Leptin: A hormone linking activation of neuroendocrine axes with neuropathology

Psychoneuroendocrinology

Volumn 51, Issue , 2015, Pages 47-57

  Stieg, Mareike R ^a   Sievers, Caroline ^a   Farr, Olivia ^b,c   Stalla, Günter K ^a   Mantzoros, Christos S ^b,c,d  

^a MAX PLANCK INSTITUTE OF PSYCHIATRY   (Germany)

^b HARVARD MEDICAL SCHOOL   (United States)

^c VETERANS AFFAIRS MEDICAL CENTER   (United States)

^d BETH ISRAEL DEACONESS MEDICAL CENTER   (United States)

Author keywords

Leptin; Neuroendocrine axes; Neuropsychiatric aspects

Indexed keywords

CORTICOTROPIN; HYDROCORTISONE; LEPTIN; LEPTIN RECEPTOR; THYROTROPIN;

BRAIN DEVELOPMENT; CENTRAL NERVOUS SYSTEM; COGNITION; DEMENTIA; DEPRESSION; DISEASE ASSOCIATION; HUMAN; HYDROCORTISONE RELEASE; HYPERCORTISOLISM; HYPOPHYSIS ADRENAL SYSTEM; HYPOTHALAMUS HYPOPHYSIS ADRENAL SYSTEM; MENTAL DISEASE; NERVE CELL PLASTICITY; NEUROENDOCRINE SYSTEM; NEUROPATHOLOGY; PROGNOSIS; PROTEIN INTERACTION; PSYCHOLOGICAL ASPECT; REVIEW; TREATMENT RESPONSE; HYPOTHALAMUS HYPOPHYSIS SYSTEM; MENTAL STRESS; METABOLISM; PHYSIOLOGY;

COGNITION; HUMANS; HYDROCORTISONE; HYPOTHALAMO-HYPOPHYSEAL SYSTEM; LEPTIN; PITUITARY-ADRENAL SYSTEM; STRESS, PSYCHOLOGICAL;

EID: 84916210495     PISSN: 03064530     EISSN: 18733360     Source Type: Journal    
DOI: 10.1016/j.psyneuen.2014.09.004     Document Type: Review

References (122)

