Leptin and its emerging role in children and adolescents

Clinical Pediatric Endocrinology

Volumn 15, Issue 1, 2006, Pages 1-14

  Kelesidis, Iosif ^a   Mantzoros, Christos S ^a,b  

^a HARVARD MEDICAL SCHOOL   (United States)

^b BETH ISRAEL DEACONESS MEDICAL CENTER   (United States)

Author keywords

Adipocytokines; Hypothalamic amenorrhea; Insulin resistance; Leptin; Obesity; Physiology

Indexed keywords

GONADORELIN; LEPTIN;

ADIPOCYTE; ADOLESCENT; AMENORRHEA; ANOREXIA NERVOSA; BLOOD PRESSURE REGULATION; BONE DENSITY; CHILD; EATING DISORDER; GENE MUTATION; HEMATOPOIESIS; HIGHLY ACTIVE ANTIRETROVIRAL THERAPY; HOMEOSTASIS; HORMONE ACTION; HORMONE DEFICIENCY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; HYPERLIPIDEMIA; HYPOTHALAMUS DISEASE; HYPOTHALAMUS HYPOPHYSIS THYROID SYSTEM; IMMUNE RESPONSE; INSULIN RESISTANCE; LIPODYSTROPHY; METABOLIC SYNDROME X; NEUROENDOCRINE SYSTEM; OBESITY; OSTEOLYSIS; PUBERTY; REVIEW; WEIGHT REDUCTION;

EID: 33644545453     PISSN: 09185739     EISSN: None     Source Type: Journal    
DOI: 10.1297/cpe.15.1     Document Type: Review

References (137)

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 1994;372:425-32.
2. Considine RV, Sinha MK, Heiman ML, Kriauciunas A, Stephens TW, Nyce MR, et al. Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med 1996;334:292-5.
3. Moran O, Phillip M. Leptin: obesity, diabetes and other peripheral effects - a review. Pediatr Diabetes 2003;4:101-9.
4. Mantzoros CS. The role of leptin in human obesity and disease: a review of current evidence. Ann Intern Med 1999;130:671-80.
5. Boden G, Chen X, Mozzoli M, Ryan I. Effect of fasting on serum leptin in normal human subjects. J Clin Endocrinol Metab 1996;81:3419-23.
6. Kolaczynski JW, Nyce MR, Considine RV, Boden G, Nolan JJ, Henry R, et al. Acute and chronic effects of insulin on leptin production in humans: studies in vivo and in vitro. Diabetes 1996;45:699-701.
7. Licinio J, Mantzoros C, Negrao AB, Cizza G, Wong ML, Bongiorno PB, et al. Human leptin levels are pulsatile and inversely related to pituitary-adrenal function. Nat Med 1997;3:575-9.
8. Mantzoros CS, Moschos SJ. Leptin: in search of role(s) in human physiology and pathophysiology. Clin Endocrinol (Oxf) 1998;49:551-67.
9. Lee GH, Proenca R, Montez JM, Carroll KM, Darvishzadeh JG, Lee JI, et al. Abnormal splicing of the leptin receptor in diabetic mice. Nature 1996;379:632-5.
10. Tartaglia LA. The leptin receptor. J Biol Chem 1997;272:6093-6.
11. Mantzoros CS. Leptin and the hypothalamus: neuroendocrine regulation of food intake. Mol Psychiatry 1999;4:8-7.
12. Auwerx J, Staels B. Leptin. Lancet 1998;351:737-42.
13. Sinha MK, Opentanova I, Ohannesian JP, Kolaczynski JW, Heiman ML, Hale J, 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;98:1277-82.
14. Kitawaki J, Koshiba H, Ishihara H, Kusuki I, Tsukamoto K, Honjo H. Expression of leptin receptor in human endometrium and fluctuation during the menstrual cycle. J Clin Endocrinol Metab 2000;85:1946-50.
