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 Article
  • Published:

The weight of leptin in immunity

Nature Reviews Immunology volume 4, pages 371–379 (2004)Cite this article

Key Points

  • Leptin is a hormone that mainly regulates body weight by stimulating energy expenditure through increased thermogenesis and by suppressing intake of food.

  • Leptin is also a pro-inflammatory cytokine that belongs to the family of long-chain helical cytokines and has structural similarity with interleukin-6 (IL-6), IL-12, IL-15, granulocyte colony-stimulating factor (G-CSF), oncostatin M (OSM), prolactin and growth hormone. Because of its dual nature as a hormone and cytokine, leptin links the neuroendocrine system to the immune system.

  • The leptin receptor, OBR, is a member of the class I cytokine receptor family (which includes receptors for IL-6, IL-12, OSM and prolactin) and exists in at least six alternatively spliced forms. The short forms seem to mediate the transport and degradation of leptin. The long form, known as OBRb, is expressed by the hypothalamus in areas that are responsible for the secretion of neuropeptides and neurotransmitters that regulate appetite. OBRb is also expressed by the ovary, pancreatic β-cells, endothelial cells, CD34+ haematopoietic bone-marrow precursors, monocytes/macrophages, and T and B cells.

  • Leptin influences innate immune responses by promoting the activation of monocytes/macrophages, chemotaxis and activation of neutrophils, and the development and activation of natural killer cells.

  • Leptin influences adaptive immunity by increasing the expression of adhesion molecules by CD4+ T cells, promoting proliferation and secretion of IL-2 by naive CD4+ T cells and promoting a bias towards T helper 1-cell responses on memory CD4+ T cells.

  • Leptin-deficient (ob/ob) mice and humans with congenital deficiency of leptin have both metabolic disturbances and immune abnormalities, including abnormal cytokine secretion and thymic hypotrophy. These immune disturbances are corrected by administration of recombinant leptin in both mice and humans.

  • A possible role of leptin in autoimmunity is suggested by the observation that ob/ob mice are protected from several experimental autoimmune diseases and that administration of exogenous leptin to mice that are genetically susceptible to develop autoimmune disease anticipates onset and accelerates the progression of autoimmune responses.

Abstract

Leptin is an adipocyte-derived hormone/cytokine that links nutritional status with neuroendocrine and immune functions. As a hormone, leptin regulates food intake and basal metabolism, and is sexually dimorphic — that is, its serum concentration is higher in females than in males with a similar body fat mass. As a cytokine, leptin can affect thymic homeostasis and the secretion of acute-phase reactants such as interleukin-1 and tumour-necrosis factor. Similar to other pro-inflammatory cytokines, leptin promotes T helper 1 (TH1)-cell differentiation and can modulate the onset and progression of autoimmune responses in several animal models of disease. Here, we review the advances and controversy for a role of leptin in the pathophysiology of immune responses.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

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

Figure 1: Central and peripheral neuroendocrine effects of leptin.
Figure 2: Effects of leptin on innate and adaptive immune responses.
Figure 3: Three-dimensional structure of leptin.
Figure 4: Signalling pathways activated by the leptin receptor.
Figure 5: Schematic model for a role of leptin in autoimmunity.

Similar content being viewed by others

References

  1. Friedman, J. M. & Halaas, J. L. Leptin and the regulation of body weight in mammals. Nature 395, 763–770 (1998).

    Article  CAS  PubMed  Google Scholar 

  2. Matarese, G. et al. Balancing susceptibility to infection and autoimmunity: a role for leptin? Trends Immunol. 23, 182–187 (2002).

    Article  CAS  PubMed  Google Scholar 

  3. Chehab, F., Lim, M. & Lu, R. Correction of the sterility defect in homozygous obese female mice by treatment with the human recombinant leptin. Nature Genet. 12, 318–320 (1996).

    Article  CAS  PubMed  Google Scholar 

  4. Bennett, B. D. et al. A role for leptin and its cognate receptor in hematopoiesis. Curr. Biol. 6, 1170–1180 (1996).

    Article  CAS  PubMed  Google Scholar 

  5. Sierra-Honigmann, M. R. et al. Biological action of leptin as an angiogenic factor. Science 281, 1683–1686 (1998).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  7. Ducy, P. et al. Leptin inhibits bone formation through a hypothalamic relay: a central control of bone mass. Cell 100, 197–207 (2000).

