity and diet in the regulation of body weight. Proc Nutr Soc 2000; 59: 193–198.

    CAS  PubMed  Google Scholar 

  8. McGuire M, Wing R, Klem M, Hill J . Behavioral strategies of individuals who have maintained long-term weight losses. Obes Res 1999; 7: 334–341.

    CAS  PubMed  Google Scholar 

  9. Wing R, Hill J . Successful weight loss maintenance. Annu Rev Nutr 2001; 21: 323–341.

    CAS  PubMed  Google Scholar 

  10. Klem M, Wing R, Lang W, McGuire M, Hill J . Does weight loss maintenance become easier over time. Obes Res 2000; 8: 438–444.

    CAS  PubMed  Google Scholar 

  11. Leibel R, Rosenbaum M, Hirsch J . Changes in energy expenditure resulting from altered body weight. N Eng J Med 1995; 332: 621–628.

    CAS  Google Scholar 

  12. Weigle D, Sande K, Iverius P, Monsen E, Brunzell J . Weight loss leads to a marked decrease in nonresting energy expenditure in ambulatory human subjects. Metabolism 1988; 37: 930–936.

    CAS  PubMed  Google Scholar 

  13. Weyer C, Walford R, Harper I, Milner M, MacCallum T, Tataranni P et al. Energy metabolism after 2 y of energy restriction: the biosphere 2 experiment. Am J Clin Nutr 2000; 72: 946–953.

    CAS  PubMed  Google Scholar 

  14. van Gemert W, Westerterp KR, Acker BA, Wagenmakers AJ, Halliday D, Greve J et al. Energy, substrate and protein metabolism in morbid obesity before, during and after massive weight loss. Int J Obes 2000; 24: 711–718.

    CAS  Google Scholar 

  15. Leibel R, Hirsch J . Diminished energy requirements in reduced-obese patients. Metabolism 1984; 33: 164–170.

    CAS  PubMed  Google Scholar 

  16. dePeuter R, Withers R, Brinkman M, Tomas F, Clark D . No differences in rates of energy expenditure between post-obese women and their matched, lean controls. Int J Obes 1992; 16: 801–808.

    CAS  Google Scholar 

  17. Amatruda J, Statt M, Welle S . Total and resting energy expenditure in obese women reduced to ideal body weight. J Clin Invest 1993; 92: 1236–1242.

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Weinsier R, Hunter G, Zuckerman P, Redden D, Darnell B, Larson D et al. Energy expenditure and free-living physical activity in black and white women: comparison and after weight loss. Am J Clin Nutr 2000; 71: 1138–1146.

    CAS  PubMed  Google Scholar 

  19. Astrup A, Gotzsche P, van de Werken K, Ranneries C, Toubro S, Raben A et al. Meta-analysis of resting metabolic rate in formerly obese subjects. Am J Clin Nutr 1999; 69: 1117–1122.

    CAS  PubMed  Google Scholar 

  20. Rosenbaum M, Vandenborne K, Goldsmith R, Simoneau J, Heymsfield S, Joanisse D et al. Effects of experimental weight perturbation on skeletal muscle work efficiency in human subjects. Am J Physiol 2003; 285: R183–R192.

    CAS  Google Scholar 

  21. Klem M, Wing R, McGuire M, Seagle H, Hill J . A descriptive study of individuals successful at long term maintenance of substantial weight loss. Am J Clin Nutr 1998; 66: 239–246.

    Google Scholar 

  22. Newcomer B, Larson-Meyer D, Hunter G, Weinsier R . Skeletal muscle metabolism in overweight and post-overweight women: an isometric exercise study using (31)P magnetic resonance spectroscopy. Int J Obes 2001; 25: 1309–1315.

    CAS  Google Scholar 

  23. Pirke K, Briicjs A, Wilckens T, Marquard R, Schweiger U . Starvation induced hyperactivity in the rat: the role of endocrine and neurotransmitter changes. Neurosci Biobehav Rev 1993; 17: 287–294.