15. Elmquist JK, Ahima RS, Elias CF, Flier JS, Saper CB. Leptin activates distinct projections from the dorsomedial and ventromedial hypothalamic nuclei. Proc Natl Acad Sci U S A 1998;95:741-6.
16. Woods AJ, Stock MJ. Leptin activation in hypothalamus. Nature 1996;381:745.
17. Bates SH, Stearns WH, Dundon TA, Schubert M, Tso AW, Wang Y, et al. STAT3 signalling is required for leptin regulation of energy balance but not reproduction. Nature 2003;421:856-9.
18. Niswender KD, Morton GJ, Stearns WH, Rhodes CJ, Myers MG Jr, Schwartz MW. Intracellular signalling: key enzyme in leptin-induced anorexia. Nature 2001;413:794-5.
19. Hegyi K, Fulop K, Kovacs K, Toth S, Falus A. Leptin-induced signal transduction pathways. Cell Biol Int 2004;28:159-69.
20. Elchebly M, Payette P, Michaliszyn E, Cromlish W, Collins S, Loy AL, et al. Increased insulin sensitivity and obesity resistance in mice lacking the protein tyrosine phosphatase-1B gene. Science 1999;283:1544-8.
21. Howard JK, Cave BJ, Oksanen LJ, Tzameli I, Bjorbaek C, Flier JS. Enhanced leptin sensitivity and attenuation of diet-induced obesity in mice with haploinsufficiency of Socs3. Nat Med 2004;10:734-8.
22. Cowley MA, Smart JL, Rubinstein M, Cerdan MG, Diano S, Horvath TL, et al. Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus. Nature 2001;411:480-4.
23. Farooqi IS, Keogh JM, Yeo GS, Lank EJ, Cheetham T, O'Rahilly S. Clinical spectrum of obesity and mutations in the melanocortin 4 receptor gene. N Engl J Med 2003;348:1085-95.
24. Sahu A. Minireview: a hypothalamic role in energy balance with special emphasis on leptin. Endocrinology 2004;145:2613-20.
25. Baker M, Gaukrodger N, Mayosi BM, Imrie H, Farrall M, Watkins H, et al. Association between common polymorphisms of the proopiomelanocortin gene and body fat distribution: a family study. Diabetes 2005;54:2492-6.
26. Pinto S, Roseberry AG, Liu H, Diano S, Shanabrough M, Cai X, et al. Rapid rewiring of arcuate nucleus feeding circuits by leptin. Science 2004;304:110-5.
27. Bouret SG, Draper SJ, Simerly RB. Trophic action of leptin on hypothalamic neurons that regulate feeding. Science 2004;304:108-10.
28. Matochik JA, London ED, Yildiz BO, Ozata M, Caglayan S, DePaoli AM, et al. Effect of leptin replacement on brain structure in genetically leptin-deficient adults. J Clin Endocrinol Metab 2005;90:2851-4.
29. Moschos S, Chan JL, Mantzoros CS. Leptin and reproduction: a review. Fertil Steril 2002;77:433-44.
30. Jin L, Zhang S, Burguera BG, Couce ME, Osamura RY, Kulig E, et al. Leptin and leptin receptor expression in rat and mouse pituitary cells. Endocrinology 2000;141:333-9.
31. Karlsson C, Lindell K, Svensson E, Bergh C, Lind P, Billig H, et al. Expression of functional leptin receptors in the human ovary. J Clin Endocrinol Metab 1997;82:4144-8.
32. Lebrethon MC, Vandersmissen E, Gerard A, Parent AS, Junien JL, Bourguignon JP. In vitro stimulation of the prepubertal rat gonadotropin- releasing hormone pulse generator by leptin and neuropeptide Y through distinct mechanisms. Endocrinology 2000;141:1464-9.
33. Magni P, Vettor R, Pagano C, Calcagno A, Beretta E, Messi E, et al. Expression of a leptin receptor in immortalized gonadotropin-releasing hormone-secreting neurons. Endocrinology 1999;140:1581-5.