1. Ahima R.S., Prabakaran D., Mantzoros C., Qu D., Lowell B., Maratos-Flier E., Flier J.S. Role of leptin in the neuroendocrine response to fasting. Nature 1996, 382:250-252.
2. Andreasson A., Arborelius L., Erlanson-Albertsson C., Lekander M. A putative role for cytokines in the impaired appetite in depression. Brain Behav. Immun. 2007, 21:147-152.
3. Banks W.A. The many lives of leptin. Peptides 2004, 25:331-338.
4. Besedovsky H.O., del Rey A. Immune-neuro-endocrine interactions: facts and hypotheses. Endocr. Rev. 1996, 17:64-102.
5. Beydoun M.A., Beydoun H.A., Shroff M.R., Kitner-Triolo M.H., Zonderman A.B. Serum leptin, thyroxine and thyroid-stimulating hormone levels interact to affect cognitive function among US adults: evidence from a large representative survey. Neurobiol. Aging 2011, 33:1730-1743.
6. Bhasin S., Cunningham G.R., Hayes F.J., Matsumoto A.M., Snyder P.J., Swerdloff R.S., Montori V.M. Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J. Clin. Endocrinol. Metab. 2010, 95:2536-2559.
7. Bjorntorp P. Do stress reactions cause abdominal obesity and comorbidities?. Obes. Rev. 2001, 2:73-86.
8. Bluher S., Mantzoros C.S. Leptin in humans: lessons from translational research. Am. J. Clin. Nutr. 2009, 89:991S-997S.
9. Bluher S., Shah S., Mantzoros C.S. Leptin deficiency: clinical implications and opportunities for therapeutic interventions. J. Investig. Med. 2009, 57:784-788.
10. Boden G., Chen X., Mozzoli M., Ryan I. Effect of fasting on serum leptin in normal human subjects. J. Clin. Endocrinol. Metab. 1996, 81:3419-3423.
11. Bomba M., Gambera A., Bonini L., Peroni M., Neri F., Scagliola P., Nacinovich R. Endocrine profiles and neuropsychologic correlates of functional hypothalamic amenorrhea in adolescents. Fertil. Steril. 2007, 87:876-885.
12. Bouret S.G., Draper S.J., Simerly R.B. Formation of projection pathways from the arcuate nucleus of the hypothalamus to hypothalamic regions implicated in the neural control of feeding behavior in mice. J. Neurosci. 2004, 24:2797-2805.
13. Bouret S.G., Draper S.J., Simerly R.B. Trophic action of leptin on hypothalamic neurons that regulate feeding. Science 2004, 304:108-110.
14. Bouret S.G., Gorski J.N., Patterson C.M., Chen S., Levin B.E., Simerly R.B. Hypothalamic neural projections are permanently disrupted in diet-induced obese rats. Cell Metab. 2008, 7:179-185.
15. Bouret S.G., Simerly R.B. Minireview: leptin and development of hypothalamic feeding circuits. Endocrinology 2004, 145:2621-2626.
16. Bray G.A., York D.A. Hypothalamic and genetic obesity in experimental animals: an autonomic and endocrine hypothesis. Physiol. Rev. 1979, 59:719-809.
17. Brennan A.M., Lee J.H., Tsiodras S., Chan J.L., Doweiko J., Chimienti S.N., Wadhwa S.G., Karchmer A.W., Mantzoros C.S. r-metHuLeptin improves highly active antiretroviral therapy-induced lipoatrophy and the metabolic syndrome, but not through altering circulating IGF and IGF-binding protein levels: observational and interventional studies in humans. Eur. J. Endocrinol. 2009, 160:173-176.
18. Calderoni S., Muratori F., Leggero C., Narzisi A., Apicella F., Balottin U., Carigi T., Maestro S., Fabbro F., Urgesi C. Neuropsychological functioning in children and adolescents with restrictive-type anorexia nervosa: an in-depth investigation with NEPSY-II. J. Clin. Exp. Neuropsychol. 2013, 35:167-179.
19. Carro E., Senaris R., Considine R.V., Casanueva F.F., Dieguez C. Regulation of in vivo growth hormone secretion by leptin. Endocrinology 1997, 138:2203-2206.
20. Castellano J.M., Tena-Sempere M. Metabolic regulation of kisspeptin. Adv. Exp. Med. Biol. 2013, 784:363-383.