    CAS  PubMed  Google Scholar 

  24. Freyschuss U, Melcher A . Exercise energy expenditure in extreme obewsity: influence of ergometry type and weight loss. Scand J Clin Lab Invest 1978; 38: 753–759.

    CAS  PubMed  Google Scholar 

  25. Walter G, Vandenborne K, McCully K, Leigh J . Noninvasive measurement of PCr recovery kinetics in single human muscles. Am J Physiol 1997; 268: C869–C876.

    Google Scholar 

  26. Blei M, Conley K, Kushmerick M . Separate measures of ATP utilization and recovery in human skeletal muscle. J Physiol (Lond) 1993; 465: 203–222.

    CAS  Google Scholar 

  27. Goldsmith R, Joanisse D, Gallagher D, Pavlovich K, Shamoon E, Leibel R et al. Effects of experimental weight perturbation on skeletal muscle work efficiency, fuel utilization, and biochemistry in human subjects. Am J Physiol Regul Integr Comp Physiol 2010; 298: R79–R88.

    CAS  PubMed  Google Scholar 

  28. Schwartz M, Woods S, Porte D, Seeley R, Baskin D . Central nervous system control of food intake. Nature 2000; 404: 661–670.

    Article  CAS  PubMed  Google Scholar 

  29. Wardlaw S . Clinical review 127: obesity as a neuroendocrine disease: lessons to be learned from proopiomelanocortin and melanocortin receptor mutations in mice and men. J Clin Endocrinol Metab 2001; 86: 1442–1446.

    CAS  PubMed  Google Scholar 

  30. Shimomura Y, Bray GA, Lee M . Adrenalectomy and steroid treatment in obese (ob/ob) and diabetic (db/db) mice. Horm Metab Res 1987; 19: 295–299.

    CAS  PubMed  Google Scholar 

  31. Kennedy S, Brown G, McVrey G, Garfinkel P . Pineal and adrenal function before and after refeeding in anorexia nervosa. Biol Psych 1991; 30: 216–224.

    CAS  Google Scholar 

  32. Guldstrand M, Ahren B, Wredling R, Backman L, Linus P, Adamson U . Alteration of the counterregulatory responses to insulin-induced hypoglycemia and of cognitive function after massive weight reduction in severely obese subjects. Metabolism 2003; 52: 900–907.

    CAS  PubMed  Google Scholar 

  33. Yanovski J, Yanovski S, Gold P, Chorousos G . Differences in corticotropin-releasing hormone-stimulated adrenocorticotropin and cortisol before and after weight loss. J Clin Endocrinol Metab 1997; 82: 1874–1878.

    CAS  PubMed  Google Scholar 

  34. Danforth E, Burger A . The role of thyroid hormones in the control of energy expenditure. Clin Endocrinol Metab 1984; 13: 581–596.

    CAS  PubMed  Google Scholar 

  35. al-Adsani H, Hoffer L, Silva J . Resting energy expenditure is sensitive to small dose changes in patients on chronic thyroid hormone replacement. J Clin Endocrinol Metab 1997; 82: 1118–1125.

    CAS  PubMed  Google Scholar 

  36. Rosenbaum M, Hirsch J, Murphy E, Leibel R . The effects of changes in body weight on carbohydrate metabolism, catecholamine excretion, and thyroid function. Am J Clin Nutr 2000; 71: 1421–1432.

    CAS  PubMed  Google Scholar 

  37. Goodwin G, Fairburn C, Keenan J, Cowen P . The effects of dieting and weight loss upon the stimulation ofthyrotropin (TSH) bythyrotropin-releasing hormone (TRH) and suppression of cortisol secretion by dexamethasone in men and women. J Affect Dis 1988; 14: 137–144.

    CAS  PubMed  Google Scholar 

  38. Guzzaloni G, Grugni G, Moro D, Calo G, Tonelli E, Ardizzi A et al. Thyroid-stimulating hormone and prolactin responses to thyrotropin-releasing hormone in juvenile obesity before and after hypocaloric diet. J Encodrinol Invest 1995; 18: 621–629.