    Article  CAS  PubMed  Google Scholar 

  8. Lord, G. M. et al. Leptin modulates the T-cell immune response and reverses starvation-induced immunosuppression. Nature 394, 897–901 (1998). The first demonstration that leptin modulates CD4+ T-cell responses and is involved in starvation-induced immunosuppression.

    Article  CAS  PubMed  Google Scholar 

  9. Sanchez-Margalet, V. et al. Role of leptin as an immunomodulator of blood mononuclear cells: mechanisms of action. Clin. Exp. Immunol. 133, 11–19 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Turnbull, A. V. & Rivier, C. L. Regulation of the hypothalamic–pituitary–adrenal axis by cytokines: actions and mechanisms of action. Physiol. Rev. 79, 1–71 (1999).

    Article  CAS  PubMed  Google Scholar 

  11. Haddad, J. J. et al. Cytokines and neuro-immune-endocrine interactions: a role for the hypothalamic–pituitary–adrenal revolving axis. J. Neuroimmunol. 133, 1–19 (2002).

    Article  CAS  PubMed  Google Scholar 

  12. Zhang, Y. et al. Positional cloning of the mouse obese gene and its human homologue. Nature 372, 425–432 (1994). This study reports the cloning of the gene encoding leptin in mice and humans.

    Article  CAS  PubMed  Google Scholar 

  13. Landman, R. E. et al. Endotoxin stimulates leptin in the human and nonhuman primate. J. Clin. Endocrinol. Metab. 88 1285–1291 (2003).

    Article  CAS  PubMed  Google Scholar 

  14. Grunfeld, C. et al. Endotoxin and cytokines induce expression of leptin, the ob gene product, in hamsters. A role for leptin in the anorexia of infection. J. Clin. Invest. 97, 2152–2160 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Sarraf, P. et al. Multiple cytokines and acute inflammation raise mouse leptin levels: potential role in inflammatory anorexia. J. Exp. Med. 185, 171–180 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Fantuzzi, G. & Faggioni, R. Leptin in the regulation of immunity, inflammation, and hematopoiesis. J. Leukoc. Biol. 68, 437–446 (2000).

    CAS  PubMed  Google Scholar 

  17. Bullo, M., Garcia-Lorda, P., Megias, I. & Salas-Salvado, J. Systemic inflammation, adipose tissue tumor necrosis factor, and leptin expression. Obes. Res. 11, 525–531 (2003).

    Article  CAS  PubMed  Google Scholar 

  18. Arnalich, F. et al. Relationship of plasma leptin to plasma cytokines and human survivalin sepsis and septic shock. J. Infect. Dis. 180, 908–911 (1999).

    Article  CAS  PubMed  Google Scholar 

  19. Orbak, Z., Ertekin, V., Akay, F., Ozkan, B. & Ors, R. Serum leptin levels in neonatal septicemia. J. Pediatr. Endocrinol. Metab. 16, 727–731 (2003).

    Article  CAS  PubMed  Google Scholar 

  20. Bornstein, S. R., Preas, H. L., Chrousos, G. P. & Suffredini, A. F. Circulating leptin levels during acute experimental endotoxiemia and antiinflammatory therapy in humans. J. Infect. Dis. 178, 887–890 (1998).

    Article  CAS  PubMed  Google Scholar 

  21. Koc, E. et al. Serum leptin levels and their relationship to tumor necrosis factor-α and interleukin-6 in neonatal sepsis. J. Pediatr. Endocrinol. Metab. 16, 1283–1287 (2003).

    Article  CAS  PubMed  Google Scholar 

  22. Yarasheski, K. E. et al. Serum leptin concentrations in human immunodeficiency virus-infected men with low adiposity. Metabolism 46, 303–305 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Bruun, J. M. et al. Effects of pro-inflammatory cytokines and chemokines on leptin production in human adipose tissue in vitro. Mol. Cell. Endocrinol. 190, 91–99 (2002).