21. Chan J.L., Heist K., DePaoli A.M., Veldhuis J.D., Mantzoros C.S. The role of falling leptin levels in the neuroendocrine and metabolic adaptation to short-term starvation in healthy men. J. Clin. Invest. 2003, 111:1409-1421.
22. Chan J.L., Matarese G., Shetty G.K., Raciti P., Kelesidis I., Aufiero D., De Rosa V., Perna F., Fontana S., Mantzoros C.S. Differential regulation of metabolic, neuroendocrine, and immune function by leptin in humans. Proc. Natl. Acad. Sci. U. S. A. 2006, 103:8481-8486.
23. Chan J.L., Williams C.J., Raciti P., Blakeman J., Kelesidis T., Kelesidis I., Johnson M.L., Thorner M.O., Mantzoros C.S. Leptin does not mediate short-term fasting-induced changes in growth hormone pulsatility but increases IGF-I in leptin deficiency states. J. Clin. Endocrinol. Metab. 2008, 93:2819-2827.
24. Chehab F.F., Lim M.E., Lu R. Correction of the sterility defect in homozygous obese female mice by treatment with the human recombinant leptin. Nat. Genet. 1996, 12:318-320.
25. Chou S.H., Chamberland J.P., Liu X., Matarese G., Gao C., Stefanakis R., Brinkoetter M.T., Gong H., Arampatzi K., Mantzoros C.S. Leptin is an effective treatment for hypothalamic amenorrhea. Proc. Natl. Acad. Sci. U. S. A. 2011, 108:6585-6590.
26. Clement K., Vaisse C., Lahlou N., Cabrol S., Pelloux V., Cassuto D., Gourmelen M., Dina C., Chambaz J., Lacorte J.M., Basdevant A., Bougneres P., Lebouc Y., Froguel P., Guy-Grand B. A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction. Nature 1998, 392:398-401.
27. Costa A., Poma A., Martignoni E., Nappi G., Ur E., Grossman A. Stimulation of corticotrophin-releasing hormone release by the obese (ob) gene product, leptin, from hypothalamic explants. Neuroreport 1997, 8:1131-1134.
28. Dalamaga M., Chou S.H., Shields K., Papageorgiou P., Polyzos S.A., Mantzoros C.S. Leptin at the intersection of neuroendocrinology and metabolism: current evidence and therapeutic perspectives. Cell Metab. 2013, 18:29-42.
29. Dallman M.F., Pecoraro N., Akana S.F., La Fleur S.E., Gomez F., Houshyar H., Bell M.E., Bhatnagar S., Laugero K.D., Manalo S. Chronic stress and obesity: a new view of comfort food. Proc. Natl. Acad. Sci. U. S. A. 2003, 100:11696-11701.
30. Dallman M.F., Pecoraro N.C., la Fleur S.E. Chronic stress and comfort foods: self-medication and abdominal obesity. Brain Behav. Immun. 2005, 19:275-280.
31. de Kloet E.R., Joels M., Holsboer F. Stress and the brain: from adaptation to disease. Nat. Rev. Neurosci. 2005, 6:463-475.
32. Dodd S., Maes M., Anderson G., Dean O.M., Moylan S., Berk M. Putative neuroprotective agents in neuropsychiatric disorders. Prog. Neuropsychopharmacol. Biol. Psychiatry 2013, 42:135-145.
33. Dugbartey A.T. Neurocognitive aspects of hypothyroidism. Arch. Intern. Med. 1998, 158:1413-1418.
34. Esel E., Ozsoy S., Tutus A., Sofuoglu S., Kartalci S., Bayram F., Kokbudak Z., Kula M. Effects of antidepressant treatment and of gender on serum leptin levels in patients with major depression. Prog. Neuropsychopharmacol. Biol. Psychiatry 2005, 29:565-570.
35. Farooqi I.S., Jebb S.A., Langmack G., Lawrence E., Cheetham C.H., Prentice A.M., Hughes I.A., McCamish M.A., O'Rahilly S. Effects of recombinant leptin therapy in a child with congenital leptin deficiency. N. Engl. J. Med. 1999, 341:879-884.
36. Farooqi I.S., Matarese G., Lord G.M., Keogh J.M., Lawrence E., Agwu C., Sanna V., Jebb S.A., Perna F., Fontana S., Lechler R.I., DePaoli A.M., O'Rahilly S. Beneficial effects of leptin on obesity, T cell hyporesponsiveness, and neuroendocrine/metabolic dysfunction of human congenital leptin deficiency. J. Clin. Invest. 2002, 110:1093-1103.