34. Chehab FF, Lim ME, Lu R. Correction of the sterility defect in homozygous obese female mice by treatment with the human recombinant leptin. Nat Genet 1996;12:318-20.
35. Mounzih K, Lu R, Chehab FF. Leptin treatment rescues the sterility of genetically obese ob/ob males. Endocrinology 1997;138:1190-3.
36. Ahima RS, Prabakaran D, Mantzoros C, Qu D, Lowell B, Maratos-Flier E, et al. Role of leptin in the neuroendocrine response to fasting. Nature 1996;382:250-2.
37. Montague CT, Farooqi IS, Whitehead JP, Soos MA, Rau H, Wareham NJ, et al. Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature 1997;387:903-8.
38. Strobel A, Issad T, Camoin L, Ozata M, Strosberg AD. A leptin missense mutation associated with hypogonadism and morbid obesity. Nat Genet 1998;18:213-5.
39. Ozata M, Ozdemir IC, Licinio J. Human leptin deficiency caused by a missense mutation: multiple endocrine defects, decreased sympathetic tone, and immune system dysfunction indicate new targets for leptin action, greater central than peripheral resistance to the effects of leptin, and spontaneous correction of leptin-mediated defects. J Clin Endocrinol Metab 1999;84:3686-95.
40. Clement K, Vaisse C, Lahlou N, Cabrol S, Pelloux V, Cassuto D, et al. A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction. Nature 1998;392:398-401.
41. Farooqi IS, Jebb SA, Langmack G, Lawrence E, Cheetham CH, Prentice AM, et al. Effects of recombinant leptin therapy in a child with congenital leptin deficiency. N Engl J Med 1999;341:879-84.
42. Farooqi IS, Matarese G, Lord GM, Keogh JM, Lawrence E, Agwu C, et al. Beneficial effects of leptin on obesity, T cell hyporesponsiveness, and neuroendocrine/metabolic dysfunction of human congenital leptin deficiency. J Clin Invest 2002;110:1093-103.
43. Licinio J, Caglayan S, Ozata M, Yildiz BO, De Miranda PB, O'Kirwan F, et al. Phenotypic effects of leptin replacement on morbid obesity, diabetes mellitus, hypogonadism, and behavior in leptin-deficient adults. Proc Natl Acad Sci U S A 2004.
44. Licinio J, Negrao AB, Mantzoros C, Kaklamani V, Wong ML, Bongiorno PB, et al. Synchronicity of frequently sampled, 24-h concentrations of circulating leptin, luteinizing hormone, and estradiol in healthy women. Proc Natl Acad Sci U S A 1998;95:2541-6.
45. Chan JL, Heist K, DePaoli AM, Veldhuis JD, Mantzoros CS. The role of falling leptin levels in the neuroendocrine and metabolic adaptation to short-term starvation in healthy men. J Clin Invest 2003;111:1409-21.
46. Heiman ML, Ahima RS, Craft LS, Schoner B, Stephens TW, Flier JS. Leptin inhibition of the hypothalamic-pituitary-adrenal axis in response to stress. Endocrinology 1997;138:3859-63.
47. Korbonits M, Chitnis MM, Gueorguiev M, Norman D, Rosenfelder N, Suliman M, et al. The release of leptin and its effect on hormone release from human pituitary adenomas. Clin Endocrinol (Oxf) 2001;54:781-9.
48. Giusti M, Bocca L, Florio T, Corsaro A, Spaziante R, Schettini G, et al. In vitro effect of human recombinant leptin and expression of leptin receptors on growth hormone-secreting human pituitary adenomas. Clin Endocrinol (Oxf) 2002;57:449-55.
49. Chen C, Roh SG, Nie GY, Loneragan K, Xu RW, Ruan M, et al. The in vitro effect of leptin on growth hormone secretion from primary cultured ovine somatotrophs. Endocrine 2001;14:73-8.
50. Kim MS, Small CJ, Stanley SA, Morgan DG, Seal LJ, Kong WM, et al. The central melanocortin system affects the hypothalamo-pituitary thyroid axis and may mediate the effect of leptin. J Clin Invest 2000;105:1005-11.