    Article  CAS  PubMed  Google Scholar 

  24. Gerhardt, C. C. et al. Chemokines control fat accumulation and leptin secretion by cultured human adipocytes. Mol. Cell. Endocrinol. 175, 81–92 (2001).

    Article  CAS  PubMed  Google Scholar 

  25. Zhang, F. et al. Crystal structure of the obese protein leptin-E100. Nature 387, 206–208 (1997). This paper describes the crystal structure of leptin.

    Article  CAS  PubMed  Google Scholar 

  26. Tartaglia, L. A. et al. Identification and expression cloning of a leptin receptor, Ob-R. Cell 83, 1263–1270 (1995). This study reports the cloning of the gene encoding the leptin receptor.

    Article  CAS  PubMed  Google Scholar 

  27. Tartaglia, L. A. The leptin receptor. J. Biol. Chem. 272, 6093–6100 (1997).

    Article  CAS  PubMed  Google Scholar 

  28. Banks, A. S., Davis, S. M., Bates, S. H. & Myers, M. G. Activation of downstream signals by the long form of the leptin receptor. J. Biol. Chem. 275, 14563–14572 (2000).

    Article  CAS  PubMed  Google Scholar 

  29. Bjorbaek, C. et al. Divergent roles of SHP-2 in ERK activation by leptin receptors. J. Biol. Chem. 276, 4747–4755 (2001).

    Article  CAS  PubMed  Google Scholar 

  30. Sweeney, G. Leptin signalling. Cell Signal. 14, 655–663 (2002).

    Article  CAS  PubMed  Google Scholar 

  31. Mancuso, P. et al. Leptin-deficient mice exhibit impaired host defense in Gram-negative pneumonia. J. Immunol. 168, 4018–4024 (2002).

    Article  CAS  PubMed  Google Scholar 

  32. Zarkesh-Esfahani, H. et al. High-dose leptin activates human leukocytes via receptor expression on monocytes. J. Immunol. 167, 4593–4599 (2001).

    Article  CAS  PubMed  Google Scholar 

  33. Dixit, V. D., Mielenz, M., Taub, D. D. & Parvizi, N. Leptin induces growth hormone secretion from peripheral blood mononuclear cells via a protein kinase C- and nitric oxide-dependent mechanism. Endocrinology 144, 5595–5603 (2003).

    Article  CAS  PubMed  Google Scholar 

  34. Caldefie-Chezet, F., Poulin, A., Tridon, A., Sion, B. & Vasson, M. P. Leptin: a potential regulator of polymorphonuclear neutrophil bactericidal action? J. Leukoc. Biol. 69, 414–418 (2001).

    CAS  PubMed  Google Scholar 

  35. Caldefie-Chezet, F., Poulin, A. & Vasson, M. P. Leptin regulates functional capacities of polymorphonuclear neutrophils. Free Radic. Res. 37, 809–814 (2003).

    Article  CAS  PubMed  Google Scholar 

  36. Zarkesh-Esfahani, H. et al. Leptin indirectly activates human neutrophils via induction of TNF-α. J. Immunol. 172, 1809–1814 (2004).

    Article  CAS  PubMed  Google Scholar 

  37. Siegmund, B., Lear-Kaul, K. C., Faggioni, R. & Fantuzzi, G. Leptin deficiency, not obesity, protects mice from Con A-induced hepatitis. Eur. J. Immunol. 32, 552–560 (2002).

    Article  CAS  PubMed  Google Scholar 

  38. Zhao, Y., Sun, R., You, L., Gao, C. & Tian, Z. Expression of leptin receptors and response to leptin stimulation of human natural killer cell lines. Biochem. Biophys Res. Commun. 300, 247–252 (2003).

    Article  CAS  PubMed  Google Scholar 

  39. Tian, Z., Sun, R., Wei, H. & Gao, B. Impaired natural killer (NK) cell activity in leptin receptor deficient mice: leptin as a critical regulator in NK cell development and activation. Biochem. Biophys Res. Commun. 298, 297–302 (2002).

    Article  CAS  PubMed  Google Scholar 

  40. Howard, J. K. et al. Leptin protects mice from starvation-induced lymphoid atrophy and increases thymic cellularity in ob/ob mice. J. Clin. Invest. 104, 1051–1059 (1999). The first study of the effects of leptin on thymic cellularity and function.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Lord, G. M., Matarese, G., Howard, J. K. & Lechler, R. I. The bioenergetics of the immune system. Science 292, 855–856 (2001).