37. Farooqi I.S., Wangensteen T., Collins S., Kimber W., Matarese G., Keogh J.M., Lank E., Bottomley B., Lopez-Fernandez J., Ferraz-Amaro I., Dattani M.T., Ercan O., Myhre A.G., Retterstol L., Stanhope R., Edge J.A., McKenzie S., Lessan N., Ghodsi M., De Rosa V., Perna F., Fontana S., Barroso I., Undlien D.E., O'Rahilly S. Clinical and molecular genetic spectrum of congenital deficiency of the leptin receptor. N. Engl. J. Med. 2007, 356:237-247.
38. Farr S.A., Banks W.A., Morley J.E. Effects of leptin on memory processing. Peptides 2006, 27:1420-1425.
39. Favaro A., Santonastaso P., Manara R., Bosello R., Bommarito G., Tenconi E., Di Salle F. Disruption of visuospatial and somatosensory functional connectivity in anorexia nervosa. Biol. Psychiatry 2012, 72:864-870.
40. Fei H., Okano H.J., Li C., Lee G.H., Zhao C., Darnell R., Friedman J.M. 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):7001-7005.
41. Fiorenza C.G., Chou S.H., Mantzoros C.S. Lipodystrophy: pathophysiology and advances in treatment. Nat. Rev. Endocrinol. 2011, 7:137-150.
42. Fitzgerald P.B., Scaffidi A., Morris M.J., de Castella A.R., Kulkarni J. The relationship of changes in leptin, neuropeptide Y and reproductive hormones to antipsychotic induced weight gain. Hum. Psychopharmacol. 2003, 18:551-557.
43. Flier J.S. Clinical review 94: what's in a name? In search of leptin's physiologic role. J. Clin. Endocrinol. Metab. 1998, 83:1407-1413.
44. Fu L.Y., van den Pol A.N. Kisspeptin directly excites anorexigenic proopiomelanocortin neurons but inhibits orexigenic neuropeptide Y cells by an indirect synaptic mechanism. J. Neurosci. 2010, 30:10205-10219.
45. Fulton S., Pissios P., Manchon R.P., Stiles L., Frank L., Pothos E.N., Maratos-Flier E., Flier J.S. Leptin regulation of the mesoaccumbens dopamine pathway. Neuron 2006, 51:811-822.
46. Fulton S., Woodside B., Shizgal P. Modulation of brain reward circuitry by leptin. Science 2000, 287:125-128.
47. Garza J.C., Guo M., Zhang W., Lu X.Y. Leptin increases adult hippocampal neurogenesis in vivo and in vitro. J. Biol. Chem. 2008, 283:18238-18247.
48. Garza J.C., Guo M., Zhang W., Lu X.Y. Leptin restores adult hippocampal neurogenesis in a chronic unpredictable stress model of depression and reverses glucocorticoid-induced inhibition of GSK-3beta/beta-catenin signaling. Mol. Psychiatry 2011, 17:790-808.
49. Ge J.F., Qi C.C., Zhou J.N. Imbalance of leptin pathway and hypothalamus synaptic plasticity markers are associated with stress-induced depression in rats. Behav. Brain Res. 2013, 249:38-43.
50. Gecici O., Kuloglu M., Atmaca M., Tezcan A.E., Tunckol H., Emul H.M., Ustundag B. High serum leptin levels in depressive disorders with atypical features. Psychiatry Clin. Neurosci. 2005, 59:736-738.
51. Gray J., Yeo G.S., Cox J.J., Morton J., Adlam A.L., Keogh J.M., Yanovski J.A., El Gharbawy A., Han J.C., Tung Y.C., Hodges J.R., Raymond F.L., O'Rahilly S., Farooqi I.S. Hyperphagia, severe obesity, impaired cognitive function, and hyperactivity associated with functional loss of one copy of the brain-derived neurotrophic factor (BDNF) gene. Diabetes 2006, 55:3366-3371.
52. Greco S.J., Bryan K.J., Sarkar S., Zhu X., Smith M.A., Ashford J.W., Johnston J.M., Tezapsidis N., Casadesus G. Leptin reduces pathology and improves memory in a transgenic mouse model of Alzheimer's disease. J. Alzheimers Dis. 2010, 19:1155-1167.