    CAS  Google Scholar 

  39. Rosenbaum M, Nicolson M, Hirsch J, Murphy E, Chu F, Leibel R . Effects of weight change on plasma leptin concentrations and energy expenditure. J Clin Endocrinol Metab 1997; 82: 3647–3654.

    CAS  PubMed  Google Scholar 

  40. Fekete C, Legradi G, Mihaly E, Huang Q, Tatro J, Rand W et al. Alpha-melanocyte-stimulating hormone is contained in nerve terminals innervating thyrotropin-releasing hormone-synthesizing neurons in the hypothalamic paraventricular nucleus and prevents fasting-induced suppression of prothyrotropin-releasing hormone gene expression. J Neurosci 2000; 20: 1550–1558.

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Harris M, Aschkenasi C, Elias C, Chandrankunnel A, Nillni E, Bjorbaek C et al. Transcriptional regulation of the thyrotropin-releasing hormone gene by leptin and melanocortin signaling. J Clin Invest 2001; 107: 111–120.

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Lang C, Rayos G, Chomsky D, Wood A, Wilson J . Effect of sympathoinhibition on exercise performance in patients with heart failure. Circulation 1997; 96: 238–245.

    CAS  PubMed  Google Scholar 

  43. Aronne L, Mackintosh R, Rosenbaum M, Leibel R, Hirsch J . Autonomic nervous system activity in weight gain and weight loss. Am J Physiol 1995; 38: R222–R225.

    Google Scholar 

  44. Kardos A, Taylor D, Thompson C, Styles P, Hands L, Collin J et al. Sympathetic denervation of the upper limb improves forearm exercise performance and skeletal muscle bioenergetics. Circulation 2000; 13: 2716–2720.

    Google Scholar 

  45. Dobbins R, Szczepaniak L, Zhang W, McGarry J . Chemical sympathectomy alters regulation of body weight during prolonged ICV leptin infusion. Am J Physiol 2003; 284: E778–E787.

    CAS  Google Scholar 

  46. Aronne L, Mackintosh R, Rosenbaum M, Leibel R, Hirsch J . Cardiac autonomic nervous system activity in obese and never-obese young men. Obes Res 1997; 5: 354–359.

    Google Scholar 

  47. Kim M, Small C, Stanley S, Morgan D, Seal L, Kong W et al. The central melanocortin system affects the hypothalamo-pituitary thyroid axis and may mediate the effect of leptin. J Clin Invest 2000; 105: 1005–1011.

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Flier J, Harris M, Hollenberg A . Leptin, nutrition, and the thyroid: the why, the wherefore, and the wiring. J Clin Invest 2000; 105: 859–861.

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Cannon B, Nedergaard J . Brown adipose tissue: function and physiological significance. Physiol Rev 2004; 84: 277–359.

    CAS  PubMed  Google Scholar 

  50. Trayhurn P, Nicholls D (eds). Brown Adipose Tissue. Edward Arnold: Baltimore, MD, USA, 1986.

    Google Scholar 

  51. Leibel R, Berry E, Hirsch J . In vivo evidence for catechol-responsive brown adipose tissue in obese patients. Proceedings of the Fifth International Congress on Obesity, Jerusalem, Israel, 1987.

    Google Scholar 

  52. Chemogubova E, Hurchinson D, Nedergaard J, Bengtsson T . Alpha1- and beta1-adrenoceptor signaling fully compensates for beta3-adrenoceptor deficiency in brown adipocyte norepinephrine-stimulated glucose uptake. Endocrinology 2005; 146: 2271–2284.

    Google Scholar 

  53. Alkemade A . Central and peripheral effects of thyroid hormone signalling in the control of energy metabolism. J Neuroendocrinol 2010; 22: 56–63.

    CAS  PubMed  Google Scholar 

  54. Cypress A, Lehman S, Williams G, Tal I, Rodman D, Goldfine A et al. Identification and importance of brown adipose tissue in adult humans. N Eng J Med 2009; 360: 1509–1517.