    Article  CAS  PubMed  Google Scholar 

  42. Zhang, Y. et al. Peripheral but not central leptin prevents the immunosuppression associated with hypoleptinaemia in rats. J. Endocrinol. 174, 455–461 (2002).

    Article  CAS  PubMed  Google Scholar 

  43. Frauwirth, K. A. et al. The CD28 signaling pathway regulates glucose metabolism. Immunity. 16, 769–777 (2002).

    Article  CAS  PubMed  Google Scholar 

  44. Khaled, A. R. & Durum, S. K. Lymphocide: cytokines and the control of lymphoid homeostasis. Nature Rev. Immunol. 2, 817–830 (2002).

    Article  CAS  Google Scholar 

  45. Berti, L. & Gammeltoft, S. Leptin stimulates glucose uptake in C2C12 muscle cells by activation of ERK2. Mol. Cell. Endocrinol. 157, 121–130 (1999).

    Article  CAS  PubMed  Google Scholar 

  46. Fujita, Y. et al. Leptin inhibits stress-induced apoptosis of T lymphocytes. Clin. Exp. Immunol. 128, 21–26 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Shimabukuro, M., Wang, M. Y., Zhou, Y. T., Newgard, C. B. & Unger, R. H. Protection against lipoapoptosis of β-cells through leptin-dependent maintenance of Bcl-2 expression. Proc. Natl Acad. Sci. USA 95, 9558–9561 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Najib, S. & Sanchez-Margalet, W. Human leptin promotes survival of human circulating blood monocytes prone to apoptosis by activation of p42/44 MAPK pathway. Cell. Immunol. 220, 143–149 (2002).

    Article  CAS  PubMed  Google Scholar 

  49. Farooqi, I. S. et al. Beneficial effects of leptin on obesity, T cell hyporesponsiveness, and neuroendocrine/metabolic dysfunction of human congenital leptin deficiency. J. Clin. Invest. 110, 1093–1103 (2002). The first demonstration that congenitally leptin-deficient individuals have defective CD4+ T-cell function and cytokine abnormalities that can be reversed by leptin replacement.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Faggioni, R. et al. Leptin-deficient (ob/ob) mice are protected from T cell-mediated hepatotoxicity: role of tumor necrosis factor α and IL-18. Proc. Natl Acad. Sci. USA 97, 2367–2372 (2000). This study (together with references 37, 51–53, 56 and 59) shows that leptin-deficient ob/ob mice are resistant to the induction of autoimmunity.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Busso, N. et al. Leptin signaling deficiency impairs humoral and cellular immune responses and attenuates experimental arthritis. J. Immunol. 168, 875–882 (2002).

    Article  CAS  PubMed  Google Scholar 

  52. Matarese, G. et al. Requirement for leptin in the induction and progression of autoimmune encephalomyelitis. J. Immunol. 166, 5909–5916 (2001).

    Article  CAS  PubMed  Google Scholar 

  53. Sanna, V. et al. Leptin surge precedes onset of autoimmune encephalomyelitis and correlates with development of pathogenic T cell responses. J. Clin. Invest. 111, 241–250 (2003). The first report showing that T helper 1 cells can produce leptin and can be found in inflammatory lesions in experimental autoimmune encephalomyelitis.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Lock, C. et al. Gene-microarray analysis of multiple sclerosis lesions yields new targets validated in autoimmune encephalomyelitis. Nature Med. 8, 500–508 (2002).

    Article  CAS  PubMed  Google Scholar 

  55. Batocchi, A. P. et al. Leptin as marker of multiple sclerosis activity in patients treated with interferon-β. J. Neuroimmunol. 139, 150–154 (2003).

    Article  CAS  PubMed  Google Scholar 

  56. Siegmund, B., Lehr, H. A. & Fantuzzi, G. Leptin: a pivotal mediator of intestinal inflammation in mice. Gastroenterology 122, 2011–2025 (2002).