53. Guillemot J., Lukaszewski M.A., Montel V., Delahaye F., Mayeur S., Laborie C., Dickes-Coopman A., Dutriez-Casteloot I., Lesage J., Breton C., Vieau D. Influence of prenatal undernutrition on the effects of clozapine and aripiprazole in the adult male rats: relevance to a neurodevelopmental origin of schizophrenia?. Eur. J. Pharmacol. 2011, 667:402-409.
54. Guo M., Huang T.Y., Garza J.C., Chua S.C., Lu X.Y. Selective deletion of leptin receptors in adult hippocampus induces depression-related behaviours. Int. J. Neuropsychopharmacol. 2012, 16:857-867.
55. Heiman M.L., Ahima R.S., Craft L.S., Schoner B., Stephens T.W., Flier J.S. Leptin inhibition of the hypothalamic-pituitary-adrenal axis in response to stress. Endocrinology 1997, 138:3859-3863.
56. Holsboer F., Ising M. Stress hormone regulation: biological role and translation into therapy. Annu. Rev. Psychol. 2010, 61:81-109.
57. Hryhorczuk C., Sharma S., Fulton S.E. Metabolic disturbances connecting obesity and depression. Front. Neurosci. 2013, 7:177.
58. Intebi A.D., Garau L., Brusco I., Pagano M., Gaillard R.C., Spinedi E. Alzheimer's disease patients display gender dimorphism in circulating anorectic adipokines. Neuroimmunomodulation 2002, 10:351-358.
59. Ishii M., Iadecola C. Abnormal hypothalamic leptin signaling leads to early metabolic dysfunction in mice overexpressing the amyloid precursor protein (P1. 238). Neurology 2014, 82.10(Supplement). P1-238.
60. Johnston J.M., Greco S.J., Hamzelou A., Ashford J.W., Tezapsidis N. Repositioning leptin as a therapy for Alzheimer's disease. Therapy 2011, 8:481-490.
61. Khan S.M., Hamnvik O.P., Brinkoetter M., Mantzoros C.S. Leptin as a modulator of neuroendocrine function in humans. Yonsei Med. J. 2012, 53:671-679.
62. Kloiber S., Ripke S., Kohli M.A., Reppermund S., Salyakina D., Uher R., McGuffin P., Perlis R.H., Hamilton S.P., Putz B., Hennings J., Bruckl T., Klengel T., Bettecken T., Ising M., Uhr M., Dose T., Unschuld P.G., Zihl J., Binder E., Muller-Myhsok B., Holsboer F., Lucae S. Resistance to antidepressant treatment is associated with polymorphisms in the leptin gene, decreased leptin mRNA expression, and decreased leptin serum levels. Eur. Neuropsychopharmacol. 2012, 23:653-662.
63. Koyama K.I., Asakawa A., Nakahara T., Amitani H., Amitani M., Saito M., Taruno Y., Zoshiki T., Cheng K.C., Yasuhara D., Inui A. Intelligence quotient and cognitive functions in severe restricting-type anorexia nervosa before and after weight gain. Nutrition 2012, 28:1132-1136.
64. Lawson E.A., Miller K.K., Blum J.I., Meenaghan E., Misra M., Eddy K.T., Herzog D.B., Klibanski A. Leptin levels are associated with decreased depressive symptoms in women across the weight spectrum, independent of body fat. Clin. Endocrinol. (Oxf.) 2011, 76:520-525.
65. Lee J.H., Chan J.L., Sourlas E., Raptopoulos V., Mantzoros C.S. Recombinant methionyl human leptin therapy in replacement doses improves insulin resistance and metabolic profile in patients with lipoatrophy and metabolic syndrome induced by the highly active antiretroviral therapy. J. Clin. Endocrinol. Metab. 2006, 91:2605-2611.
66. Licinio J., Caglayan S., Ozata M., Yildiz B.O., de Miranda P.B., O'Kirwan F., Whitby R., Liang L., Cohen P., Bhasin S., Krauss R.M., Veldhuis J.D., Wagner A.J., DePaoli A.M., McCann S.M., Wong M.L. 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, 101:4531-4536.
67. Licinio J., Mantzoros C., Negrao A.B., Cizza G., Wong M.L., Bongiorno P.B., Chrousos G.P., Karp B., Allen C., Flier J.S., Gold P.W. Human leptin levels are pulsatile and inversely related to pituitary-adrenal function. Nat. Med. 1997, 3:575-579.