51. Legradi G, Emerson CH, Ahima RS, Flier JS, Lechan RM. Leptin prevents fasting-induced suppression of prothyrotropin-releasing hormone messenger ribonucleic acid in neurons of the hypothalamic paraventricular nucleus. Endocrinology 1997;138:2569-76.
52. Seoane LM, Carro E, Tovar S, Casanueva FF, Dieguez C. Regulation of in vivo TSH secretion by leptin. Regul Pept 2000;92:25-9.
53. Rosenbaum M, Murphy EM, Heymsfield SB, Matthews DE, Leibel RL. Low dose leptin administration reverses effects of sustained weight-reduction on energy expenditure and circulating concentrations of thyroid hormones. J Clin Endocrinol Metab 2002;87:2391-4.
54. Mantzoros CS, Ozata M, Negrao AB, Suchard MA, Ziotopoulou M, Caglayan S, et al. Synchronicity of frequently sampled thyrotropin (TSH) and leptin concentrations in healthy adults and leptin-deficient subjects: evidence for possible partial TSH regulation by leptin in humans. J Clin Endocrinol Metab 2001;86:3284-91.
55. Thomas T, Gori F, Khosla S, Jensen MD, Burguera B, Riggs BL. Leptin acts on human marrow stromal cells to enhance differentiation to osteoblasts and to inhibit differentiation to adipocytes. Endocrinology 1999;140:1630-8.
56. Maor G, Rochwerger M, Segev Y, Phillip M. Leptin acts as a growth factor on the chondrocytes of skeletal growth centers. J Bone Miner Res 2002;17:1034-43.
57. Cornish J, Callon KE, Bava U, Lin C, Naot D, Hill BL, et al. Leptin directly regulates bone cell function in vitro and reduces bone fragility in vivo. J Endocrinol 2002;175:405-15.
58. Gordeladze JO, Drevon CA, Syversen U, Reseland JE. Leptin stimulates human osteoblastic cell proliferation, de novo collagen synthesis, and mineralization: impact on differentiation markers, apoptosis, and osteoclastic signaling. J Cell Biochem 2002;85:825-36.
59. Steppan CM, Crawford DT, Chidsey-Frink KL, Ke H, Swick AG. Leptin is a potent stimulator of bone growth in ob/ob mice. Regul Pept 2000;92:73-8.
60. Burguera B, Hofbauer LC, Thomas T, Gori F, Evans GL, Khosla S, et al. Leptin reduces ovariectomy-induced bone loss in rats. Endocrinology 2001;142:3546-53.
61. Ducy P, Amling M, Takeda S, Priemel M, Schilling AF, Beil FT, et al. Leptin inhibits bone formation through a hypothalamic relay: a central control of bone mass. Cell 2000;100:197-207.
62. Elefteriou F, Takeda S, Ebihara K, Magre J, Patano N, Kim CA, et al. Serum leptin level is a regulator of bone mass. Proc Natl Acad Sci U S A 2004;101:3258-63.
63. Thomas T, Burguera B, Melton LJ III, Atkinson EJ, O'Fallon WM, Riggs BL, et al. Role of serum leptin, insulin, and estrogen levels as potential mediators of the relationship between fat mass and bone mineral density in men versus women. Bone 2001;29:114-20.
64. Yamauchi M, Sugimoto T, Yamaguchi T, Nakaoka D, Kanzawa M, Yano S, et al. Plasma leptin concentrations are associated with bone mineral density and the presence of vertebral fractures in postmenopausal women. Clin Endocrinol (Oxf) 2001;55:341-7.
65. Pasco JA, Henry MJ, Kotowicz MA, Collier GR, Ball MJ, Ugoni AM, et al. Serum leptin levels are associated with bone mass in nonobese women. J Clin Endocrinol Metab 2001;86:1884-7.