    Google Scholar 

  55. Seale P, Lazar M . Brown fat in humans: turning up the heat on obesity. Diabetes 2009; 68: 1482–1484.

    Google Scholar 

  56. Nedergaard J, Connolly E, Cannon B . Brown adipose tissue in the mammalian neonate. In: Trayhurn P, Nicholls D (eds). Brown Adipose Tissue. Edward Arnold: Baltimore, MD, USA, 1986, pp 152–213.

    Google Scholar 

  57. Astrup A, Bulow J, Madsen J, Christensen N . Contribution of BAT and skeletal muscle to thermogenesis induced by ephedrine in man. Am J Physiol 1985; 248: E507–E515.

    CAS  PubMed  Google Scholar 

  58. Nedergard J, Bengtsson T, Cannon B . Unexpected evidence for active brown adipose tissue in adult humans. Am J Physiol 2007; 293: E444–E452.

    Google Scholar 

  59. Truong M, Erasmus J, Munden R, Marom E, Sabloff B, Gladish G et al. Focal FDG uptake in mediastinal brown fat mimicking malignancy: a potential pitfall resolved on PET/CT. Am J Roentgenol 2004; 183: 1127–1132.

    Google Scholar 

  60. Chib C, Katsuragi I, Simada T, Adachi I, Satoh Y, Noguchi H et al. Evaluation of human brown adipose tissue using positron emission tomography, computerised tomography and histochemical studies in association with body mass index, visceral fat accumulation and insulin resistance (Abstract). Obes Rev 2006; 7 (Suppl. 2): 87.

    Google Scholar 

  61. Jacobsson H, Bruzelius M, Larsson S . Reduction of FDG uptake in brown adipose tissue by propranolol. Eur J Nucl Mol Imaging 2005; 32: 1130.

    Google Scholar 

  62. Tatsumi M, Engles J, Ishimori T, Nicely O, Cohade C, Wahl R . Intense (18)F-FDG uptake in brown fat can be reduced pharmacologically. J Nucl Med 2004; 45: 1189–1193.

    CAS  PubMed  Google Scholar 

  63. Soderlund V, Larsson S, Jacobsson H . Reduction of FGD uptake in brown adipose tissue in clinical patients by a single dose of propranolol. Eur J Nucl Med Mol Imaging 2007; 45: 1018–1022.

    Google Scholar 

  64. Lichtenbelt W, Vanjommeng J, Smulders N, Drossaerts J, Kemerink G, Bouvy N et al. Cold-activated brown adipose tissue in healthy men. N Eng J Med 2009; 360: 1500–1508.

    Google Scholar 

  65. Virtanen K, Lidell M, Orava J, Jeglind M, Westergren R, Niemi T et al. Functional brown adipose tissue in healthy adults. N Eng J Med 2009; 360: 1518–1525.

    CAS  Google Scholar 

  66. Chernogubova E, Cannon B, Bengtsson T . Norepinephrine increases glucose transport in brown adipocytes via 3-adrenoceptors through a cAMP, PKA and PI3-kinase-dependent pathway stimulating conventional and novel PKCs. Endocrinol 2004; 145: 269–280.

    CAS  Google Scholar 

  67. Marette A, Bukowiecki L . Noradrenaline stimulates glucose transport in rat brown adipocytes by activating thermogenesis. Evidence that fatty acid activation of mitochondrial respiration enhances glucose transport. Biochem J 1991; 277: 119–124.

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Elobeid M, Allison D . Putative environmental-endocrine disruptors and obesity: a review. Curr Opin Endocrinol Diabetes Obes 2008; 15: 403–408.

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Schwartz M, Woods S, Seeley R, Barsh G, Baskin D, Leibel R . Is the energy homeostasis system inherently biased toward weight gain? Diabetes 2003; 52: 232–238.

    CAS  PubMed  Google Scholar 

  70. Tremblay A, Després J, Theriault G, Fournier G, Bouchard C . Overfeeding and energy expenditure in humans. Am J Clin Nutr 1992; 56: 857–862.