    Article  CAS  PubMed  Google Scholar 

  57. Buyse, M., Sitaraman, S. V., Liu, X., Bado, A. & Merlin, D. Luminal leptin enhances CD147/MCT-1-mediated uptake of butyrate in the human intestinal cell line Caco2-BBE. J. Biol. Chem. 277, 28182–28190 (2002).

    Article  CAS  PubMed  Google Scholar 

  58. Buyse, M. et al. PepT1-mediated epithelial transport of dipeptides and cephalexin is enhanced by luminal leptin in the small intestine. J. Clin. Invest. 108, 1483–1494 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Tarzi, R. M., Cook, T. H., Jackson, I., Pusey, C. D. & Lord, G. M. Leptin-deficient mice are protected from accelerated nephrotoxic nephritis. Am. J. Pathol. 164, 385–390 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Matarese, G. et al. Leptin accelerates autoimmune diabetes in female NOD mice. Diabetes 51, 1356–1361 (2002).

    Article  CAS  PubMed  Google Scholar 

  61. Gaetke, L. M., Oz, H. S., Frederich, R. C. & McClain, C. J. Anti-TNF-α antibody normalizes serum leptin in IL-2 deficient mice. J. Am. Coll. Nutr. 22, 415–420 (2003).

    Article  CAS  PubMed  Google Scholar 

  62. Matarese, G. et al. Leptin potentiates experimental autoimmune encephalomyelitis in SJL female mice and confers susceptibility to males. Eur. J. Immunol. 31, 1324–1332 (2001).

    Article  CAS  PubMed  Google Scholar 

  63. Ozata, M., Ozdemir, I. C. & Licinio, J. Human leptin deficiency caused by a missense mutation: multiple endocrine defects, decreased sympathetic tone, and immune system dysfunction indicates 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. 84, 3686–3690 (1998).

    Article  Google Scholar 

  64. Matarese, G. et al. Increased leptin levels in serum and peritoneal fluid of patients with pelvic endometriosis. J. Clin. Endocrinol. Metab. 85, 2483–2487 (2000).

    CAS  PubMed  Google Scholar 

  65. Uygun, A. et al. Serum leptin levels in patients with nonalcoholic steatohepatitis. Am. J. Gastroenterol. 95, 3584–3589 (2000).

    Article  CAS  PubMed  Google Scholar 

  66. Schols, A. M. et al. Plasma leptin is related to pro-inflammatory status and dietary intake in patients with chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 160, 1220–1226 (1999).

    Article  CAS  PubMed  Google Scholar 

  67. Stein, R. B., Lichtenstein, G. R. & Rombeau, J. L. Nutrition in inflammatory bowel disease. Curr. Opin. Clin. Nutr. Metab. Care 2, 367–371 (1999).

    Article  CAS  PubMed  Google Scholar 

  68. Stenvinkel, P. et al. Increases in serum leptin levels during peritoneal dialysis are associated with inflammation and a decrease in lean body mass. J. Am. Soc. Nephrol. 11, 1303–1309 (2000).

    CAS  PubMed  Google Scholar 

  69. Evereklioglu, C. et al. Serum leptin concentration is increased in patients with Behcet's syndrome and is correlated with disease activity. Br. J. Dermatol. 147, 331–336 (2002).

    Article  CAS  PubMed  Google Scholar 

  70. Sera, N. et al. Thyroid hormones influence serum leptin levels in patients with Graves' diseas during suppression of β-adrenergic receptors. Thyroid 10, 641–646 (2000).

    Article  CAS  PubMed  Google Scholar 

  71. Mazziotti, G. et al. High leptin levels in women developing post-partum thyroiditis. Clin. Endocrinol. 60, 208–213 (2004)

    Article  CAS  Google Scholar 

  72. Ahmed, M. L. et al. Elevated leptin levels are associated with excess gains in fat mass in girls, but not in boys, with type 1 diabetes: longitudinal study during adolescence. J. Clin. Endocrinol. Metab. 86, 1188–1193 (2001).

    Article  CAS  PubMed  Google Scholar 

  73. Bokarewa, M., Bokarew, D., Hultgren, O. & Tarkowski, A. Leptin consumption in the inflamed joints of patients with rheumatoid arthritis. Ann. Rheum. Dis. 62, 952–956 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Anders, H. J., Rihl, M., Heufelder, A., Loch, O. & Schattenkirchner, M. Leptin serum levels are not correlated with disease activity in patients with rheumatoid arthritis. Metabolism 48, 745–748 (1999).