66. Blain H, Vuillemin A, Guillemin F, Durant R, Hanesse B, de Talance N, et al. Serum leptin level is a predictor of bone mineral density in postmenopausal women. J Clin Endocrinol Metab 2002;87:1030-5.
67. Goulding A, Taylor RW. Plasma leptin values in relation to bone mass and density and to dynamic biochemical markers of bone resorption and formation in postmenopausal women. Calcif Tissue Int 1998;63:456-8.
68. Rauch F, Blum WF, Klein K, Allolio B, Schonau E. Does leptin have an effect on bone in adult women? Calcif Tissue Int 1998;63:453-5.
69. Odabasi E, Ozata M, Turan M, Bingol N, Yonem A, Cakir B, et al. Plasma leptin concentrations in postmenopausal women with osteoporosis. Eur J Endocrinol 2000;142:170-3.
70. Ruhl CE, Everhart JE. Relationship of serum leptin concentration with bone mineral density in the United States population. J Bone Miner Res 2002;17:1896-903.
71. Roemmich JN, Clark PA, Mantzoros CS, Gurgol CM, Weltman A, Rogol AD. Relationship of leptin to bone mineralization in children and adolescents. J Clin Endocrinol Metab 2003;88:599-604.
72. Simha V, Zerwekh JE, Sakhaee K, Garg A. Effect of subcutaneous leptin replacement therapy on bone metabolism in patients with generalized lipodystrophy. J Clin Endocrinol Metab 2002;87:4942-5.
73. Iwamoto I, Douchi T, Kosha S, Murakami M, Fujino T, Nagata Y. Relationships between serum leptin level and regional bone mineral density, bone metabolic markers in healthy women. Acta Obstet Gynecol Scand 2000;79:1060-4.
74. Sato M, Takeda N, Sarui H, Takami R, Takami K, Hayashi M, et al. Association between serum leptin concentrations and bone mineral density, and biochemical markers of bone turnover in adult men. J Clin Endocrinol Metab 2001;86:5273-6.
75. Blum M, Harris SS, Must A, Naumova EN, Phillips SM, Rand WM, et al. Leptin, body composition and bone mineral density in premenopausal women. Calcif Tissue Int 2003;73:27-32.
76. Martini G, Valenti R, Giovani S, Franci B, Campagna S, Nuti R. Influence of insulin-like growth factor-1 and leptin on bone mass in healthy postmenopausal women. Bone 2001;28:113-7.
77. Coen G. Leptin and bone metabolism. J Nephrol 2004;17:187-9.
78. Haynes WG, Sivitz WI, Morgan DA, Walsh SA, Mark AL. Sympathetic and cardiorenal actions of leptin. Hypertension 1997;30:619-23.
79. Dunbar JC, Hu Y, Lu H. Intracerebroventricular leptin increases lumbar and renal sympathetic nerve activity and blood pressure in normal rats. Diabetes 1997;46:2040-3.
80. Haynes WG. Role of leptin in obesity-related hypertension. Exp Physiol 2005.
81. Jackson EK, Li P. Human leptin has natriuretic activity in the rat. Am J Physiol 1997;272:F333-8.
82. Shek EW, Brands MW, Hall JE. Chronic leptin infusion increases arterial pressure. Hypertension 1998;31:409-14.
83. Rahmouni K, Morgan DA, Morgan GM, Mark AL, Haynes WG. Role of selective leptin resistance in diet-induced obesity hypertension. Diabetes 2005;54:2012-8.
84. Rahmouni K, Haynes WG. Leptin and the cardiovascular system. Recent Prog Horm Res 2004;59:225-44.
85. Lord GM, Matarese G, Howard JK, Lechler RI. The bioenergetics of the immune system. Science 2001;292:855-6.
86. Chandra RK. Cell-mediated immunity in genetically obese C57BL/6J ob/ob) mice. Am J Clin Nutr 1980;33:13-6.
87. Howard JK, Lord GM, Matarese G, Vendetti S, Ghatei MA, Ritter MA, et al. Leptin protects mice from starvation-induced lymphoid atrophy and increases thymic cellularity in ob/ob mice. J Clin Invest 1999;104:1051-9.