    CAS  PubMed  Google Scholar 

  71. Dulloo A, Girardier L . 24 hour energy expenditure several months after weight loss in the underfed rat: evidence for a chronic decrease in whole-body metabolic efficiency. Int J Obes 1993; 17: 115–123.

    CAS  Google Scholar 

  72. Rosenbaum M, Hirsch J, Gallagher D, Leibel R . Long-term persistence of adaptive thermogenesis in subjects who have maintained a reduced body weight. Am J Clin Nutr 2008; 88: 906–912.

    CAS  PubMed  Google Scholar 

  73. Rothwell N, Stock M . Energy expenditure of cafeteria-fed rats determined from measurements of energy balance and indirect calorimetry. J Physiol (Lond) 1982; 328: 371–377.

    CAS  Google Scholar 

  74. Levin BE, Triscari J, Sullivan AC . Altered sympathetic activity during development of diet-induced obesity in rat. Am J Physiol 1983; 244: R347–R355.

    CAS  PubMed  Google Scholar 

  75. Corbett SW, Stern JS, Keesey RE . Energy expenditure in rats with diet-induced obesity. Am J Clin Nutr 1986; 44: 173–180.

    CAS  PubMed  Google Scholar 

  76. Murgatroyd P, Goldberg G, Leahy F, Prentice A . Effects of inactivity and diet composition on human energy balance. Int J Obes 1999; 23: 1269–1275.

    CAS  Google Scholar 

  77. Doucet E, Cameron J . Appetite control after weight loss: what is the role of bloodborne peptides? Am J Physiol Nutr Metab 2007; 32: 523–532.

    CAS  Google Scholar 

  78. Kissileff H, Thornton M, Torres M, Pavlovich K, Leibel R, Rosenbaum M . Maintenance of reduced body weight in humans is associated with leptin-reversible declines in satiation (submitted).

  79. Rosenbaum M, Nicolson M, Hirsch J, Heymsfield S, Gallagher D, Chu F et al. Effects of gender, body composition, and menopause on plasma concentrations of leptin. J Clin Endocrinol Metab 1996; 81: 3424–3427.

    CAS  PubMed  Google Scholar 

  80. Leibel R . The role of leptin in the control of body weight. Nutr Rev 2002; 60: S15–S19.

    PubMed  Google Scholar 

  81. Heini A, Lara-Castro C, Kirk K, Considine R, Caro J, Weinsier R . Association of leptin and hunger-satiety ratings in obese women. Int J Obes 1998; 22: 1084–1087.

    CAS  Google Scholar 

  82. Farooqi I, Jebb S, Langmack G, Lawrence E, Cheetham C, Prentice A et al. Effects of recombinant leptin therapy in a child with congenital leptin deficiency. N Eng J Med 1999; 341: 879–884.

    CAS  Google Scholar 

  83. Campfield LA, Smith FJ, Guisez Y, Devos R, Burn P . Recombinant mouse OB protein: evidence for a peripheral signal linking adiposity and central neural networks. Science 1995; 269: 546–549.

    CAS  PubMed  Google Scholar 

  84. Boozer C, Love R, Cha M, Leibel R, Aronne L . Synergy of leptin and sibutramine in treatment of diet-induced obesity in rats. Metabolism 2001; 50: 889–893.

    CAS  PubMed  Google Scholar 

  85. Korner J, Chua S, Williams J, Leibel R, Wardlaw S . Regulation of hypothalamic pro-opiomalanocortin by lean and obese rats. Neuroendocrinol 1999; 70: 377–383.

    CAS  Google Scholar 

  86. Ollmann M, Wilson B, Yang Y, Kerns J, Chen Y, Barsh G . Antagonism of central melanocortin receptors in vitro and in vivo by agouti-related protein. Science 1997; 278: 135–138.

    CAS  PubMed  Google Scholar 

  87. Farooqi I, Keogh J, Yeo G, Lank E, Ceetham T, O’Rahilly S . Clinical spectrum of obesity and mutations in the melanocortin 4 receptor gene. N Eng J Med 2003; 348: 1085–1095.

    CAS  Google Scholar 

  88. Krude H, Biebermann H, Luck W, Horn R, Brabant G, Gruters A . Severe early-onset obesity, adrenal insufficiency, and red hair pigmentation caused by POMC nutations in humans. Nat Genet 1998; 19: 155–157.

    CAS  PubMed  Google Scholar 

  89. Yaswen L, Diehl N, Brennan M, Hochgeswender U . Obesity in the mouse model of pro-opiomelanocortin deficiency responds to peripheral melanocortin. Nat Med 1999; 5: 1066–1070.

    CAS  PubMed  Google Scholar 

  90. Naggert JK, Fricker LD, Varlamov O, Nishin RM, Rouille T, Steiner DF et al. Hyperproinsulinaemia in obese fat/fat mice associated with a carboxypeptidase E mutation which reduces enzyme activity. Nature Genet 1995; 10: 135–142.

    CAS  PubMed  Google Scholar 

  91. Jackson RS, Creemers JWM, Ohagi S, Raffin-Sanson M-L, Sanders L, Montague CT et al. Obesity and impaired prohormone processing associated with mutations in the human prohormone convertase 1 gene. Nat Genet 1997; 16: 303.

    CAS  PubMed  Google Scholar 

  92. Korner J, Wardlaw S, Liu S, Conwell I, Leibel R, Chua S . Effects of leptin receptor mutation on Agrp gene expression in fed and fasted lean and obese (LA/N-faf) rats. Endocrinol 2000; 141: 2465–2471.

    CAS  Google Scholar 

  93. Solinas G, Summermatter S, Mainieri D, Gubler M, Pirola L, Wymann M et al. The direct effect of leptin on skeletal muscle thermogenesis is mediated by substrate cycling between de novo lipogenesis and lipid oxidation. FEBS Lett 2004; 577: 539–544.

    CAS  PubMed  Google Scholar 

  94. Satoh N, Ogawa Y, Katsuura G, Numata Y, Tsuji T, Hayase M et al. Sympathetic activation of leptin via the ventromedial hypothalamus: leptin-induced increase in catecholamine secretion. Diabetes 1999; 48: 1787–1793.

    CAS  PubMed  Google Scholar 

  95. Heymsfield SB, Greenberg AS, Fujioka K, Dixon RM, Kushner R, Hunt T et al. Recombinant leptin for weight loss in obese and lean adults: a randomized, controlled, dose-escalation trial. JAMA 1999; 292: 1568–1575.

    Google Scholar 

  96. Campfield L, Smith F, Guisez Y, Devos R, Burn P . Recombinant mouse OB protein: evidence for a peripheral signal linking adiposity and central neural networks. Science 1995; 269: 546–548.

    CAS  PubMed  Google Scholar 

  97. Rosenbaum M, Goldsmith R, Bloomfield D, Magnano A, Weimer L, Heymsfield S et al. Low dose leptin reverses skeletal muscle, autonomic, and neuroendocrine adaptations to maintenance of reduced weight. J Clin Invest 2005; 115: 3579–3586.

    CAS  PubMed  PubMed Central  Google Scholar 

  98. Ravussin E, Smith S, Mitchell J, Shringarpure R, Shan K, Maier H et al. Enhanced weight loss with pramlintide/metreleptin: an integrated neurohormonal approach to obesity pharmacotherapy. Obesity 2009; 17: 1736–1743.

    CAS  PubMed  Google Scholar 

  99. Welt C, Chan J, Bullen J, Murphy R, Smith P, DePaoli A et al. Recombinant human leptin in women with hypothalamic amenorrhea. N Eng J Med 2004; 351: 987–997.

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to M Rosenbaum.

Ethics declarations

Competing interests

M Rosenbaum has received consulting fees from Florida Children's Hospital. RL Leibel declared no financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rosenbaum, M., Leibel, R. Adaptive thermogenesis in humans. Int J Obes 34 (Suppl 1), S47–S55 (2010). https://doi.org/10.1038/ijo.2010.184

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ijo.2010.184

Keywords

This article is cited by

Search

Quick links