68. Lieb W., Beiser A.S., Vasan R.S., Tan Z.S., Au R., Harris T.B., Roubenoff R., Auerbach S., DeCarli C., Wolf P.A., Seshadri S. Association of plasma leptin levels with incident Alzheimer disease and MRI measures of brain aging. Jr. Am. Med. Assoc. 2009, 302:2565-2572.
69. Liu J., Garza J.C., Bronner J., Kim C.S., Zhang W., Lu X.Y. Acute administration of leptin produces anxiolytic-like effects: a comparison with fluoxetine. Psychopharmacology (Berl.) 2009, 207:535-545.
70. Liu J., Perez S.M., Zhang W., Lodge D.J., Lu X.Y. Selective deletion of the leptin receptor in dopamine neurons produces anxiogenic-like behavior and increases dopaminergic activity in amygdala. Mol. Psychiatry 2011, 16:1024-1038.
71. London E.D., Berman S.M., Chakrapani S., Delibasi T., Monterosso J., Erol H.K., Paz-Filho G., Wong M.L., Licinio J. Short-term plasticity of gray matter associated with leptin deficiency and replacement. J. Clin. Endocrinol. Metab. 2011, 96:E1212-E1220.
72. Lord G.M., Matarese G., Howard J.K., Baker R.J., Bloom S.R., Lechler R.I. Leptin modulates the T-cell immune response and reverses starvation-induced immunosuppression. Nature 1998, 394:897-901.
73. Lu X.Y. The leptin hypothesis of depression: a potential link between mood disorders and obesity?. Curr. Opin. Pharmacol. 2007, 7:648-652.
74. Lu X.Y., Kim C.S., Frazer A., Zhang W. Leptin: a potential novel antidepressant. Proc. Natl. Acad. Sci. U. S. A. 2006, 103:1593-1598.
75. Luque R.M., Huang Z.H., Shah B., Mazzone T., Kineman R.D. Effects of leptin replacement on hypothalamic-pituitary growth hormone axis function and circulating ghrelin levels in ob/ob mice. Am. J. Physiol. Endocrinol. Metab. 2007, 292:E891-E899.
76. Mainardi M., Scabia G., Vottari T., Santini F., Pinchera A., Maffei L., Pizzorusso T., Maffei M. A sensitive period for environmental regulation of eating behavior and leptin sensitivity. Proc. Natl. Acad. Sci. U. S. A. 2010, 107(38):16673-16678.
77. Mainardi M., Pizzorusso T., Maffei M. Environment, leptin sensitivity, and hypothalamic plasticity. Neural Plast. 2013, 2013:438072.
78. Mantzoros C., Flier J.S., Lesem M.D., Brewerton T.D., Jimerson D.C. Cerebrospinal fluid leptin in anorexia nervosa: correlation with nutritional status and potential role in resistance to weight gain. J. Clin. Endocrinol. Metab. 1997, 82:1845-1851.
79. Marazziti D., Rutigliano G., Baroni S., Landi P., Dell'osso L. Metabolic syndrome and major depression. CNS Spectr. 2013, 1-12.
80. Masuzaki H., Ogawa Y., Hosoda K., Miyawaki T., Hanaoka I., Hiraoka J., Yasuno A., Nishimura H., Yoshimasa Y., Nishi S., Nakao K. Glucocorticoid regulation of leptin synthesis and secretion in humans: elevated plasma leptin levels in Cushing's syndrome. J. Clin. Endocrinol. Metab. 1997, 82:2542-2547.
81. McIntyre R.S., Mancini D.A., Basile V.S. Mechanisms of antipsychotic-induced weight gain. J. Clin. Psychiatry 2001, 62(Suppl. 23):23-29.
82. Miell J.P., Englaro P., Blum W.F. Dexamethasone induces an acute and sustained rise in circulating leptin levels in normal human subjects. Horm. Metab. Res. 1996, 28:704-707.
83. Miller G.E., Freedland K.E., Carney R.M., Stetler C.A., Banks W.A. Pathways linking depression, adiposity, and inflammatory markers in healthy young adults. Brain Behav. Immun. 2003, 17:276-285.
84. Miller K.J. The other side of estrogen replacement therapy: outcome study results of mood improvement in estrogen users and nonusers. Curr. Psychiatry Rep. 2003, 5:439-444.
85. Montague C.T., Farooqi I.S., Whitehead J.P., Soos M.A., Rau H., Wareham N.J., Sewter C.P., Digby J.E., Mohammed S.N., Hurst J.A., Cheetham C.H., Earley A.R., Barnett A.H., Prins J.B., O'Rahilly S. Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature 1997, 387:903-908.
