Table of Contents
Journal of Allergy
Volume 2013 (2013), Article ID 785835, 15 pages
http://dx.doi.org/10.1155/2013/785835
Review Article

Adiponectin, Leptin, and Resistin in Asthma: Basic Mechanisms through Population Studies

1School of Medicine, Department of Medicine, University of New Mexico, MSC 10 5550, Albuquerque, NM 87131, USA
2Department of Environmental Health, Molecular and Integrative Physiological Sciences Program, Harvard School of Public Health, 665 Huntington Avenue, Building I, Room 307, Boston, MA 02115, USA

Received 28 February 2013; Revised 3 September 2013; Accepted 5 September 2013

Academic Editor: Balaram Ghosh

Copyright © 2013 Akshay Sood and Stephanie A. Shore. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. C. S. Farah and C. M. Salome, “Asthma and obesity: a known association but unknown mechanism,” Respirology, vol. 17, no. 3, pp. 412–421, 2012. View at Publisher · View at Google Scholar · View at Scopus
  2. A. R. Stream and E. R. Sutherland, “Obesity and asthma disease phenotypes,” Current Opinion in Allergy and Clinical Immunology, vol. 12, no. 1, pp. 76–81, 2012. View at Publisher · View at Google Scholar · View at Scopus
  3. C. Papoutsakis, K. N. Priftis, M. Drakouli et al., “Childhood overweight/obesity and asthma: is there a link? A systematic review of recent epidemiologic evidence,” Journal of the Academy of Nutrition and Dietetics, vol. 113, no. 1, pp. 77–105, 2013. View at Google Scholar
  4. P. Trayhurn, “Hypoxia and adipose tissue function and dysfunction in obesity,” Physiological Reviews, vol. 93, no. 1, pp. 1–21, 2013. View at Google Scholar
  5. A. R. Johnson, J. J. Milner, and L. Makowski, “The inflammation highway: metabolism accelerates inflammatory traffic in obesity,” Immunological Reviews, vol. 249, no. 1, pp. 218–238, 2012. View at Google Scholar
  6. K. M. Ajuwon and M. E. Spurlock, “Adiponectin inhibits LPS-induced NF-κB activation and IL-6 production and increases PPARγ2 expression in adipocytes,” American Journal of Physiology—Regulatory Integrative and Comparative Physiology, vol. 288, no. 5, pp. R1220–R1225, 2005. View at Publisher · View at Google Scholar · View at Scopus
  7. T. Masaki, S. Chiba, H. Tatsukawa et al., “Adiponectin protects LPS-induced liver injury through modulation of TNF-α in KK-Ay obese mice,” Hepatology, vol. 40, no. 1, pp. 177–184, 2004. View at Publisher · View at Google Scholar · View at Scopus
  8. M. C. Wulster-Radcliffe, K. M. Ajuwon, J. Wang, J. A. Christian, and M. E. Spurlock, “Adiponectin differentially regulates cytokines in porcine macrophages,” Biochemical and Biophysical Research Communications, vol. 316, no. 3, pp. 924–929, 2004. View at Publisher · View at Google Scholar · View at Scopus
  9. M. Kumada, S. Kihara, N. Ouchi et al., “Adiponectin specifically increased tissue inhibitor of metalloproteinase-1 through interleukin-10 expression in human macrophages,” Circulation, vol. 109, no. 17, pp. 2046–2049, 2004. View at Publisher · View at Google Scholar · View at Scopus
  10. A. M. Wolf, D. Wolf, H. Rumpold, B. Enrich, and H. Tilg, “Adiponectin induces the anti-inflammatory cytokines IL-10 and IL-1RA in human leukocytes,” Biochemical and Biophysical Research Communications, vol. 323, no. 2, pp. 630–635, 2004. View at Publisher · View at Google Scholar · View at Scopus
  11. A. Ehling, A. Schäffler, H. Herfarth et al., “The potential of adiponectin in driving arthritis,” Journal of Immunology, vol. 176, no. 7, pp. 4468–4478, 2006. View at Google Scholar · View at Scopus
  12. F. Haugen and C. A. Drevon, “Activation of nuclear factor-κB by high molecular weight and globular adiponectin,” Endocrinology, vol. 148, no. 11, pp. 5478–5486, 2007. View at Publisher · View at Google Scholar · View at Scopus
  13. N. Ouchi, S. Kihara, Y. Arita et al., “Novel modulator for endothelial adhesion molecules: adipocyte-derived plasma protein adiponectin,” Circulation, vol. 100, no. 25, pp. 2473–2476, 1999. View at Google Scholar · View at Scopus
  14. M. W. Steffes, M. D. Gross, P. J. Schreiner et al., “Serum adiponectin in young adults—interactions with central adiposity, circulating levels of glucose, and insulin resistance: The CARDIA Study,” Annals of Epidemiology, vol. 14, no. 7, pp. 492–498, 2004. View at Publisher · View at Google Scholar · View at Scopus