    Article  CAS  PubMed  Google Scholar 

  75. Chalasani, N. et al. Does leptin play a role in the pathogenesis of human nonalcoholic steatohepatitis? Am. J. Gastroenterol. 98, 2771–2776 (2003).

    Article  CAS  PubMed  Google Scholar 

  76. Takabatake, N. et al. Circulating leptin in patients with chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 159, 1215–1219 (1999).

    Article  CAS  PubMed  Google Scholar 

  77. Hoppin, A. G. et al. Serum leptin in children and young adults with inflammatory bowel disease. J. Pediatr. Gastroenterol. Nutr. 26, 500–505 (1998).

    Article  CAS  PubMed  Google Scholar 

  78. Fraser, D. A., Thoen, J., Reseland, J. E., Forre, O. & Kjeldsen-Kragh, J. Decreased CD4+ lymphocyte activation and increased interleukin-4 production in peripheral blood of rheumatoid arthritis patients after acute starvation. Clin. Rheumatol. 18, 394–401 (1999).

    Article  CAS  PubMed  Google Scholar 

  79. Kjeldsen-Kragh, J. et al. Controlled trial of fasting and one year vegetarian diet in rheumatoid arthritis. Lancet 338, 899–902 (1991).

    Article  CAS  PubMed  Google Scholar 

  80. Payne, A. Nutrition and diet in the clinical management of multiple sclerosis. J. Hum. Nutr. Diet. 14, 349–357 (2001).

    Article  CAS  PubMed  Google Scholar 

  81. Beach, R. S., Gershwin, M. E. & Hurley, L. S. Nutritional factors and autoimmunity. III. Zinc deprivation versus restricted food intake in MRL/1 mice — the distinction between interacting dietary influences. J. Immunol. 129, 2686–2692 (1982).

    CAS  PubMed  Google Scholar 

  82. Johnson, B. C., Gajjar, A., Kubo, C. & Good, R. A. Calories versus protein in onset of renal disease in NZB × NZW mice. Proc. Natl Acad. Sci. USA 83, 5659–5662 (1986).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Mizutani, H. et al. Calorie restriction prevents the occlusive coronary vascular disease of autoimmune (NZW × BXSB) F1 mice. Proc. Natl Acad. Sci. USA 91, 4402–4406 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Chandrasekar, B. et al. Effects of calorie restriction of transforming growth factor-β1 and proinflammatory cytokines in murine Sjogren's syndrome. Clin. Immunol. Immunopathol. 76, 291–296 (1995).

    Article  CAS  PubMed  Google Scholar 

  85. Steinman, L., Conlon, P., Maki, R. & Foster, A. The intricate interplay among body weight, stress, and the immune response to friend or foe. J. Clin. Invest. 111, 183–185 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Kuchroo, V. K. & Nicholson, L. B. Fast and feel good? Nature 422, 27–28 (2003).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  88. Sanchez-Margalet, V. & Marin-Romero, C. Human leptin signaling in human peripheral blood mononuclear cells: activation of the JAK–STAT pathway. Cell. Immunol. 211, 30–36 (2001).

    Article  CAS  PubMed  Google Scholar 

  89. Van den Brink, G. R. et al. Leptin signaling in human peripheral blood mononuclear cells, activation of p38 and p42/44 mitogen-activated protein (MAP) kinase and p70 S6 kinase. Mol. Cell. Biol. Res. Commun. 4, 144–150 (2000).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by the Fondazione Italiana Sclerosi Multipla (FISM) and Comitato Trenta Ore per la Vita (Mediaset), and the Arthritis National Research and Lupus Foundations. This work is dedicated to the memory of A. Di Tuoro.