86. Moon H.S., Dincer F., Mantzoros C.S. Amylin-induced downregulation of hippocampal neurogenesis is attenuated by leptin in a STAT3/AMPK/ERK-dependent manner in mice. Diabetologia 2013, 56:627-634.
87. Moschos S., Chan J.L., Mantzoros C.S. Leptin and reproduction: a review. Fertil. Steril. 2002, 77:433-444.
88. Musso C., Cochran E., Javor E., Young J., Depaoli A.M., 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, 54:255-263.
89. Myers M.G., Munzberg H., Leinninger G.M., Leshan R.L. The geometry of leptin action in the brain: more complicated than a simple ARC. Cell Metab. 2009, 9:117-123.
90. Nagy G.S., Tsiodras S., Martin L.D., Avihingsanon A., Gavrila A., Hsu W.C., Karchmer A.W., Mantzoros C.S. Human immunodeficiency virus type 1-related lipoatrophy and lipohypertrophy are associated with serum concentrations of leptin. Clin. Infect. Dis. 2003, 36:795-802.
91. Navarro V.M., Kaiser U.B. Metabolic influences on neuroendocrine regulation of reproduction. Curr. Opin. Endocrinol. Diab. Obes. 2013, 20:335-341.
92. Nye E.J., Bornstein S.R., Grice J.E., Tauchnitz R., Hockings G.I., Strakosch C.R., Jackson R.V., Torpy D.J. Interactions between the stimulated hypothalamic-pituitary-adrenal axis and leptin in humans. J. Neuroendocrinol. 2000, 12:141-145.
93. Papaspyrou-Rao S., Schneider S.H., Petersen R.N., Fried S.K. Dexamethasone increases leptin expression in humans in vivo. J. Clin. Endocrinol. Metab. 1997, 82:1635-1637.
94. Pardini V.C., Victoria I.M., Rocha S.M., Andrade D.G., Rocha A.M., Pieroni F.B., Milagres G., Purisch S., Velho G. Leptin levels, beta-cell function, and insulin sensitivity in families with congenital and acquired generalized lipoatropic diabetes. J. Clin. Endocrinol. Metab. 1998, 83:503-508.
95. Paz-Filho G., Wong M.L., Licinio J. The procognitive effects of leptin in the brain and their clinical implications. Int. J. Clin. Pract. 2010, 64:1808-1812.
96. Paz-Filho G.J., Babikian T., Asarnow R., Delibasi T., Esposito K., Erol H.K., Wong M.L., Licinio J. Leptin replacement improves cognitive development. PLoS ONE 2008, 3:e3098.
97. Pinto S., Roseberry A.G., Liu H., Diano S., Shanabrough M., Cai X., Friedman J.M., Horvath T.L. Rapid rewiring of arcuate nucleus feeding circuits by leptin. Science 2004, 304:110-115.
98. Popovic V., Doknic M., Maric N., Pekic S., Damjanovic A., Miljic D., Popovic S., Miljic N., Djurovic M., Jasovic-Gasic M., Dieguez C., Casanueva F.F. Changes in neuroendocrine and metabolic hormones induced by atypical antipsychotics in normal-weight patients with schizophrenia. Neuroendocrinology 2007, 85:249-256.
99. Pralong F.P., Roduit R., Waeber G., Castillo E., Mosimann F., Thorens B., Gaillard R.C. Leptin inhibits directly glucocorticoid secretion by normal human and rat adrenal gland. Endocrinology 1998, 139:4264-4268.
100. Quennell J.H., Mulligan A.C., Tups A., Liu X., Phipps S.J., Kemp C.J., Herbison A.E., Grattan D.R., Anderson G.M. Leptin indirectly regulates gonadotropin-releasing hormone neuronal function. Endocrinology 2009, 150:2805-2812.
101. Reynolds G.P., Kirk S.L. Metabolic side effects of antipsychotic drug treatment - pharmacological mechanisms. Pharmacol. Ther. 2010, 125:169-179.
102. Roubos E.W., Dahmen M., Kozicz T., Xu L. Leptin and the hypothalamo-pituitary-adrenal stress axis. Gen. Comp. Endocrinol. 2012, 177:28-36.
103. Rubin R.T., Rhodes M.E., Czambel R.K. Sexual diergism of baseline plasma leptin and leptin suppression by arginine vasopressin in major depressives and matched controls. Psychiatry Res. 2002, 113:255-268.
104. Sanchez-Margalet V., Martin-Romero C., Santos-Alvarez J., Goberna R., Najib S., Gonzalez-Yanes C. Role of leptin as an immunomodulator of blood mononuclear cells: mechanisms of action. Clin. Exp. Immunol. 2003, 133:11-19.
105. Sanchez V.C., Goldstein J., Stuart R.C., Hovanesian V., Huo L., Munzberg H., Friedman T.C., Bjorbaek C., Nillni E.A. Regulation of hypothalamic prohormone convertases 1 and 2 and effects on processing of prothyrotropin-releasing hormone. J. Clin. Invest. 2004, 114:357-369.
106. Schmidt H.D., Shelton R.C., Duman R.S. Functional biomarkers of depression: diagnosis, treatment, and pathophysiology. Neuropsychopharmacology 2011, 36:2375-2394.
107. Scott M.M., Lachey J.L., Sternson S.M., Lee C.E., Elias C.F., Friedman J.M., Elmquist J.K. Leptin targets in the mouse brain. J. Comp. Neurol. 2009, 514(5):518-532.
108. Schwartz M.W., Woods S.C., Porte D., Seeley R.J., Baskin D.G. Central nervous system control of food intake. Nature 2000, 404:661-671.
109. Shanley L.J., Irving A.J., Harvey J. Leptin enhances NMDA receptor function and modulates hippocampal synaptic plasticity. J. Neurosci. 2001, 21(24):RC186.
110. Sienkiewicz E., Magkos F., Aronis K.N., Brinkoetter M., Chamberland J.P., Chou S., Arampatzi K.M., Gao C., Koniaris A., Mantzoros C.S. Long-term metreleptin treatment increases bone mineral density and content at the lumbar spine of lean hypoleptinemic women. Metabolism 2011, 60:1211-1221.
111. Stanley S., Pinto S., Segal J., Perez C.A., Viale A., DeFalco J., Cai X., Heisler L.K., Friedman J.M. Identification of neuronal subpopulations that project from hypothalamus to both liver and adipose tissue polysynaptically. Proc. Natl. Acad. Sci. U. S. A. 2010, 107:7024-7029.
112. Steppan C.M., Swick A.G. A role for leptin in brain development. Biochem. Biophys. Res. Commun. 1999, 256:600-602.
113. Sternheim L., Startup H., Pretorius N., Johnson-Sabine E., Schmidt U., Channon S. An experimental exploration of social problem solving and its associated processes in anorexia nervosa. Psychiatry Res. 2012, 200:524-529.
114. Strobel A., Issad T., Camoin L., Ozata M., Strosberg A.D. A leptin missense mutation associated with hypogonadism and morbid obesity. Nat. Genet. 1998, 18:213-215.
115. Tsoukas M.A., Farr O.M., Mantzoros C.S. Advances in metabolism. Metabolism 2013, 62:1700-1713.
116. van der Kroon P.H., Boldewijn H., Langeveld-Soeter N. Congenital hypothyroidism in latent obese (ob/ob) mice. Int. J. Obes. 1982, 6:83-90.
117. Vatier C., Gautier J.F., Vigouroux C. Therapeutic use of recombinant methionyl human leptin. Biochimie 2012, 94:2116-2125.
118. Welt C.K., Chan J.L., Bullen J., Murphy R., Smith P., DePaoli A.M., Karalis A., Mantzoros C.S. Recombinant human leptin in women with hypothalamic amenorrhea. N. Engl. J. Med. 2004, 351:987-997.
119. Wierman M.E., Basson R., Davis S.R., Khosla S., Miller K.K., Rosner W., Santoro N. Androgen therapy in women: an Endocrine Society Clinical Practice guideline. J. Clin. Endocrinol. Metab. 2006, 91:3697-3710.
120. Wu M.K., Huang C.Y., Liou Y.J., Wang C.K., Lee S.D. Glucose-insulin homeostasis, lipid profiles and GH-IGF-IGFBP axis in clozapine-treated schizophrenic obesity versus non-psychiatric obesity. Int. J. Obes. (Lond.) 2008, 32:436-442.
121. Yu W.H., Kimura M., Walczewska A., Karanth S., McCann S.M. Role of leptin in hypothalamic-pituitary function. Proc. Natl. Acad. Sci. U. S. A. 1997, 94:1023-1028.
122. Zhang Y., Proenca R., Maffei M., Barone M., Leopold L., Friedman J.M. Positional cloning of the mouse obese gene and its human homologue. Nature 1994, 372:425-432.