Skip to main content
Log in

Leptin

A multifaceted hormone in the central nervous system

  • Published:
Molecular Neurobiology Aims and scope Submit manuscript

Abstract

It is well established that the adipocyte-derived hormone leptin is an important circulating satiety factor that regulates body weight and food intake via its actions on specific hypothalamic nuclei. However, there is growing evidence that leptin and its receptors are widely expressed throughout the brain, in regions not generally associated with energy homeostasis, such as cortex, cerebellum, brainstem, basal ganglia, and hippocampus. In this review the author discusses recent advances made in leptin neurobiology, with particular emphasis on the role of this endocrine peptide in normal and pathophysiological hippocampal function.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Sinha M. K., Opentanova I., Ohannesian J. P., Kolacynski J. W., Hale L., Becker G. W., et al. (1996) Evidence of free and bound leptin in human circulation: studies in lean and obese subjects and during short-term fasting. J. Clin. Invest. 98, 1277–1282.

    PubMed  CAS  Google Scholar 

  2. Maffei M. J., Halaas J., Ravussin E., Pratley R. E., Lee G. M., Zhang Y., et al. (1995) Leptin levels in human and rodent: measurement of plasma leptin and ob mRNA in obese and weight-reduced subjects. Nat. Med. 1, 1155–1161.

    PubMed  CAS  Google Scholar 

  3. Frederich R. C., Hamann A., Anderson S., and Lollman B. (1995) Leptin levels reflect body lipid content in mice: evidence for diet-induced resistance to leptin action. Nat. Med. 1, 1311–1314.

    PubMed  CAS  Google Scholar 

  4. Hamilton B. S., Paglia D., Kwan A. Y. W., and Dietel M. (1995) Increased obese mRNA expression in omental fat cells from massively obese humans. Nat. Med. 1, 953–956.

    PubMed  CAS  Google Scholar 

  5. Elmquist J. K., Elias C. F., and Saper C. B. (1999) From lesions to leptin: hypothalamic control of food intake and body weight. Neuron 22, 221–232.

    PubMed  CAS  Google Scholar 

  6. Schwartz M. W., Peskind E., Raskind M., Boyko E. J., and Porte D. (1996) Cerebrospinal fluid leptin concentrations: relationship to plasma leptin and to adiposity in humans. Nature Med. 2, 589–593.

    PubMed  CAS  Google Scholar 

  7. Banks W. A., Kastin A. J., Huang W., Jaspan J. P., and Maness L. M. (1996) Leptin enters the brain by a saturable transport system independent of insulin. Peptides 17, 305–311.

    PubMed  CAS  Google Scholar 

  8. Banks W. A., Clever C. M., and Farrell C. L. (2000) Partial saturation and regional variation in the blood-to-brain transport of leptin in normal weight mice. Am. J. Physiol. 278, E1158-E1165.

    CAS  Google Scholar 

  9. Morash B., Li A., Murphy P., Wilkinson M., and Ur E. (1999) Leptin gene expression in the brain and pituitary gland. Endocrinol. 140, 5995–5997.

    CAS  Google Scholar 

  10. Ur E., Wilkinson D. A., Morash B. A., and Wilkinson M. (2002) Leptin immunoreactivity is localised to neurons in the rat brain. Neuroendocrinol. 75, 264–272.

    CAS  Google Scholar 

  11. Tartaglia L. A., Dempski M., Weng X., et al. (1995) Identification and expression cloning of a leptin receptor, Ob-R. Cell 83, 1263–1271.

    PubMed  CAS  Google Scholar 

  12. Lee G. H., Proenca R., Montez J. M., Carroll K., and Darvishzadeh J. G. (1996) Abnormal splicing of the leptin receptor in diabetic mice. Nature 379, 632–635.

    PubMed  CAS  Google Scholar 

  13. Wang M.-Y., Zhou Y. T., Newgard C. B., and Unger R. H. (1998) A novel leptin receptor isoform in rat. FEBS Lett. 392, 87–90.