88. Palacio A, Lopez M, Perez-Bravo F, Monkeberg F, Schlesinger L. Leptin levels are associated with immune response in malnourished infants. J Clin Endocrinol Metab 2002;87:3040-6.
89. Lord GM, Matarese G, Howard JK, Baker RJ, Bloom SR, Lechler RI. Leptin modulates the T-cell immune response and reverses starvation-induced immunosuppression. Nature. 1998;394:897-901.
90. Mattioli B, Straface E, Quaranta MG, Giordani L, Viora M. Leptin promotes differentiation and survival of human dendritic cells and licenses them for Th1 priming. J Immunol 2005;174:6820-8.
91. Martin-Romero C, Santos-Alvarez J, Goberna R, Sanchez-Margalet V. Human leptin enhances activation and proliferation of human circulating T lymphocytes. Cell Immunol 2000;199:15-24.
92. Santos-Alvarez J, Goberna R, Sanchez-Margalet V. Human leptin stimulates proliferation and activation of human circulating monocytes. Cell Immunol 1999;194:6-11.
93. Lord GM, Matarese G, Howard JK, Bloom SR, Lechler RI. Leptin inhibits the anti-CD3-driven proliferation of peripheral blood T cells but enhances the production of proinflammatory cytokines. J Leukoc Biol 2002;72:330-8.
94. Chan JL, Moschos SJ, Bullen J, Heist K, Li X, Kim YB, et al. Recombinant methionyl human leptin administration activates signal transducer and activator of transcription 3 signaling in peripheral blood mononuclear cells in vivo and regulates soluble tumor necrosis factor-α receptor levels in humans with relative leptin deficiency. J Clin Endocrinol Metab 2005;90:1625-31.
95. Matarese G, Moschos S, Mantzoros CS. Leptin in immunology. J Immunol 2005;174:3137-42.
96. Konopleva M, Mikhail A, Estrov Z, Zhao S, Harris D, Sanchez-Williams G, et al. Expression and function of leptin receptor isoforms in myeloid leukemia and myelodysplastic syndromes: proliferative and anti-apoptotic activities. Blood 1999;93:1668-76.
97. Gainsford T, Willson TA, Metcalf D, Handman E, McFarlane C, Ng A, et al. Leptin can induce proliferation, differentiation, and functional activation of hemopoietic cells. Proc Natl Acad Sci U S A 1996;93:14564-8.
98. Umemoto Y, Tsuji K, Yang FC, Ebihara Y, Kaneko A, Furukawa S, et al. Leptin stimulates the proliferation of murine myelocytic and primitive hematopoietic progenitor cells. Blood 1997;90:3438-43.
99. Bennett BD, Solar GP, Yuan JQ, Mathias J, Thomas GR, Matthews W. A role for leptin and its cognate receptor in hematopoiesis. Curr Biol 1996;6:1170-80.
100. Fantuzzi G, Faggioni R. Leptin in the regulation of immunity, inflammation, and hematopoiesis. J Leukoc Biol 2000;68:437-46.
101. Munzberg H, Myers MG Jr. Molecular and anatomical determinants of central leptin resistance. Nat Neurosci 2005;8:566-70.
102. Bjorbaek C, Elmquist JK, Frantz JD, Shoelson SE, Flier JS. Identification of SOCS-3 as a potential mediator of central leptin resistance. Mol Cell 1998;1:619-25.
103. Farooqi IS, Keogh JM, Kamath S, Jones S, Gibson WT, Trussell R, et al. Partial leptin deficiency and human adiposity. Nature 2001;414:34-5.
104. Mantzoros C, Flier JS, Lesem MD, Brewerton TD, Jimerson DC. Cerebrospinal fluid leptin in anorexia nervosa: correlation with nutritional status and potential role in resistance to weight gain. J Clin Endocrinol Metab 1997;82:1845-51.