  15. Y. Arita, S. Kihara, N. Ouchi et al., “Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity,” Biochemical and Biophysical Research Communications, vol. 257, no. 1, pp. 79–83, 1999. View at Publisher · View at Google Scholar · View at Scopus
  16. S. Cinti, G. Mitchell, G. Barbatelli et al., “Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans,” Journal of Lipid Research, vol. 46, no. 11, pp. 2347–2355, 2005. View at Publisher · View at Google Scholar · View at Scopus
  17. J. M. Bruun, A. S. Lihn, C. Verdich et al., “Regulation of adiponectin by adipose tissue-derived cytokines: In vivo and in vitro investigations in humans,” American Journal of Physiology—Endocrinology and Metabolism, vol. 285, no. 3, pp. E527–E533, 2003. View at Google Scholar · View at Scopus
  18. P. E. Scherer, S. Williams, M. Fogliano, G. Baldini, and H. F. Lodish, “A novel serum protein similar to C1q, produced exclusively in adipocytes,” The Journal of Biological Chemistry, vol. 270, no. 45, pp. 26746–26749, 1995. View at Publisher · View at Google Scholar · View at Scopus
  19. M. J. Jeon, J. Leem, M. Seok Ko et al., “Mitochondrial dysfunction and activation of iNOS are responsible for the palmitate-induced decrease in adiponectin synthesis in 3T3L1 adipocytes,” Experimental & Molecular Medicine, vol. 44, no. 9, pp. 562–570, 2012. View at Google Scholar
  20. U. B. Pajvani, X. Du, T. P. Combs et al., “Structure-function studies of the adipocyte-secreted hormone Acrp30/adiponectin: implications for metabolic regulation and bioactivity,” The Journal of Biological Chemistry, vol. 278, no. 11, pp. 9073–9085, 2003. View at Publisher · View at Google Scholar · View at Scopus
  21. A. Böttner, J. Kratzsch, G. Müller et al., “Gender differences of adiponectin levels develop during the progression of puberty and are related to serum androgen levels,” Journal of Clinical Endocrinology and Metabolism, vol. 89, no. 8, pp. 4053–4061, 2004. View at Publisher · View at Google Scholar · View at Scopus
  22. S. Kaser, T. Tatarczyk, A. Stadlmayr et al., “Effect of obesity and insulin sensitivity on adiponectin isoform distribution,” European Journal of Clinical Investigation, vol. 38, no. 11, pp. 827–834, 2008. View at Publisher · View at Google Scholar · View at Scopus
  23. A. Sood, J. Seagrave, G. Herbert, M. Harkins, C. Qualls, and M. Schuyler, “Asthma is associated with lower adiponectin concentrations in sputum than controls,” American Journal of Respiratory and Critical Care Medicine, vol. 185, 2012, abstract A6502. View at Google Scholar
  24. M. Zhu, C. Hug, D. I. Kasahara et al., “Impact of adiponectin deficiency on pulmonary responses to acute ozone exposure in mice,” American Journal of Respiratory Cell and Molecular Biology, vol. 43, no. 4, pp. 487–497, 2010. View at Google Scholar
  25. F. Holguin, M. Rojas, L. A. Brown, and A. M. Fitzpatrick, “Airway and plasma leptin and adiponectin in lean and obese asthmatics and controls,” Journal of Asthma, vol. 48, no. 3, pp. 217–223, 2011. View at Publisher · View at Google Scholar · View at Scopus
  26. P. W. Peake, A. D. Kriketos, L. V. Campbell, Y. Shen, and J. A. Charlesworth, “The metabolism of isoforms of human adiponectin: studies in human subjects and in experimental animals,” European Journal of Endocrinology, vol. 153, no. 3, pp. 409–417, 2005. View at Publisher · View at Google Scholar · View at Scopus
  27. P. Garcia and A. Sood, “Adiponectin in pulmonary disease and critically ill patients,” Current Medicinal Chemistry, vol. 19, no. 32, pp. 5493–5500, 2012. View at Google Scholar
  28. K. Hara, M. Horikoshi, T. Yamauchi et al., “Measurement of the high-molecular weight form of adiponectin in plasma is useful for the prediction of insulin resistance and metabolic syndrome,” Diabetes Care, vol. 29, no. 6, pp. 1357–1362, 2006. View at Publisher · View at Google Scholar · View at Scopus
  29. U. B. Pajvani, M. Hawkins, T. P. Combs et al., “Complex distribution, not absolute amount of adiponectin, correlates with thiazolidinedione-mediated improvement in insulin sensitivity,” The Journal of Biological Chemistry, vol. 279, no. 13, pp. 12152–12162, 2004. View at Publisher · View at Google Scholar · View at Scopus
  30. H. J. McCourt, S. J. Hunter, C. R. Cardwell et al., “Adiponectin multimers, body weight and markers of cardiovascular risk in adolescence: Northern Ireland Young Hearts Project,” International Journal of Obesity, vol. 37, no. 9, pp. 1247–1253, 2013. View at Publisher · View at Google Scholar
  31. M. Miller, J. Y. Cho, A. Pham, J. Ramsdell, and D. H. Broide, “Adiponectin and functional adiponectin receptor 1 are expressed by airway epithelial cells in chronic obstructive pulmonary disease,” Journal of Immunology, vol. 182, no. 1, pp. 684–691, 2009. View at Google Scholar · View at Scopus
  32. X. L. Zhu, X. Q. Qin, Y. Xiang, Y. R. Tan, X. P. Qu, and H. J. Liu, “Adipokine adiponectin is a potential protector to human bronchial epithelial cell for regulating proliferation, wound repair and apoptosis: comparison with leptin and resistin,” Peptides, vol. 40, pp. 34–41, 2013. View at Publisher · View at Google Scholar
  33. J. H. Shin, J. H. Kim, W. Y. Lee, and J. Y. Shim, “The expression of adiponectin receptors and the effects of adiponectin and leptin on airway smooth muscle cells,” Yonsei Medical Journal, vol. 49, no. 5, pp. 804–810, 2008. View at Publisher · View at Google Scholar · View at Scopus
  34. J. M. Konter, J. L. Parker, E. Baez et al., “Adiponectin attenuates lipopolysaccharide-induced acute lung injury through suppression of endothelial cell activation,” Journal of Immunology, vol. 188, no. 2, pp. 854–863, 2012. View at Publisher · View at Google Scholar · View at Scopus
  35. M. Weng, M. J. Raher, P. Leyton et al., “Adiponectin decreases pulmonary arterial remodeling in murine models of pulmonary hypertension,” American Journal of Respiratory Cell and Molecular Biology, vol. 45, no. 2, pp. 340–347, 2011. View at Publisher · View at Google Scholar · View at Scopus
  36. O. Sideleva, B. T. Suratt, K. E. Black et al., “Obesity and asthma: an inflammatory disease of adipose tissue not the airway,” American Journal of Respiratory and Critical Care Medicine, vol. 186, no. 7, pp. 598–605, 2012. View at Google Scholar
  37. T. Kadowaki, T. Yamauchi, N. Kubota, K. Hara, K. Ueki, and K. Tobe, “Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome,” The Journal of Clinical Investigation, vol. 116, no. 7, pp. 1784–1792, 2006. View at Publisher · View at Google Scholar · View at Scopus
  38. T. Yamauchi, Y. Nio, T. Maki et al., “Targeted disruption of AdipoR1 and AdipoR2 causes abrogation of adiponectin binding and metabolic actions,” Nature Medicine, vol. 13, no. 3, pp. 332–339, 2007. View at Publisher · View at Google Scholar · View at Scopus
  39. W. L. Holland, R. A. Miller, Z. V. Wang et al., “Receptor-mediated activation of ceramidase activity initiates the pleiotropic actions of adiponectin,” Nature Medicine, vol. 17, no. 1, pp. 55–63, 2011. View at Publisher · View at Google Scholar · View at Scopus
  40. R. Summer, F. F. Little, N. Ouchi et al., “Alveolar macrophage activation and an emphysema-like phenotype in adiponectin-deficient mice,” American Journal of Physiology—Lung Cellular and Molecular Physiology, vol. 294, no. 6, pp. L1035–L1042, 2008. View at Publisher · View at Google Scholar · View at Scopus
  41. L. W. Hebbard, M. Garlatti, L. J. T. Young, R. D. Cardiff, R. G. Oshima, and B. Ranscht, “T-cadherin supports angiogenesis and adiponectin association with the vasculature in a mouse mammary tumor model,” Cancer Research, vol. 68, no. 5, pp. 1407–1416, 2008. View at Publisher · View at Google Scholar · View at Scopus
  42. C. Hug, J. Wang, N. S. Ahmad, J. S. Bogan, T.-S. Tsao, and H. F. Lodish, “T-cadherin is a receptor for hexameric and high-molecular-weight forms of Acrp30/adiponectin,” Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 28, pp. 10308–10313, 2004. View at Publisher · View at Google Scholar · View at Scopus
  43. A. S. Williams, D. I. Kasahara, N. G. Verbout et al., “Role of the adiponectin binding protein, T-cadherin (Cdh13), in allergic airways responses in mice,” PLoS One, vol. 7, no. 7, Article ID e41088, 2012. View at Google Scholar
  44. D. I. Kasahara, H. Y. Kim, A. S. Williams et al., “Pulmonary inflammation induced by subacute ozone is augmented in adiponectin-deficient mice: Role of IL-17A,” Journal of Immunology, vol. 188, no. 9, pp. 4558–4567, 2012. View at Publisher · View at Google Scholar · View at Scopus
  45. P. E. Scherer, “Adipose tissue: from lipid storage compartment to endocrine organ,” Diabetes, vol. 55, no. 6, pp. 1537–1545, 2006. View at Publisher · View at Google Scholar · View at Scopus
  46. S. A. Shore, R. D. Terry, L. Flynt, A. Xu, and C. Hug, “Adiponectin attenuates allergen-induced airway inflammation and hyperresponsiveness in mice,” Journal of Allergy and Clinical Immunology, vol. 118, no. 2, pp. 389–395, 2006. View at Publisher · View at Google Scholar · View at Scopus
  47. L. I. Ionescu, R. S. Alphonse, N. Arizmendi et al., “Airway delivery of soluble factors from plastic-adherent bone marrow cells prevents murine asthma,” American Journal of Respiratory Cell and Molecular Biology, vol. 46, no. 2, pp. 207–216, 2012. View at Publisher · View at Google Scholar · View at Scopus
  48. M. Fuerst, C. G. Taylor, B. Wright, L. Tworek, and P. Zahradka, “Inhibition of smooth muscle cell proliferation by adiponectin requires proteolytic conversion to its globular form,” Journal of Endocrinology, vol. 215, no. 1, pp. 107–117, 2012. View at Google Scholar
  49. A. Sood, E. Dominic, C. Qualls et al., “Serum adiponectin is associated with adverse outcomes of asthma in men but not in women,” Frontiers in Pharmacology, vol. 2, article 55, 2011. View at Google Scholar
  50. B. D. Medoff, Y. Okamoto, P. Leyton et al., “Adiponectin deficiency increases allergic airway inflammation and pulmonary vascular remodeling,” American Journal of Respiratory Cell and Molecular Biology, vol. 41, no. 4, pp. 397–406, 2009. View at Publisher · View at Google Scholar · View at Scopus
  51. K. Ohashi, J. L. Parker, N. Ouchi et al., “Adiponectin promotes macrophage polarization toward an anti-inflammatory phenotype,” The Journal of Biological Chemistry, vol. 285, no. 9, pp. 6153–6160, 2010. View at Publisher · View at Google Scholar · View at Scopus
  52. X. Cheng, E. J. Folco, K. Shimizu, and P. Libby, “Adiponectin induces pro-inflammatory programs in human macrophages and CD4+ T cells,” The Journal of Biological Chemistry, vol. 287, no. 44, pp. 36896–36904, 2012. View at Google Scholar
  53. M. Y. Jung, H. S. Kim, H. J. Hong, B. S. Youn, and T. S. Kim, “Adiponectin induces dendritic cell activation via PLCgamma/JNK/NF-kappaB pathways, leading to Th1 and Th17 polarization,” Journal of Immunology, vol. 188, no. 6, pp. 2592–2601, 2012. View at Google Scholar
  54. S. Wilk, C. Scheibenbogen, S. Bauer et al., “Adiponectin is a negative regulator of antigen-activated T cells,” European Journal of Immunology, vol. 41, no. 8, pp. 2323–2332, 2011. View at Google Scholar
  55. K. W. Kim, Y. H. Shin, K. E. Lee, E. S. Kim, M. H. Sohn, and K.-E. Kim, “Relationship between adipokines and manifestations of childhood asthma,” Pediatric Allergy and Immunology, vol. 19, no. 6, pp. 535–540, 2008. View at Publisher · View at Google Scholar · View at Scopus
  56. H.-S. Baek, Y.-D. Kim, J.-H. Shin, J.-H. Kim, J.-W. Oh, and H.-B. Lee, “Serum leptin and adiponectin levels correlate with exercise-induced bronchoconstriction in children with asthma,” Annals of Allergy, Asthma and Immunology, vol. 107, no. 1, pp. 14–21, 2011. View at Publisher · View at Google Scholar · View at Scopus
  57. N. Guler, E. Kirerleri, U. Ones, Z. Tamay, N. Salmayenli, and F. Darendeliler, “Leptin: does it have any role in childhood asthma?” Journal of Allergy and Clinical Immunology, vol. 114, no. 2, pp. 254–259, 2004. View at Publisher · View at Google Scholar · View at Scopus
  58. X.-M. Mai, M. F. Böttcher, and I. Leijon, “Leptin and asthma in overweight children at 12 years of age,” Pediatric Allergy and Immunology, vol. 15, no. 6, pp. 523–530, 2004. View at Publisher · View at Google Scholar · View at Scopus
  59. F. Gurkan, Y. Atamer, A. Ece, Y. Kocyigit, H. Tuzun, and N. Mete, “Serum leptin levels in asthmatic children treated with an inhaled corticosteroid,” Annals of Allergy, Asthma and Immunology, vol. 93, no. 3, pp. 277–280, 2004. View at Google Scholar · View at Scopus
  60. F. Gurkan, Y. Atamer, A. Ece, Y. Kocyigit, H. Tuzun, and N. Mete, “Serum leptin levels in asthmatic children treated with an inhaled corticosteroid,” Annals of Allergy, Asthma and Immunology, vol. 93, no. 3, pp. 277–280, 2004. View at Google Scholar · View at Scopus
  61. A. Tanju, F. Cekmez, S. Aydinoz, F. Karademir, S. Suleymanoglu, and I. Gocmen, “Association between clinical severity of childhood asthma and serum leptin levels,” Indian Journal of Pediatrics, vol. 78, no. 3, pp. 291–295, 2011. View at Publisher · View at Google Scholar · View at Scopus
  62. M. Kattan, R. Kumar, G. R. Bloomberg et al., “Asthma control, adiposity, and adipokines among inner-city adolescents,” Journal of Allergy and Clinical Immunology, vol. 125, no. 3, pp. 584–592, 2010. View at Publisher · View at Google Scholar · View at Scopus
  63. A. Sood, X. Cui, C. Quails et al., “Association between asthma and serum adiponectin concentration in women,” Thorax, vol. 63, no. 10, pp. 877–882, 2008. View at Publisher · View at Google Scholar · View at Scopus
  64. T. Jartti, L. Saarikoski, L. Jartti et al., “Obesity, adipokines and asthma,” Allergy, vol. 64, no. 5, pp. 770–777, 2009. View at Publisher · View at Google Scholar · View at Scopus
  65. T. J. T. Sutherland, M. R. Sears, C. R. McLachlan, R. Poulton, and R. J. Hancox, “Leptin, adiponectin, and asthma: findings from a population-based cohort study,” Annals of Allergy, Asthma and Immunology, vol. 103, no. 2, pp. 101–107, 2009. View at Publisher · View at Google Scholar · View at Scopus
  66. A. Sood, E. S. Ford, and C. A. Camargo Jr., “Association between leptin and asthma in adults,” Thorax, vol. 61, no. 4, pp. 300–305, 2006. View at Publisher · View at Google Scholar · View at Scopus
  67. G. Nagel, W. Koenig, K. Rapp, M. Wabitsch, I. Zoellner, and S. K. Weiland, “Associations of adipokines with asthma, rhinoconjunctivitis, and eczema in German schoolchildren,” Pediatric Allergy and Immunology, vol. 20, no. 1, pp. 81–88, 2009. View at Publisher · View at Google Scholar · View at Scopus
  68. P. L. da Silva, M. T. De Mello, N. C. Cheik et al., “Interdisciplinary therapy improves biomarkers profile and lung function in asthmatic obese adolescents,” Pediatric Pulmonology, vol. 47, no. 1, pp. 8–17, 2012. View at Publisher · View at Google Scholar · View at Scopus
  69. A. Sood, C. Qualls, M. Schuyler et al., “Low serum adiponectin predicts future risk for asthma in women,” American Journal of Respiratory and Critical Care Medicine, vol. 186, no. 1, pp. 41–47, 2012. View at Google Scholar
  70. A. Tsaroucha, Z. Daniil, F. Malli et al., “Leptin, adiponectin, and ghrelin levels in female patients with asthma during stable and exacerbation periods,” Journal of Asthma, vol. 50, no. 2, pp. 188–197, 2013. View at Google Scholar
  71. A. E. Dixon, S. E. Johnson, L. V. Griffes et al., “Relationship of adipokines with immune response and lung function in obese asthmatic and non-asthmatic women,” Journal of Asthma, vol. 48, no. 8, pp. 811–817, 2011. View at Publisher · View at Google Scholar · View at Scopus
  72. A.-S. Jang, T.-H. Kim, J.-S. Park et al., “Association of serum leptin and adiponectin with obesity in asthmatics,” Journal of Asthma, vol. 46, no. 1, pp. 59–63, 2009. View at Publisher · View at Google Scholar · View at Scopus
  73. Y. Wu, Y. Li, E. M. Lange et al., “Genome-wide association study for adiponectin levels in filipino women identifies CDH13 and a novel uncommon haplotype at KNG1-ADIPOQ,” Human Molecular Genetics, vol. 19, no. 24, Article ID ddq423, pp. 4955–4964, 2010. View at Publisher · View at Google Scholar · View at Scopus
  74. S. H. Jee, J. W. Sull, J. E. Lee et al., “Adiponectin concentrations: a genome-wide association study,” American Journal of Human Genetics, vol. 87, no. 4, pp. 545–552, 2010. View at Google Scholar
  75. A. Sood, C. Quails, J. Seagrave et al., “Effect of specific allergen inhalation on serum adiponectin in human asthma,” Chest, vol. 135, no. 2, pp. 287–294, 2009. View at Publisher · View at Google Scholar · View at Scopus
  76. H. I. Yoon, Y. Li, S. F. Man et al., “The complex relationship of serum adiponectin to COPD outcomes COPD and adiponectin,” Chest, vol. 142, no. 4, pp. 893–899, 2012. View at Google Scholar
  77. S. Krdar, M. Serter, E. Ceylan, A. G. Şener, T. Kavak, and F. Karadaǧ, “Adiponectin as a biomarker of systemic inflammatory response in smoker patients with stable and exacerbation phases of chronic obstructive pulmonary disease,” Scandinavian Journal of Clinical and Laboratory Investigation, vol. 69, no. 2, pp. 219–224, 2009. View at Publisher · View at Google Scholar · View at Scopus
  78. K. Tomoda, M. Yoshikawa, T. Itoh et al., “Elevated circulating plasma adiponectin in underweight patients with COPD,” Chest, vol. 132, no. 1, pp. 135–140, 2007. View at Publisher · View at Google Scholar · View at Scopus
  79. K. H. Chan, S. C. Yeung, T. J. Yao et al., “Elevated plasma adiponectin levels in patients with chronic obstructive pulmonary disease,” International Journal of Tuberculosis and Lung Disease, vol. 14, no. 9, pp. 1193–1200, 2010. View at Google Scholar
  80. Y. Zhang, R. Proenca, M. Maffei, M. Barone, L. Leopold, and J. M. Friedman, “Positional cloning of the mouse obese gene and its human homologue,” Nature, vol. 372, no. 6505, pp. 425–432, 1994. View at Publisher · View at Google Scholar · View at Scopus
  81. M. Mapfei, J. Halaas, E. Ravussin et al., “Leptin levels in human and rodent: measurement of plasma leptin and ob RNA in obese and weight-reduced subjects,” Nature Medicine, vol. 1, no. 11, pp. 1155–1161, 1995. View at Google Scholar · View at Scopus
  82. A. Hsu, D. M. Aronoff, J. Phipps, D. Goel, and P. Mancuso, “Leptin improves pulmonary bacterial clearance and survival in ob/ob mice during pneumococcal pneumonia,” Clinical and Experimental Immunology, vol. 150, no. 2, pp. 332–339, 2007. View at Publisher · View at Google Scholar · View at Scopus
  83. P. Mancuso, A. Gottschalk, S. M. Phare, M. Peters-Golden, N. W. Lukacs, and G. B. Huffnagle, “Leptin-deficient mice exhibit impaired host defense in Gram-negative pneumonia,” Journal of Immunology, vol. 168, no. 8, pp. 4018–4024, 2002. View at Google Scholar · View at Scopus
  84. C. A. Mastronardi, A. Walczewska, W. H. Yu, S. Karanth, A. F. Parlow, and S. M. McCann, “The possible role of prolactin in the circadian rhythm of leptin secretion in male rats,” Proceedings of the Society for Experimental Biology and Medicine, vol. 224, no. 3, pp. 152–158, 2000. View at Google Scholar · View at Scopus
  85. W. F. Blum, P. Englaro, S. Hanitsch et al., “Plasma leptin levels in healthy children and adolescents: dependence on body mass index, body fat mass, gender, pubertal stage, and testosterone,” Journal of Clinical Endocrinology and Metabolism, vol. 82, no. 9, pp. 2904–2910, 1997. View at Publisher · View at Google Scholar · View at Scopus
  86. G. Perseghin, P. Scifo, E. Pagliato et al., “Gender factors affect fatty acids-induced insulin resistance in nonobese humans: effects of oral steroidal contraception,” Journal of Clinical Endocrinology and Metabolism, vol. 86, no. 7, pp. 3188–3196, 2001. View at Publisher · View at Google Scholar · View at Scopus
  87. M. F. Saad, S. Damani, R. L. Gingerich et al., “Sexual dimorphism in plasma leptin concentration,” Journal of Clinical Endocrinology and Metabolism, vol. 82, no. 2, pp. 579–584, 1997. View at Google Scholar
  88. J. Licinio, A. B. Negrão, C. Mantzoros et al., “Sex differences in circulating human leptin pulse amplitude: clinical implications,” Journal of Clinical Endocrinology and Metabolism, vol. 83, no. 11, pp. 4140–4147, 1998. View at Google Scholar · View at Scopus
  89. A. Kennedy, T. W. Gettys, P. Watson et al., “The metabolic significance of leptin in humans: gender-based differences in relationship to adiposity, insulin sensitivity, and energy expenditure,” Journal of Clinical Endocrinology and Metabolism, vol. 82, no. 4, pp. 1293–1300, 1997. View at Publisher · View at Google Scholar · View at Scopus
  90. J. M. H. Elbers, H. Asscheman, J. C. Seidell, M. Frölich, A. E. Meinders, and L. J. G. Gooren, “Reversal of the sex difference in serum leptin levels upon cross-sex hormone administration in transsexuals,” Journal of Clinical Endocrinology and Metabolism, vol. 82, no. 10, pp. 3267–3270, 1997. View at Publisher · View at Google Scholar · View at Scopus
  91. F. Linnqvist, P. Arner, L. Nordfors, and M. Schalling, “Overexpression of the obese (ob) gene in adipose tissue of human obese subjects,” Nature Medicine, vol. 1, no. 9, pp. 950–953, 1995. View at Google Scholar · View at Scopus
  92. G. Wiesner, M. Vaz, G. Collier et al., “Leptin is released from the human brain: Influence of adiposity and gender,” Journal of Clinical Endocrinology and Metabolism, vol. 84, no. 7, pp. 2270–2274, 1999. View at Google Scholar · View at Scopus
  93. J. H. J. Vernooy, N. E. A. Drummen, R. J. Van Suylen et al., “Enhanced pulmonary leptin expression in patients with severe COPD and asymptomatic smokers,” Thorax, vol. 64, no. 1, pp. 26–32, 2009. View at Publisher · View at Google Scholar · View at Scopus
  94. A. Bruno, E. Pace, P. Chanez et al., “Leptin and leptin receptor expression in asthma,” Journal of Allergy and Clinical Immunology, vol. 124, no. 2, pp. 230.e4–237.e4, 2009. View at Publisher · View at Google Scholar · View at Scopus
  95. L. A. Tartaglia, “The leptin receptor,” The Journal of Biological Chemistry, vol. 272, no. 10, pp. 6093–6096, 1997. View at Google Scholar · View at Scopus
  96. J. Wauman and J. Tavernier, “Leptin receptor signaling: pathways to leptin resistance,” Frontiers in Bioscience, vol. 16, no. 7, pp. 2771–2793, 2011. View at Publisher · View at Google Scholar · View at Scopus
  97. B. Lollmann, S. Grüninger, A. Stricker-Krongrad, and M. Chiesi, “Detection and quantification of the leptin receptor splice variants Ob-Ra, b, and, e in different mouse tissues,” Biochemical and Biophysical Research Communications, vol. 238, no. 2, pp. 648–652, 1997. View at Google Scholar
  98. T. Tsuchiya, H. Shimizu, T. Horie, and M. Mori, “Expression of leptin receptor in lung: Leptin as a growth factor,” European Journal of Pharmacology, vol. 365, no. 2-3, pp. 273–279, 1999. View at Publisher · View at Google Scholar · View at Scopus
  99. P. Nair, K. Radford, A. Fanat et al., “The effects of leptin on airway smooth muscle responses,” American Journal of Respiratory Cell and Molecular Biology, vol. 39, no. 4, pp. 475–481, 2008. View at Google Scholar
  100. S. A. Shore, Y. M. Rivera-Sanchez, I. N. Schwartzman, and R. A. Johnston, “Responses to ozone are increased in obese mice,” Journal of Applied Physiology, vol. 95, no. 3, pp. 938–945, 2003. View at Google Scholar · View at Scopus
  101. F. L. Lu, R. A. Johnston, L. Flynt et al., “Increased pulmonary responses to acute ozone exposure in obese db/db mice,” American Journal of Physiology—Lung Cellular and Molecular Physiology, vol. 290, no. 5, pp. L856–L865, 2006. View at Publisher · View at Google Scholar · View at Scopus
  102. F. Carbone, C. La Rocca, and G. Matarese, “Immunological functions of leptin and adiponectin,” Biochimie, vol. 94, no. 10, pp. 2082–2088, 2012. View at Google Scholar
  103. P. Mancuso, C. Canetti, A. Gottschalk, P. K. Tithof, and M. Peters-Golden, “Leptin augments alveolar macrophage leukotriene synthesis by increasing phospholipase activity and enhancing group IVC iPLA2 (cPLA 2γ) protein expression,” American Journal of Physiology—Lung Cellular and Molecular Physiology, vol. 287, no. 3, pp. L497–L502, 2004. View at Publisher · View at Google Scholar · View at Scopus
  104. G. M. Lord, G. Matarese, J. K. Howard, R. J. Baker, S. R. Bloom, and R. I. Lechler, “Leptin modulates the T-cell immune response and reverses starvation- induced immunosuppression,” Nature, vol. 394, no. 6696, pp. 897–901, 1998. View at Publisher · View at Google Scholar · View at Scopus
  105. J. Deng, Y. Liu, M. Yang et al., “Leptin exacerbates collagen-induced arthritis via enhancement of Th17 cell response,” Arthritis & Rheumatism, vol. 64, no. 11, pp. 3564–3573, 2012. View at Google Scholar
  106. M. Porter, M. Karp, S. Killedar et al., “Diesel-enriched particulate matter functionally activates human dendritic cells,” American Journal of Respiratory Cell and Molecular Biology, vol. 37, no. 6, pp. 706–719, 2007. View at Google Scholar
  107. H.-J. Woo, W. J. Yoo, C. H. Bae et al., “Leptin up-regulates MUC5B expression in human airway epithelial cells via mitogen-activated protein kinase pathway,” Experimental Lung Research, vol. 36, no. 5, pp. 262–269, 2010. View at Publisher · View at Google Scholar · View at Scopus
  108. J. Taildeman, C. A. Pérez-Novo, I. Rottiers et al., “Human mast cells express leptin and leptin receptors,” Histochemistry and Cell Biology, vol. 131, no. 6, pp. 703–711, 2009. View at Publisher · View at Google Scholar · View at Scopus
  109. S. A. Shore, I. N. Schwartzman, M. S. Mellema, L. Flynt, A. Imrich, and R. A. Johnston, “Effect of leptin on allergic airway responses in mice,” Journal of Allergy and Clinical Immunology, vol. 115, no. 1, pp. 103–109, 2005. View at Publisher · View at Google Scholar · View at Scopus
  110. A. S. Williams, S.-Y. Leung, P. Nath et al., “Role of TLR2, TLR4, and MyD88 in murine ozone-induced airway hyperresponsiveness and neutrophilia,” Journal of Applied Physiology, vol. 103, no. 4, pp. 1189–1195, 2007. View at Publisher · View at Google Scholar · View at Scopus
  111. R. A. Johnston, T. A. Theman, R. D. Terry, E. S. Williams, and S. A. Shore, “Pulmonary responses to acute ozone exposure in fasted mice: effect of leptin administration,” Journal of Applied Physiology, vol. 102, no. 1, pp. 149–156, 2007. View at Publisher · View at Google Scholar · View at Scopus
  112. N. Ali Assad and A. Sood, “Leptin, adiponectin and pulmonary diseases,” Biochimie, vol. 94, no. 10, pp. 2180–2189, 2012. View at Publisher · View at Google Scholar · View at Scopus
  113. E. Arteaga-Solis, T. Zee, C. W. Emala, C. Vinson, J. Wess, and G. Karsenty, “Inhibition of leptin regulation of parasympathetic signaling as a cause of extreme body weight-associated asthma,” Cell Metabolism, vol. 17, no. 1, pp. 35–48, 2013. View at Google Scholar
  114. R. A. Johnston, T. A. Theman, F. L. Lu, R. D. Terry, E. S. Williams, and S. A. Shore, “Diet-induced obesity causes innate airway hyperresponsiveness to methacholine and enhances ozone-induced pulmonary inflammation,” Journal of Applied Physiology, vol. 104, no. 6, pp. 1727–1735, 2008. View at Publisher · View at Google Scholar · View at Scopus
  115. R. A. Johnston, T. A. Theman, and S. A. Shore, “Augmented responses to ozone in obese carboxypeptidase E-deficient mice,” American Journal of Physiology—Regulatory Integrative and Comparative Physiology, vol. 290, no. 1, pp. R126–R133, 2006. View at Publisher · View at Google Scholar · View at Scopus
  116. A. Lessard, J. St-Laurent, H. Turcotte, and L.-P. Boulet, “Leptin and adiponectin in obese and non-obese subjects with asthma,” Biomarkers, vol. 16, no. 3, pp. 271–273, 2011. View at Publisher · View at Google Scholar · View at Scopus
  117. N. L. Lugogo, J. W. Hollingsworth, D. L. Howell et al., “Alveolar macrophages from overweight/obese subjects with asthma demonstrate a proinflammatory phenotype,” American Journal of Respiratory and Critical Care Medicine, vol. 186, no. 5, pp. 404–411, 2012. View at Google Scholar
  118. A. Sood, B. K. Dawson, W. Eid, L. E. Eagleton, J. Q. Henkle, and P. Hopkins-Price, “Obesity is associated with bronchial hyper-responsiveness in women,” Journal of Asthma, vol. 42, no. 10, pp. 847–852, 2005. View at Publisher · View at Google Scholar · View at Scopus
  119. C. M. Steppan, S. T. Bailey, S. Bhat et al., “The hormone resistin links obesity to diabetes,” Nature, vol. 409, no. 6818, pp. 307–312, 2001. View at Publisher · View at Google Scholar · View at Scopus
  120. C. Fang, Q. Meng, H. Wu et al., “Resistin-like molecule-β is a human airway remodelling mediator,” European Respiratory Journal, vol. 39, no. 2, pp. 458–466, 2012. View at Publisher · View at Google Scholar · View at Scopus
  121. M. S. Jamaluddin, S. M. Weakley, Q. Yao, and C. Chen, “Resistin: functional roles and therapeutic considerations for cardiovascular disease,” British Journal of Pharmacology, vol. 165, no. 3, pp. 622–632, 2012. View at Publisher · View at Google Scholar · View at Scopus
  122. H. Hirai, H. Satoh, A. Kudoh, and T. Watanabe, “Interaction between resistin and adiponectin in the proliferation of rat vascular smooth muscle cells,” Molecular and Cellular Endocrinology, vol. 366, no. 1, pp. 108–116, 2013. View at Google Scholar