    Google Scholar 

  14. Chen H., Charlat O., Tartaglia L. A., et al. (1996) Evidence that the diabetes gene encodes the leptin receptor: identification of a mutation in the leptin receptor gene in db/db mice. Cell 84, 491–495.

    PubMed  CAS  Google Scholar 

  15. Zhang Y., Proenca R., Maffei M., Barone M., Leopold L., and Friedman J. M. (1994) Positional cloning of the mouse obese gene and its human homologue. Nature 372, 425–432.

    PubMed  CAS  Google Scholar 

  16. Pellymounter M. A., Culen M. J., Baker M. B., Hecht R., Winters D., Boone T., and Colins F. (1995) Effects of the obese gene product on body weight regulation in ob/ob mice. Science 269, 540–543.

    Google Scholar 

  17. Halaas J. L., Gajiwala K. S., Maffei M., et al. (1995) Weight reducing effects of the plasma protein encoded by the obese gene. Science 269, 543–546.

    PubMed  CAS  Google Scholar 

  18. Campfield L. A., Smith F. J., Guisez Y., Devos R., and Burn P. (1995) Recombinant mouse OB protein: evidence for a peripheral signal linking adiposity and central neural networks. Science 269, 546–549.

    PubMed  CAS  Google Scholar 

  19. Da Silva B. A., Bjorbaek C., Uotani S., and Flier J. S. (1998) Functional properties of leptin receptor isoforms containing the gln > pro extracellular domain mutation of the fatty rat. Endocrinol. 139, 3681–3690.

    Google Scholar 

  20. Clement K., Vaisse C., Lahlous N., Cabroll S., and Pelloux V. (1998) A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction. Nature 392, 398–401.

    PubMed  CAS  Google Scholar 

  21. Tartaglia L. A. (1997) The leptin receptor. J. Biol. Chem. 272, 6093–6096.

    PubMed  CAS  Google Scholar 

  22. Kile B. T. and Alexander W. S. (2001) The suppressors of cytokine signaling (SOCS). Cell. Mol. Life Sci. 58, 1627–1635.

    PubMed  CAS  Google Scholar 

  23. Ihle J. N. (1995) Cytokine receptor signaling. Nature 377, 591–594.

    PubMed  CAS  Google Scholar 

  24. Myers M. G. and White M. F. (1996) Insulin signal transduction and the IRS proteins. Ann. Rev. Pharmacol. Toxicol. 36, 615–658.

    CAS  Google Scholar 

  25. Baumann H., Morella K. K., White D. W., et al. (1996) The full length leptin receptor has signaling capabilities of interleukin 6-type cytokine receptors. Proc. Natl. Acad. Sci. 93, 8374–8378.

    PubMed  CAS  Google Scholar 

  26. Bjorbaek C., Uotani S., da Silva B., and Flier J. S. (1997) Divergent signaling capacities of the long and short isoforms of the leptin receptor. J. Biol. Chem. 272, 32,686–32,695.

    CAS  Google Scholar 

  27. Ghilardi N. and Skoda R. C. (1997) The leptin receptor activates janus tyrosine kinase 2 and signals for proliferation in a factor-dependent cell line. Mol. Endocrinol. 11, 393–399.

    PubMed  CAS  Google Scholar 

  28. Kloek C., Haq A. K., Dunn S. L., Lavery H. J., Banks A. S., and Myers M. G. (2002) Regulation of JAK kinases by intracellular leptin receptor sequences. J. Biol. Chem. 277, 41,547–41,555.

    CAS  Google Scholar 

  29. Carpenter L. R., Farruggella T. J., Symes A., Karow M. L., Yancopoulos G. D., and Stahl N. (1998) Enhancing leptin response by preventing SH2-containing phosphatase 2 interaction with Ob receptor. Proc. Natl. Acad. Sci. 95, 6061–6066.

    PubMed  CAS  Google Scholar 

  30. Li C. and Friedman J. M. (1999) Leptin receptor activation of SH2 domain-containing protein tyrosine phosphatase 2 modulates Ob receptor signal transduction. Proc. Natl. Acad. Sci. 96, 9677–9682.

    PubMed  CAS  Google Scholar 

  31. Morton N. M., Emilsson V., Liu Y. L., and Cawthorne M. A. (1999) Leptin action in intestinal cells. J. Biol. Chem. 273, 26,194–26,201.

    Google Scholar 

  32. Vaisse C., Halaas J. L., Horvath C. M., Darnell J. E., Stoffel M., and Friedman J. M. (1996) Leptin activation of STAT3 in the hypothalamus of wild type and ob/ob mice but not db/db mice. Nature Gen. 14, 95–97.

    CAS  Google Scholar 

  33. Hubschle T., Thom E., Watson A., Roth J., Klaus S., and Meyerhof W. (2001) Leptin-induced translocation of STAT3 immunoreactivity in hypothalamic nuclei involved in body weight regulation. J. Neurosci. 21, 2413–2424.

    PubMed  CAS  Google Scholar 

  34. Bjorbaek C., Elmquist J. K., Frantz J. D., Shoelson S. E., and Flier J. S. (1998) Identification of SOCS-3 as a potential mediator of leptin resisitance. Mol. Cell. 1, 619–625.

    PubMed  CAS  Google Scholar 

  35. Bates S. H., Stearns W. H., Dundon T. A., et al. (2003) STAT3 signalling is required for leptin regulation of energy balance but not reproduction. Nature 421, 856–859.

    PubMed  CAS  Google Scholar 

  36. Bjorbaek C., El-Haschimi K., Frantz J. D., and Flier J. S. (1999) The role of SOCS3 in leptin signaling and resistance. J. Biol. Chem. 274, 30,059–30,065.

    CAS  Google Scholar 

  37. Bjorbaek C., Lavery H. J., Bates S. H., et al. (2000) SOCS3 mediates feedback inhibition of the leptin receptor via Tyr985. J. Biol. Chem. 275, 40,649–40,657.

    CAS  Google Scholar 

  38. Spanwick D., Smith M. A., Groppi V., Logan S. D., and Ashford M. L. J. (1997) Leptin inhibits hypothalamic neurons by activation of ATP-sensitive potassium channels. Nature 390, 521–525.

    Google Scholar 

  39. Keiffer T. J., Heller R. S., Leech C. A., Holz G. G., and Habener J. (1997) Leptin suppression of insulin secretion by activation of ATP-sensitive K+ channels in pancreatic beta cells. Diabetes 46, 1087–1093.

    Google Scholar 

  40. Harvey J., McKenna F., Herson P. S., Spanswick D., and Ashford M. L. J. (1997) Leptin activates ATP-sensitive potassium channels in the rat insulin-secreting cell line, CRI-GI. J. Physiol. 504, 527–535.

    PubMed  CAS  Google Scholar 

  41. Janmey P. (1998) The cytoskeleton and cell signalling: component localisation and mechanical coupling. Physiol. Rev. 78, 763–781.

    PubMed  CAS  Google Scholar 

  42. Harvey J., Hardy S. C., and Ashford M. L. J. (2000) Leptin activation of KATP channels in rat CRI-GI insulinoma cells involves disruption of the cytoskeleton. J. Physiol. 527, 95–107.

    PubMed  CAS  Google Scholar 

  43. Zhao A. Z., Bornfeldt K. E., and Beavo J. A. (1998) Leptin inhibits insulin secretion by activation of phosphodiesterase 3B. J. Clin. Invest. 102, 869–873.

    PubMed  CAS  Google Scholar 

  44. Zhao A. Z., Huan J. N., Gupta S., Pal R., and Sahu A. (2002) A phosphatidylinositol 3-kinase phosphodiesterase 3B-cyclic AMP pathway in hypothalamic action of leptin on feeding. Nat. Neurosci. 5, 727–728.

    PubMed  CAS  Google Scholar 

  45. Tanabe K., Okuya S., Tanizawa Y., Matsutani A., and Oka Y. (1997) Leptin induces proliferation of pancreatic beta cell line, MIN6 through activation of mitogen-activated protein kinase. Biochem. Biophys. Res. Comm. 241, 765–768.

    PubMed  CAS  Google Scholar 

  46. Takahashi Y., Okimura Y., Mizuno I., et al. (1997) Leptin induces mitogen-activated protein kinase-dependent proliferation of C1H10T1/2 cells. J. Biol. Chem. 272, 12,897–12,900.

    CAS  Google Scholar 

  47. Banks A. S., Davies S. M., Bates S. H., and Myers M. G. (2000) Activation of downstream signals by the long form of the leptin receptor. J. Biol. Chem. 275, 14,653–14,672.

    Google Scholar 

  48. Machinal-Quelin F., Dieudonne M. N., Leneveu M. C., Pecquery R., and Giudicelli Y. (2002) Proadipogenic effect of leptin on rat preadipocytes in vitro: activation of MAPK and STAT3 signalling pathways. Am. J. Physiol. 282, C853–863.

    CAS  Google Scholar 

  49. Takekoshi K., Ishii K., Kawakami Y., Isobe K., Nanmoku T., and Nakai T. (2001) Ca2+ mobilisation, tyrosine hydroxylase activity and signalling mechanisms in cultured porcine adrenal medullary chromaffin cells: effects of leptin. Endocrinol. 142, 290–298.

    CAS  Google Scholar 

  50. Martin-Romero C. and Sanchez-Margalet V. (2001) Human leptin activates PI3K and MAPK pathways in human peripheral blood mononuclear cells: possible role of Sam68. Cell. Immunol. 212, 83–91.

    PubMed  CAS  Google Scholar 

  51. Yamashita T., Murakami T., Otani S., Kuwajima M., and Shima K. (1998) Leptin receptor signal transduction: ObRa and ObRb of a fa type. Biochem. Biophys. Res. Comm. 246, 752–759.

    PubMed  CAS  Google Scholar 

  52. Hileman S. M., Pieroz D. D., Masuzaki H., et al. (2002) Characterisation of short isoforms of the leptin receptor in rat cerebral microvessels and of brain uptake of leptin in mouse models of obesity. Endocrinol. 143, 775–783.

    CAS  Google Scholar 

  53. Cohen B., Novick D., and Rubinstein M. (1996) Modulation of insulin activities by leptin. Science 274, 1185–1188.

    PubMed  CAS  Google Scholar 

  54. Szanto I. and Khan C. R. (2000) Selective interaction between leptin and insulin signaling pathways in a hepatic cell line. Proc. Natl. Acad. Sci. 97, 2355–2360.

    PubMed  CAS  Google Scholar 

  55. Harvey J. and Ashford M. L. J. (1998) Insulin occludes leptin activation of ATP-sensitive K+ channels in rat CRI-Gl insulin-secreting cells. J. Physiol. 511, 695–706.

    PubMed  CAS  Google Scholar 

  56. Kellerer M., Lammers R., Fritsche A., et al. (2001) Insulin inhibits leptin receptor signaling in HEK293 cells at the level of JAk2: a potential mechanism for hyperinsulinaemia-associated leptin resistance. Diabetol. 44, 1125–1132.

    CAS  Google Scholar 

  57. Spanswick D., Smith M. A., Mirshamsi S., Routh V. H., and Ashford M. L. J. (2000) Insulin activates ATP-sensitive K+ channels in hypothalamic neurons of lean, but not obese rats. Nat. Neurosci. 3, 757–758.

    PubMed  CAS  Google Scholar 

  58. Niswender K. D. and Schwartz M. W. (2003) Insulin and leptin revisited: adiposity signals with overlapping physiological and intracellular signalling capabilities. Front. Neuroendocrinol. 24, 1–10.

    PubMed  CAS  Google Scholar 

  59. Carvalheira J. B., Siloto R. M., Ignacchitti I., et al. (2001) Insulin modulates leptin-induced STAT3 activation in rat hypothalamus. FEBS Lett. 500, 119–124.

    PubMed  CAS  Google Scholar 

  60. Hakansson M.-L., Hulting A. L., and Meister B. (1996) Expression of leptin receptor mRNA in the hypothalamic arcuate nucleus-relationship with NPY neurons. Neuroreport 7, 3087–3092.

    PubMed  CAS  Google Scholar 

  61. Hakansson M.-L., Brown H., Ghilardi N., Skoda R. C., and Meister B. J. (1998) Leptin receptor immunoreactivity in chemically-defined target neurons of the hypothalamus. J. Neurosci. 18, 559–572.

    PubMed  CAS  Google Scholar 

  62. Elmquist J. K., Bjorbaek C., Ahima R. S., Flier J. S., and Saper C. B. (1998) Distributions of leptin receptor mRNA isoforms in the rat brain. J. Comp. Neurol. 395, 535–547.

    PubMed  CAS  Google Scholar 

  63. Savioz A., Charnay Y., Huguenin C., Graviou C., Greggio B., and Bouras C. (1997) Expression of leptin receptor mRNA (long form slice variant) in the human cerebellum. Neuroreport 8, 3123–3126.

    PubMed  CAS  Google Scholar 

  64. Burguera B., Counc M. E., Long J., et al. (2000) The long form of the leptin receptor (Ob-Rb) is widely expressed in the human brain. Neuroendocrinol. 71, 187–195.

    CAS  Google Scholar 

  65. Dawson R., Pellymounter M., Millard W., Liu S., and Eppler B. (1996) Attenuation of leptin-mediated effects by monosodium glutamate-induced arcuate nucleus damage. Am. J. Physiol. 273, E202-E206.

    Google Scholar 

  66. Baskin D. G., Seeley R. J., Kuijper J. L., et al. (1998) Increased expression of mRNA for the long form of the leptin receptor in the hypothalamus is associated with leptin hypersensitivity and fasting. Diabetes 47, 538–543.

    PubMed  CAS  Google Scholar 

  67. Lin S., Storlien L. H., and Huang X. F. (2000) Leptin receptor, NPY, POMC mRNA expression in the diet-induced obese mouse brain. Brain Res. 875, 89–95.

    PubMed  CAS  Google Scholar 

  68. Mercer J. G., Hoggard N., Williams L. M., Lawrence C. B., Hannah L. T., and Trayhurn P. (1996) Localisation of leptin receptor mRNA and the long form splice variant (Ob-Rb) in mouse hypothalamus and adjacent brain regions by in situ hybridization. FEBS Lett. 387, 113–166.

    PubMed  CAS  Google Scholar 

  69. Baskin D. G., Schwartz M. W., Seeley R. J., et al. (1999) Leptin receptor long-form slice variant protein expression in neuron cell bodies of the brain and colocalisation with neuropeptide Y mRNA in the arcuate nucleus. J. Hist. Cytochem. 47, 353–362.

    CAS  Google Scholar 

  70. Haung X. F., Koutcherov I., Lin S., Wang H. Q., and Storlien L. (1996) Localisation of leptin receptor mRNA expression in mouse brain. Neuroreport 7, 2635–2638.

    Google Scholar 

  71. Lin S. and Huang X. F. (1997) Fasting increases leptin receptor mRNA expression in lean but not obese (ob/ob) mouse brain. Neuroreport 8, 3625–3629.

    PubMed  CAS  Google Scholar 

  72. Bliss T. V. P. and Collingridge G. L. (1993) A synaptic model of memory: long-term potentiation in the hippocampus. Nature 361, 31–39.

    PubMed  CAS  Google Scholar 

  73. Shepherd P. R., Withers D. W., and Siddle K. (1998) Phosphoinositide 3-kinase: the key switch mechanism in insulin signalling. Biochem. J. 333, 417–490.

    Google Scholar 

  74. Liu L., Brown J. C., Webster W. W., Morrisett R. A., and Monoghan D. T. (1995) Insulin potentiates N-methyl-d-aspartate receptor activity in Xenopus oocytes and rat hippocampus. Neurosci. Lett. 192, 5–8.

    PubMed  CAS  Google Scholar 

  75. Chen C. and Leonard J. P. (1996) Protein tyrosine kinase-mediated potentiation of currents cloned from NMDA receptors. J. Neurochem. 67, 194–200.

    PubMed  CAS  Google Scholar 

  76. Liao G. Y. and Leonard J. P. (1999) Insulin modulation of cloned mouse NMDA receptor currents in Xenopus oocytes. J. Neurochem. 73, 1510–1519.

    PubMed  CAS  Google Scholar 

  77. Gispen W. H. and Biessels G. J. (2000) Cognition and synaptic plasticity in diabetes mellitus. TINS 23, 542–549.

    PubMed  CAS  Google Scholar 

  78. Li X. L., Aou S., Oomura Y., Hori N., Fukunaga K., and Hori T. (2002) Impairment of long-term potentiation and spatial memory in leptin-receptor deficient rodents. Neurosci. 113, 607–615.

    CAS  Google Scholar 

  79. Lau L. F. and Huganir R. L. (1995) Differential tyrosine phosphorylation of N-methyl-d-aspartate receptor subunits. J. Biol. Chem. 270, 20,036–20,041.

    CAS  Google Scholar 

  80. Moon I. S., Apperson M. L., and Kennedy M. B. The major tyrosine phosphorylated protein in the postsynaptic density fraction is N-methyl-d-aspartate receptor subunit 2B. Proc. Natl. Acad. Sci. 91, 3954–3958.

  81. Salter M. W. (1998) Src, N-methyl-d-aspartate (NMDA) receptors and synaptic plasticity. Biochem. Pharmacol. 56, 789–798.

    PubMed  CAS  Google Scholar 

  82. Herron C. E., Lester R. A., Coan E. J., and Collingridge G. L. (1986) Frequency-dependent involvement of NMDA receptors in the hippocampus: a novel synaptic mechanism. Nature 322, 265–268.

    PubMed  CAS  Google Scholar 

  83. Spanswick D., Smith M. A., Groppi V., Logan S. D., and Ashford M. L. J. (1997) Leptin inhibits hypothalamic neurons by activation of ATP-sensitive potassium channels. Nature 390, 521–525.

    PubMed  CAS  Google Scholar 

  84. Alger B. E., and Williamson A. A. (1988) A transient calcium-dependent potassium component of the epileptiform burst after-hyperpolarisation in rat hippocampus. J. Physiol. 399, 191–205.

    PubMed  CAS  Google Scholar 

  85. Shao L. R., Halvorsrud R., Borg-Graham L., and Storm J. F. (1999) The role of BK-type Ca2+-dependent K+ channels in spike broadening during repetitive firing in rat hippocampal pyramidal cells. J. Physiol. 521, 135–146.

    PubMed  CAS  Google Scholar 

  86. Kohling R., Vreugdenhil M., Bracci E., and Jefferys J. G. (2000) Ictal epileptiform activity is facilitated by hippocampal GABAA receptor-mediated oscillations. J. Neurosci. 20, 6820–6829.

    PubMed  CAS  Google Scholar 

  87. Abele A. E., Scholz K. P., Scholz W. K., and Miller R. J. (1990) Excitotoxicity induced by enhanced neurotransmission in cultured hippocampal pyramidal neurons. Neuron 4, 413–419.

    PubMed  CAS  Google Scholar 

  88. McLeod J. R., Shen M., Kim D. J., and Thayer S. A. (1998) Neurotoxicity mediated by aberrant patterns of synaptic activity between rat hippocampal neurons in culture. J. Neurophysiol. 80, 2688–2698.

    PubMed  CAS  Google Scholar 

  89. Masuzaki H., Ogawa Y., Sagawa N., et al. (1997) Non-adipose production of leptin: leptin as a novel placenta-derived hormone in humans. Nat. Med. 3, 1029–1033.

    PubMed  CAS  Google Scholar 

  90. Hoggard N., Hunter L., Duncan J. S., Williams L. M., Trayhurn P., and Mercer J. G. (1997) Leptin and leptin receptor mRNA and protein expression in the urine fetus and placenta. Proc. Natl. Acad. Sci. 94, 11,073–11,078.

    CAS  Google Scholar 

  91. Akerman F., Lei Z. M., and Rao C. V. (2002) Human umbilical cord and fetal membranes co-express leptin and its receptor genes. Gynecol. Endocrinol. 16, 299–306.

    PubMed  CAS  Google Scholar 

  92. Camand O., Turban S., Abitbol M., and Guerre-Millo M. (2002) Embryonic expression of the leptin receptor gene in mesoderm-derived tissues. C. R. Biol. 325, 77–87.

    PubMed  CAS  Google Scholar 

  93. Sierra-Honigmann M. R., Nath A. K., Murakami C., et al. (1998) Biological actions of leptin as an angiogenic factor. Science 281, 1683–1686.

    PubMed  CAS  Google Scholar 

  94. Park H. Y., Kwon H. M., Lim H. J., et al. (2001) Potential role of leptin in angiogenesis: leptin induces endothelial cell proliferation and expression of matrix matelloproteinases in vivo and in vitro. Exp. Mol. Med. 33, 95–102.

    PubMed  CAS  Google Scholar 

  95. Goetze S., Bungenstock A., Czupalla C., et al. (2002) Leptin induced endothelial cell migration through Akt, which is inhibited by PPAR gamma ligands. Hypertension 40, 748–754.

    PubMed  CAS  Google Scholar 

  96. Chen S. C., Kochan J. P., Campfield L. A., Burn P., and Smeyne R. J. (1999) Splice variants of the OB receptor gene are differentially expressed in brain and peripheral tissues of mice. J. Recept. Signal Trans. Res. 19, 245–266.

    CAS  Google Scholar 

  97. Chen S. C., Cunningham J. J., and Smeyne R. J. (2000) Expression of OB receptor splice variants during prenatal development of the mouse. J. Recept. Signal Trans. Res. 20, 87.

    CAS  Google Scholar 

  98. Matsuda J., Yokota I., Tsuruo Y., Murakami T., Ishimura K., Shima K., and Kuroda Y. (1999) Development changes in long form leptin receptor expression and localisation in rat brain. Endocrinol. 140, 5233–5238.

    CAS  Google Scholar 

  99. Udagawa J., Hatta T., Naora H., and Otani H. (2000) Expression of the long form of leptin receptor (Ob-Rb) mRNA in the brain of mouse embryos and newborn mice. Brain Res. 868, 251–258.

    PubMed  CAS  Google Scholar 

  100. Ahima R. S., Bjorbaek C., Osei S., and Flier J. S. (1999) Regulation of neuronal and glial proteins by leptin: implications for brain development. Endocrinol. 140, 2755–2762.

    CAS  Google Scholar 

  101. Steppan C. M. and Swick A. G. (1999) A role for leptin in brain development. Biochem. Biophys. Res. Comm. 24, 600–602.

    Google Scholar 

  102. Sena A., Sarlieve L. L., and Rebel G. (1985) Brain myelin of genetically obese mice. J. Neurol. Sci. 68, 233–243.

    PubMed  CAS  Google Scholar 

  103. Bereiter D. A. and Jeanrenaud B. (1980) Altered dendritic orientation of hypothalamic neurons from genetically obese (ob/ob) mice. Brain Res. 202, 201–206.

    PubMed  CAS  Google Scholar 

  104. Bereiter D. A. and Jeanrenaud B. (1979) Altered anatomical organisation in the central nervous system of genetically obese (ob/ob) mouse. Brain Res. 165, 249–260.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jenni Harvey.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Harvey, J. Leptin. Mol Neurobiol 28, 245–258 (2003). https://doi.org/10.1385/MN:28:3:245

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1385/MN:28:3:245

Index Entries

Navigation