105. Monteleone P, Fabrazzo M, Tortorella A, Fuschino A, Maj M. Opposite modifications in circulating leptin and soluble leptin receptor across the eating disorder spectrum. Mol Psychiatry 2002;7:641-6.
106. Krizova J, Papezova H, Haluzikova D, Parizkova J, Jiskra J, Kotrlikova E, et al. Soluble leptin receptor levels in patients with anorexia nervosa. Endocr Res 2002;28:199-205.
107. Misra M, Miller KK, Almazan C, Ramaswamy K, Aggarwal A, Herzog DB, et al. Hormonal and body composition predictors of soluble leptin receptor, leptin, and free leptin index in adolescent girls with anorexia nervosa and controls and relation to insulin sensitivity. J Clin Endocrinol Metab 2004;89:3486-95.
108. Kratzsch J, Lammert A, Bottner A, Seidel B, Mueller G, Thiery J, et al. Circulating soluble leptin receptor and free leptin index during childhood, puberty, and adolescence. J Clin Endocrinol Metab 2002;87:4587-94.
109. Welt CK, Chan JL, Bullen J, Murphy R, Smith P, DePaoli AM, et al. Recombinant human leptin in women with hypothalamic amenorrhea. N Engl J Med 2004;351:987-97.
110. Audi L, Mantzoros CS, Vidal-Puig A, Vargas D, Gussinye M, Carrascosa A. Leptin in relation to resumption of menses in women with anorexia nervosa. Mol Psychiatry 1998;3:544-7.
111. Ballauff A, Ziegler A, Emons G, Sturm G, Blum WF, Remschmidt H, et al. Serum leptin and gonadotropin levels in patients with anorexia nervosa during weight gain. Mol Psychiatry 1999;4:71-5.
112. Shimomura I, Hammer RE, Ikemoto S, Brown MS, Goldstein JL. Leptin reverses insulin resistance and diabetes mellitus in mice with congenital lipodystrophy. Nature 1999;401:73-6.
113. Sivitz WI, Walsh SA, Morgan DA, Thomas MJ, Haynes WG. Effects of leptin on insulin sensitivity in normal rats. Endocrinology 1997;138:3395-401.
114. Oral EA, Simha V, Ruiz E, Andewelt A, Premkumar A, Snell P, et al. Leptin-replacement therapy for lipodystrophy. N Engl J Med 2002;346:570-8.
115. Petersen KF, Oral EA, Dufour S, Befroy D, Ariyan C, Yu C, et al. Leptin reverses insulin resistance and hepatic steatosis in patients with severe lipodystrophy. J Clin Invest 2002;109:1345-50.
116. Cochran E, Young JR, Sebring N, DePaoli A, Oral EA, Gorden P. Efficacy of recombinant methionyl human leptin therapy for the extreme insulin resistance of the Rabson-Mendenhall syndrome. J Clin Endocrinol Metab 2004;89:1548-54.
117. Javor ED, Ghany MG, Cochran EK, Oral EA, DePaoli AM, Premkumar A, et al. Leptin reverses nonalcoholic steatohepatitis in patients with severe lipodystrophy. Hepatology 2005;41:753-60.
118. Lee JH, Chan JL, Sourlas E, Raptopoulos V, Mantzoros CS. r-metHuLeptin in replacement dose improves insulin resistance and metabolic profile in the highly active antiretroviral therapy (HAART)-induced HIV lipoatrophy and metabolic syndrome. J Clin Endocrinol Metab (In press).
119. Shalitin S, Phillip M. Role of obesity and leptin in the pubertal process and pubertal growth - a review. Int J Obes Relat Metab Disord 2003;27:869-74.
120. Mantzoros CS, Varvarigou A, Kaklamani VG, Beratis NG, Flier JS. Effect of birth weight and maternal smoking on cord blood leptin concentrations of full-term and preterm newborns. J Clin Endocrinol Metab 1997;82:2856-61.
121. Matsuda J, Yokota I, Iida M, Murakami T, Naito E, Ito M, et al. Serum leptin concentration in cord blood: relationship to birth weight and gender. J Clin Endocrinol Metab 1997;82:1642-4.
122. Sivan E, Lin WM, Homko CJ, Reece EA, Boden G. Leptin is present in human cord blood. Diabetes 1997;46:917-9.
123. Schubring C, Kiess W, Englaro P, Rascher W, Dotsch J, Hanitsch S, et al. Levels of leptin in maternal serum, amniotic fluid, and arterial and venous cord blood: relation to neonatal and placental weight. J Clin Endocrinol Metab 1997;82:1480-3.
124. Masuzaki H, Ogawa Y, Sagawa N, Hosoda K, Matsumoto T, Mise H, et al. Nonadipose tissue production of leptin: leptin as a novel placenta-derived hormone in humans. Nat Med 1997;3:1029-33.
125. McMillen IC, Muhlhausler BS, Duffield JA, Yuen BS. Prenatal programming of postnatal obesity: fetal nutrition and the regulation of leptin synthesis and secretion before birth. Proc Nutr Soc 2004;63:405-12.
126. Carro E, Senaris R, Considine RV, Casanueva FF, Dieguez C. Regulation of in vivo growth hormone secretion by leptin. Endocrinology 1997;138:2203-6.
127. Casabiell X, Pineiro V, Tome MA, Peino R, Dieguez C, Casanueva FF. Presence of leptin in colostrum and/or breast milk from lactating mothers: a potential role in the regulation of neonatal food intake. J Clin Endocrinol Metab 1997;82:4270-3.
128. Dundar NO, Anal O, Dundar B, Ozkan H, Caliskan S, Buyukgebiz A. Longitudinal investigation of the relationship between breast milk leptin levels and growth in breast-fed infants. J Pediatr Endocrinol Metab 2005;18:181-7.
129. Dyer CJ, Simmons JM, Matteri RL, Keisler DH. Leptin receptor mRNA is expressed in ewe anterior pituitary and adipose tissues and is differentially expressed in hypothalamic regions of well-fed and feed-restricted ewes. Domest Anim Endocrinol 1997;14:119-28.
130. Hassink SG, Sheslow DV, de Lancey E, Opentanova I, Considine RV, Caro JF. Serum leptin in children with obesity: relationship to gender and development. Pediatrics 1996;98:201-3.
131. Garcia-Mayor RV, Andrade MA, Rios M, Lage M, Dieguez C, Casanueva FF. Serum leptin levels in normal children: relationship to age, gender, body mass index, pituitary-gonadal hormones, and pubertal stage. J Clin Endocrinol Metab 1997;82:2849-55.
132. Mantzoros CS, Flier JS, Rogol AD. A longitudinal assessment of hormonal and physical alterations during normal puberty in boys. V. Rising leptin levels may signal the onset of puberty. J Clin Endocrinol Metab 1997;82:1066-70.
133. Rogol AD. Leptin and puberty. J Clin Endocrinol Metab 1998;83:1089-90.
134. Chan JL, Mantzoros CS. Role of leptin in energy-deprivation states: normal human physiology and clinical implications for hypothalamic amenorrhoea and anorexia nervosa. Lancet 2005;366:74-85.
135. Musso C, Cochran E, Javor E, Young J, DePaoli AM, Gorden P. The long-term effect of recombinant methionyl human leptin therapy on hyperandrogenism and menstrual function in female and pituitary function in male and female hypoleptinemic lipodystrophic patients. Metabolism 2005;54:255-63.
136. Gurkan F, Atamer Y, Ece A, Kocyigit Y, Tuzun H, Mete N. Serum leptin levels in asthmatic children treated with an inhaled corticosteroid. Ann Allergy Asthma Immunol 2004;93:277-80.
137. Ahme ML, Ong KK, Thomson AH, Dunger DB. Reduced gains in fat and fat-free mass, and elevated leptin levels in children and adolescents with cystic fibrosis. Acta Paediatr 2004;93:1185-91.