Author information

Authors and Affiliations

  1. Department of Medicine, Autoimmunity and Tolerance Laboratory, University of California Los Angeles, 1000 Veteran Avenue 32-59, Los Angeles, 90095-1670, California, USA

    Antonio La Cava

  2. Dipartimento di Biologia e Patologia Cellulare e Molecolare, Gruppo di Immuno Endocrinologia, Istituto di Endocrinologia ed Oncologia Sperimentale, Consiglio Nazionale delle Ricerche (IEOS-CNR) c/o Cattedra di Immunologia, Università di Napoli 'Federico II', via S. Pansini, Napoli, 5-80131, Italy

    Giuseppe Matarese

Authors
  1. Antonio La Cava
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Giuseppe Matarese
    View author publications

    You can also search for this author in PubMed Google Scholar

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Related links

Related links

DATABASES

LocusLink

ACTH

CCL3

CD49B

COX2

CRH

CRP

CXCL2

G-CSF

GLUT1

GLUT4

ICAM1

IFN-γ

IL-1

IL-6

IL-18

ob

OBR

OSM

STAT3

TNF

Glossary

HYPOTHALAMO–PITUITARY–ADRENAL (HPA) AXIS

The neuroendocrine and immune systems communicate bidirectionally through shared ligands and receptors. Factors secreted by the hypothalamus, the pituitary and adrenal glands, such as corticotrophin-releasing hormone, adrenocorticotropic hormone and glucocorticoids, can influence both immune and neuroendocrine responses. Cytokines secreted by immune cells, such as interleukin-1 (IL-1), IL-6, tumour-necrosis factor and interferon-γ, also influence the HPA axis.

GLUCOCORTICOIDS

A series of steroids that influence glucose metabolism, lipolysis and protein synthesis. In humans, the most abundant glucocorticoid is cortisol (also known as hydrocortisone). Secreted with circadian rhythm by the adrenal-gland cortex, glucocorticoids mediate their effects by binding to specific cytosolic receptors. Immunologically, glucocorticoids inhibit the mobilization and function of T and B cells, as well as the secretion of inflammatory mediators. Also, glucocorticoids can induce the apoptosis of developing thymocytes. Natural and synthetic glucocorticoids (that is, prednisolone and dexamethasone) are often used in therapy as anti-inflammatory and immunosuppressive agents.

C-REACTIVE PROTEIN

(CRP). An important acute-phase reactant secreted during inflammation and sepsis. It is part of the collectin family — a group of soluble proteins with an amino terminus similar to collagen. CRP can activate both the classical and alternative pathways of complement activation after binding one of its ligands — Fc-γ receptor I on immune cells or carbohydrates of Streptococcus pneumoniae.

OMENTUM

A fold of the peritoneum that extends downwards from the greater curvature of the stomach to lie anteriorly in the peritoneal cavity. It folds back on itself and is adherent to the transverse colon as it crosses the pancreas. The anterior and posterior leaves usually fuse. It often contains an abundant accumulation of adipose tissue and lymph nodes in strict anatomical contiguity.

MIXED LYMPHOCYTE REACTION

(MLR). When lymphocytes from two unrelated individuals are cultured together, the T cells of one donor proliferate in response to the allogeneic MHC molecules on the cells of the other donor. The MLR is used to test for histocompatibility.

DELAYED-TYPE HYPERSENSITIVITY

(DTH). A form of cell-mediated immunity elicited by antigen in the skin and mediated by CD4+ T helper 1 cells. It is called 'delayed-type' because the reaction appears hours to days after antigen is injected.

ANTIGEN-INDUCED ARTHRITIS

(AIA). An inflammatory disease of the joints that develops in susceptible mice immunized with methylated bovine serum albumin into the knees in immunogenic adjuvant. It is considered to be a model of inflammatory arthritis.

EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS

(EAE). An inflammatory disease of the central nervous system that develops in susceptible mice immunized with neural antigens in immunogenic adjuvant. It is considered to be a model of human multiple sclerosis.

HYPERPHAGIA

A condition of excessive eating beyond normal hunger.

HYPOTHALAMIC HYPOGONADISM

A condition of decreased functional activity of the gonads, resulting in retardation of puberty and/or reproductive insufficiency. It is due to disorders of the hypothalamus or of the pituitary gland.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cava, A., Matarese, G. The weight of leptin in immunity. Nat Rev Immunol 4, 371–379 (2004). https://doi.org/10.1038/nri1350

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nri1350

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing