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Cited by 411Adipokines, Inflammation, and Metabolic DiseasesRegulation of Appetite and ObesityCytokine Signaling Pathways and Interactions

Obesity, Fat Mass and Immune System: Role for Leptin

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Francisco, Vera, Pino, Jesús, Campos-Cabaleiro, Victor, Ruiz-Fernández, Clara, Mera, Antonio, Gonzalez-Gay, Miguel A., Gómez, Rodolfo, Gualillo, Oreste·2018·Frontiers in Physiology
DOI 10.3389/fphys.2018.00640PMC PMC5992476
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Abstract

Obesity is an epidemic disease characterized by chronic low-grade inflammation associated with a dysfunctional fat mass. Adipose tissue is now considered an extremely active endocrine organ that secretes cytokine-like hormones, called adipokines, either pro- or anti-inflammatory factors bridging metabolism to the immune system. Leptin is historically one of most relevant adipokines, with important physiological roles in the central control of energy metabolism and in the regulation of metabolism-immune system interplay, being a cornerstone of the emerging field of immunometabolism. Indeed, leptin receptor is expressed throughout the immune system and leptin has been shown to regulate both innate and adaptive immune responses. This review discusses the latest data regarding the role of leptin as a mediator of immune system and metabolism, with particular emphasis on its effects on obesity-associated metabolic disorders and autoimmune and/or inflammatory rheumatic diseases.

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  • Elevated leptin levels reduce the frequency of Tregs in individuals with obesity and mouse models.

    “In addition, elevated leptin levels have been shown to reduce the frequency of Tregs in both individuals with obesity and mouse models (Francisco et al. 2018).”

    From The double-edged sword of regulatory T cells in MASLD: from inflammation control to fibrosis promotion (2026) · cites this paper as Francisco et al. 2018

    The T Regulatory Cells subsection reports fewer Tregs in individuals with obesity, correlated with plasma leptin, and a higher Treg percentage in leptin-deficient mice that was reversed by leptin administration. The mouse evidence supports an effect of leptin, but the human finding is correlational; it does not show that elevated leptin caused the reduced Treg frequency in those individuals. No page number is provided in our copy. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

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  1. Acedo S. C. Gambero S. Cunha F. G. Lorand-Metze I. Gambero A. (2013). Participation of leptin in the determination of the macrophage phenotype: an additional role in adipocyte and macrophage crosstalk. In Vitro Cell. Dev. Biol. Anim. 49 473– 478. 10.1007/s11626-013-9629-x 23708919 · DOI
  2. Agrawal S. Gollapudi S. Su H. Gupta S. (2011). Leptin activates human B cells to secrete TNF-α, IL-6, and IL-10 via JAK2/STAT3 and p38MAPK/ERK1/2 signaling pathway. J. Clin. Immunol. 31 472– 478. 10.1007/s10875-010-9507-1 21243519 PMC3132280 · DOI
  3. Ajeganova S. Andersson M. L. Hafström I. (2013). Association of obesity with worse disease severity in rheumatoid arthritis as well as with comorbidities: a long-term followup from disease onset. Arthritis Care Res. 65 78– 87. 10.1002/acr.21710 22514159 · DOI
  4. Al-Hassi H. O. Bernardo D. Murugananthan A. U. Mann E. R. English N. R. Jones A. (2013). A mechanistic role for leptin in human dendritic cell migration: differences between ileum and colon in health and Crohn’s disease. Mucosal Immunol. 6 751– 761. 10.1038/mi.2012.113 23168838 PMC3684777 · DOI
  5. Al-Suhaimi E. A. Shehzad A. (2013). Leptin, resistin and visfatin: the missing link between endocrine metabolic disorders and immunity. Eur. J. Med. Res. 18: 12 10.1186/2047-783X-18-12 PMC3655867 23634778 · DOI
  6. Amarilyo G. Iikuni N. Liu A. Matarese G. La Cava A. (2014). Leptin enhances availability of apoptotic cell-derived self-antigen in systemic lupus erythematosus. PLoS One 9: e112826 10.1371/journal.pone.0112826 PMC4234630 25401752 · DOI
  7. Amarilyo G. Iikuni N. Shi F. D. Liu A. Matarese G. La Cava A. (2013). Leptin promotes lupus T-cell autoimmunity. Clin. Immunol. 149 530– 533. 10.1016/j.clim.2013.09.002 24263282 · DOI
  8. Anders H. J. Rihl M. Heufelder A. Loch O. Schattenkirchner M. (1999). Leptin serum levels are not correlated with disease activity in patients with rheumatoid arthritis. Metabolism 48 745– 748. 10.1016/S0026-0495(99)90174-9 10381149 · DOI
  9. Arrese M. Cabrera D. Kalergis A. M. Feldstein A. E. (2016). Innate immunity and inflammation in NAFLD/NASH. Dig. Dis. Sci. 61 1294– 1303. 10.1007/s10620-016-4049-x 26841783 PMC4948286 · DOI
  10. Bähr I. Goritz V. Doberstein H. Gesine G. Hiller R. Rosenstock P. (2017). Diet-induced obesity is associated with an impaired NK cell function and an increased colon cancer incidence. J. Nutr. Metab. 2017: 4297025 10.1155/2017/4297025 PMC5357539 28357137 · DOI
  11. Bao J. P. Chen W. P. Feng J. Hu P. F. Shi Z. L. Wu L. D. (2010). Leptin plays a catabolic role on articular cartilage. Mol. Biol. Rep. 37 3265– 3272. 10.1007/s11033-009-9911-x 19876764 · DOI
  12. Batra A. Okur B. Glauben R. Erben U. Ihbe J. Stroh T. (2010). Leptin: a critical regulator of CD4+ T-cell polarization in vitro and in vivo. Endocrinology 151 56– 62. 10.1210/en.2009-0565 19966187 · DOI
  13. Bennett B. D. Solar G. P. Yuan J. Q. Mathias J. Thomas G. R. Matthews W. (1996). A role for leptin and its cognate receptor in hematopoiesis. Curr. Biol. 6 1170– 1180. 10.1016/S0960-9822(02)70684-2 8805376 · DOI
  14. Benomar Y. Naour N. Aubourg A. Bailleux V. Gertler A. Djiane J. (2006). Insulin and leptin induce Glut4 plasma membrane translocation and glucose uptake in a human neuronal cell line by a phosphatidylinositol 3-kinase-dependent mechanism. Endocrinology 147 2550– 2556. 10.1210/en.2005-1464 16497805 · DOI
  15. Bhupathiraju S. Hu F. (2016). Epidemiology of obesity and diabetes and their cardiovascular complications. Circ. Res. 118 1723– 1735. 10.1161/CIRCRESAHA.115.306825 27230638 PMC4887150 · DOI
  16. Bjorbaek C. Uotani S. Da Silva B. Flier J. S. Bjørbæk C. Uotani S. (1997). Divergent signaling capacities of the long and short isoforms of the leptin receptor. J. Biol. Chem. 272 32686– 32695. 10.1074/jbc.272.51.32686 9405487 · DOI · Paper page
  17. Boi S. K. Buchta C. M. Pearson N. A. Francis M. B. Meyerholz D. K. Grobe J. L. (2016). Obesity alters immune and metabolic profiles: new insight from obese-resistant mice on high-fat diet. Obesity 24 2140– 2149. 10.1002/oby.21620 27515998 PMC5039085 · DOI
  18. Brotfain E. Hadad N. Shapira Y. Avinoah E. Zlotnik A. Raichel L. (2015). Neutrophil functions in morbidly obese subjects. Clin. Exp. Immunol. 181 156– 163. 10.1111/cei.12631 25809538 PMC4469166 · DOI
  19. Bruno A. Conus S. Schmid I. Simon H.-U. (2005). Apoptotic pathways are inhibited by leptin receptor activation in neutrophils. J. Immunol. 174 8090– 8096. 10.4049/jimmunol.174.12.8090 15944317 · DOI
  20. Busso N. So A. Chobaz-Peclat V. Morard C. Martinez-Soria E. Talabot-Ayer D. (2002). Leptin signaling deficiency impairs humoral and cellular immune responses and attenuates experimental arthritis. J. Immunol. 168 875– 882. 10.4049/jimmunol.168.2.875 11777985 · DOI
  21. Byrne C. D. Targher G. (2015). NAFLD: a multisystem disease. J. Hepatol. 62 S47– S64. 10.1016/j.jhep.2014.12.012 25920090 · DOI
  22. Caldefie-Chezet F. Poulin A. Tridon A. Sion B. Vasson M. P. (2001). Leptin: a potential regulator of polymorphonuclear neutrophil bactericidal action? J. Leukoc. Biol. 69 414– 418. 11261788
  23. Caldefie-Chezet F. Poulin A. Vasson M.-P. (2003). Leptin regulates functional capacities of polymorphonuclear neutrophils. Free Radic. Res. 37 809– 814. 10.1080/1071576031000097526 14567439 · DOI
  24. Cannon J. G. Sharma G. Sloan G. Dimitropoulou C. Baker R. R. Mazzoli A. (2014). Leptin regulates CD16 expression on human monocytes in a sex-specific manner. Physiol. Rep. 2: e12177 10.14814/phy2.12177 PMC4254102 25303952 · DOI
  25. Cao H. Lin J. Chen W. Xu G. Sun C. (2016). Baseline adiponectin and leptin levels in predicting an increased risk of disease activity in rheumatoid arthritis: a meta-analysis and systematic review. Autoimmunity 49 1– 7. 10.1080/08916934.2016.1230847 27690205 · DOI
  26. Carlton E. D. Demas G. E. French S. S. (2012). Leptin, a neuroendocrine mediator of immune responses, inflammation, and sickness behaviors. Horm. Behav. 62 272– 279. 10.1016/j.yhbeh.2012.04.010 22561456 · DOI
  27. Cassano S. Pucino V. La Rocca C. Procaccini C. De Rosa V. Marone G. (2014). Leptin modulates autophagy in human CD4+CD25- conventional T cells. Metabolism 63 1272– 1279. 10.1016/j.metabol.2014.06.010 25060689 PMC4180014 · DOI
  28. Chang S. F. Hsieh R. Z. Huang K. C. Chang C. A. Chiu F. Y. Kuo H. C. (2015). Upregulation of bone morphogenetic protein-2 synthesis and consequent collagen II expression in leptin-stimulated human chondrocytes. PLoS One 10: e0144252 10.1371/journal.pone.0144252 PMC4670096 26636769 · DOI
  29. Chatterjee S. Ganini D. Tokar E. J. Kumar A. Das S. Corbett J. (2013). Leptin is key to peroxynitrite-mediated oxidative stress and Kupffer cell activation in experimental non-alcoholic steatohepatitis. J. Hepatol. 58 778– 784. 10.1016/j.jhep.2012.11.035 23207144 PMC3596459 · DOI
  30. Chimenti M. S. Triggianese P. Conigliaro P. Candi E. Melino G. Perricone R. (2015). The interplay between inflammation and metabolism in rheumatoid arthritis. Cell Death Dis. 6: e1887 10.1038/cddis.2015.246 PMC4650442 26379192 · DOI
  31. Chitturi S. Farrell G. Frost L. Kriketos A. Lin R. Fung C. (2002). Serum leptin in NASH correlates with hepatic steatosis but not fibrosis: a manifestation of lipotoxicity? Hepatology 36 403– 409. 10.1053/jhep.2002.34738 12143049 · DOI
  32. Claycombe K. King L. E. Fraker P. J. (2008). A role for leptin in sustaining lymphopoiesis and myelopoiesis. Proc. Natl. Acad. Sci. U.S.A. 105 2017– 2021. 10.1073/pnas.0712053105 18250302 PMC2538874 · DOI
  33. Cohen S. Danzaki K. MacIver N. J. (2017). Nutritional effects on T-cell immunometabolism. Eur. J. Immunol. 47 225– 235. 10.1002/eji.201646423 28054344 PMC5342627 · DOI
  34. Conde J. Gomez R. Bianco G. Scotece M. Lear P. Dieguez C. (2011a). Expanding the adipokine network in cartilage: identification and regulation of novel factors in human and murine chondrocytes. Ann. Rheum. Dis. 70 551– 559. 10.1136/ard.2010.132399 21216818 · DOI
  35. Conde J. Scotece M. Abella V. Gómez R. López V. Villar R. (2015). Identification of novel adipokines in the joint. Differential expression in healthy and osteoarthritis tissues. PLoS One 10: e0123601 10.1371/journal.pone.0123601 PMC4390373 25853553 · DOI
  36. Conde J. Scotece M. Gomez R. Lopez V. Gomez-Reino J. J. Gualillo O. (2011b). Adipokines and osteoarthritis: novel molecules involved in the pathogenesis and progression of disease. Arthritis 2011: 203901 10.1155/2011/203901 PMC3200120 22046513 · DOI
  37. Conde J. Scotece M. López V. Abella V. Hermida M. Pino J. (2013). Differential expression of adipokines in infrapatellar fat pad (IPFP) and synovium of osteoarthritis patients and healthy individuals. Ann. Rheum. Dis. 73 631– 633. 10.1136/annrheumdis-2013-204189 24099837 · DOI
  38. Conde J. Scotece M. López V. Gómez R. Lago F. Pino J. (2012). Adiponectin and leptin induce VCAM-1 expression in human and murine chondrocytes. PLoS One 7: e52533 10.1371/journal.pone.0052533 PMC3526577 23285079 · DOI
  39. Curat C. A. Miranville A. Sengenès C. Diehl M. Tonus C. Busse R. (2004). From blood monocytes to adipose tissue-resident macrophages: induction of diapedesis by human mature adipocytes. Diabetes Metab. Res. Rev. 53 1285– 1292. 10.2337/diabetes.53.5.1285 15111498 · DOI · Paper page
  40. Dayakar A. Chandrasekaran S. Veronica J. Maurya R. (2016). Leptin induces the phagocytosis and protective immune response in Leishmania donovani infected THP-1 cell line and human PBMCs. Exp. Parasitol. 160 54– 59. 10.1016/j.exppara.2015.12.002 26688099 · DOI
  41. de Boer T. N. van Spil W. E. Huisman A. M. Polak A. A. Bijlsma J. W. Lafeber F. P. (2012). Serum adipokines in osteoarthritis; comparison with controls and relationship with local parameters of synovial inflammation and cartilage damage. Osteoarthritis Cartilage 20 846– 853. 10.1016/j.joca.2012.05.002 22595228 · DOI
  42. De Rosa V. La Cava A. Matarese G. (2017). Metabolic pressure and the breach of immunological self-tolerance. Nat. Immunol. 18 1190– 1196. 10.1038/ni.3851 29044230 · DOI
  43. De Rosa V. Procaccini C. Calì G. Pirozzi G. Fontana S. Zappacosta S. (2007). A key role of leptin in the control of regulatory T cell proliferation. Immunity 26 241– 255. 10.1016/j.immuni.2007.01.011 17307705 · DOI
  44. Deiuliis J. A. (2016). MicroRNAs as regulators of metabolic disease: pathophysiologic significance and emerging role as biomarkers and therapeutics. Int. J. Obes. 40 88– 101. 10.1038/ijo.2015.170 PMC4722234 26311337 · DOI
  45. Deng J. Liu Y. Yang M. Wang S. Zhang M. Wang X. (2012). Leptin exacerbates collagen-induced arthritis via enhancement of Th17 cell response. Arthritis Rheum. 64 3564– 3573. 10.1002/art.34637 22833425 · DOI
  46. DePaoli A. M. (2014). Leptin in common obesity and associated disorders of metabolism. J. Endocrinol. 223 T71– T81. 10.1530/JOE-14-0258 24973357 · DOI · Paper page
  47. Dib L. H. Ortega M. T. Melgarejo T. Chapes S. K. (2016). Establishment and characterization of DB-1: a leptin receptor-deficient murine macrophage cell line. Cytotechnology 68 921– 933. 10.1007/s10616-015-9843-3 25599862 PMC4960141 · DOI
  48. Dixit V. D. Mielenz M. Taub D. D. Parvizi N. (2003). Leptin induces growth hormone secretion from peripheral blood mononuclear cells via a protein kinase C- and nitric oxide-dependent mechanism. Endocrinology 144 5595– 5603. 10.1210/en.2003-0600 12970164 · DOI
  49. do Carmo L. S. Rogero M. M. Paredes-Gamero E. J. Nogueira-Pedro A. Xavier J. G. Cortez M. (2013). A high-fat diet increases interleukin-3 and granulocyte colony-stimulating factor production by bone marrow cells and triggers bone marrow hyperplasia and neutrophilia in Wistar rats. Exp. Biol. Med. 238 375– 384. 10.1177/1535370213477976 23760003 · DOI
  50. Donath M. Y. (2014). Targeting inflammation in the treatment of type 2 diabetes: time to start. Nat. Rev. Drug Discov. 13 465– 476. 10.1038/nrd4275 24854413 · DOI · Paper page
  51. Duarte G. V. Oliveira M. de F. Cardoso T. M. Follador I. Silva T. S. (2013). Association between obesity measured by different parameters and severity of psoriasis. Int. J. Dermatol. 52 177– 181. 10.1111/j.1365-4632.2011.05270.x 22998685 · DOI
  52. Ducy P. Amling M. Takeda S. Priemel M. Schilling A. F. Beil F. T. (2000). Leptin inhibits bone formation through a hypothalamic relay: a central control of bone mass. Cell 100 197– 207. 10.1016/S0092-8674(00)81558-5 10660043 · DOI · Paper page
  53. Dumond H. Presle N. Terlain B. Mainard D. Loeuille D. Netter P. (2003). Evidence for a key role of leptin in osteoarthritis. Arthritis Rheum. 48 3118– 3129. 10.1002/art.11303 14613274 · DOI
  54. Fan Q. Liu Z. Shen C. Li H. Ding J. Jin F. (2018). Microarray study of gene expression profile to identify new candidate genes involved in the molecular mechanism of leptin- induced knee joint osteoarthritis in rat. Hereditas 155: 4 10.1186/s41065-017-0039-z PMC5496599 28690479 · DOI
  55. Farooqi I. S. Matarese G. Lord G. M. Keogh J. M. Lawrence E. Agwu C. (2002). Beneficial effects of leptin on obesity, T cell hyporesponsiveness, and neuroendocrine/metabolic dysfunction of human congenital leptin deficiency. J. Clin. Invest. 110 1093– 1103. 10.1172/JCI15693 12393845 PMC150795 · DOI
  56. Favreau M. Menu E. Gaublomme D. Vanderkerken K. Faict S. Maes K. (2017). Leptin receptor antagonism of iNKT cell function: a novel strategy to combat multiple myeloma. Leukemia 31 2678– 2685. 10.1038/leu.2017.146 28490813 · DOI
  57. Figenschau Y. Knutsen G. Shahazeydi S. Johansen O. Sveinbjörnsson B. (2001). Human articular chondrocytes express functional leptin receptors. Biochem. Biophys. Res. Commun. 287 190– 197. 10.1006/bbrc.2001.5543 11549273 · DOI
  58. Findlay D. M. Atkins G. J. (2014). Osteoblast-chondrocyte interactions in osteoarthritis. Curr. Osteoporos. Rep. 12 127– 134. 10.1007/s11914-014-0192-5 24458429 PMC3933767 · DOI
  59. Frasca D. Ferracci F. Diaz A. Romero M. Lechner S. Blomberg B. B. (2016). Obesity decreases B cell responses in young and elderly individuals. Obesity 24 615– 625. 10.1002/oby.21383 26857091 PMC4769695 · DOI · Paper page
  60. Fraser D. A. Thoen J. Reseland J. E. Førre O. Kjeldsen-Kragh J. (1999). Decreased CD4+ lymphocyte activation and increased interleukin-4 production in peripheral blood of rheumatoid arthritis patients after acute starvation. Clin. Rheumatol. 18 394– 401. 10.1007/s100670050125 10524554 · DOI
  61. Frederich R. C. Hamann A. Anderson S. Löllmann B. Lowell B. B. Flier J. S. (1995). Leptin levels reflect body lipid content in mice: evidence for diet-induced resistance to leptin action. Nat. Med. 1 1311– 1314. 10.1038/nm1295-1311 7489415 · DOI · Paper page
  62. Frühbeck G. (2006). Intracellular signalling pathways activated by leptin. Biochem. J. 393 7– 20. 10.1042/BJ20051578 16336196 PMC1383660 · DOI
  63. Fujita Y. Fujii T. Mimori T. Sato T. Nakamura T. Iwao H. (2014). Deficient leptin signaling ameliorates systemic lupus erythematosus lesions in MRL/Mp-Fas lpr mice. J. Immunol. 192 979– 984. 10.4049/jimmunol.1301685 24391210 PMC3897175 · DOI
  64. Fujita Y. Yanagida H. Mimori T. Jin Z. X. Sakai T. Kawanami T. (2012). Prevention of fasting-mediated bone marrow atrophy by leptin administration. Cell. Immunol. 273 52– 58. 10.1016/j.cellimm.2011.11.007 22196379 · DOI
  65. Gabay C. Dreyer M. G. Pellegrinelli N. Chicheportiche R. Meier C. A. (2001). Leptin directly induces the secretion of interleukin 1 receptor antagonist in human monocytes. J. Clin. Endocrinol. Metab. 86 783– 791. 10.1210/jc.86.2.783 11158047 · DOI
  66. Gatto M. Zen M. Ghirardello A. Bettio S. Bassi N. Iaccarino L. (2013). Emerging and critical issues in the pathogenesis of lupus. Autoimmun. Rev. 12 523– 536. 10.1016/j.autrev.2012.09.003 23000207 · DOI
  67. Genovese M. C. Van den Bosch F. Roberson S. A. Bojin S. Biagini I. M. Ryan P. (2010). LY2439821, a humanized anti-interleukin-17 monoclonal antibody, in the treatment of patients with rheumatoid arthritis: a phase I randomized, double-blind, placebo-controlled, proof-of-concept study. Arthritis Rheum. 62 929– 939. 10.1002/art.27334 20131262 · DOI
  68. Gerriets V. A. Danzaki K. Kishton R. J. Eisner W. Nichols A. G. Saucillo D. C. (2016). Leptin directly promotes T-cell glycolytic metabolism to drive effector T-cell differentiation in a mouse model of autoimmunity. Eur. J. Immunol. 46 1970– 1983. 10.1002/eji.201545861 27222115 PMC5154618 · DOI
  69. Gerriets V. A. MacIver N. J. (2014). Role of T cells in malnutrition and obesity. Front. Immunol. 5: 379 10.3389/fimmu.2014.00379 PMC4127479 25157251 · DOI
  70. Gomez R. Scotece M. Conde J. Gomez-Reino J. J. Lago F. Gualillo O. (2011). Adiponectin and leptin increase IL-8 production in human chondrocytes. Ann. Rheum. Dis. 70 2052– 2054. 10.1136/ard.2010.145672 21622999 · DOI
  71. Griffin T. M. Huebner J. L. Kraus V. B. Guilak F. (2009). Extreme obesity due to impaired leptin signaling in mice does not cause knee osteoarthritis. Arthritis Rheum. 60 2935– 2944. 10.1002/art.24854 19790050 PMC2829313 · DOI
  72. Grotta M. B. Squebola-Cola D. M. Toro A. A. Ribeiro M. A. Mazon S. B. Ribeiro J. D. (2013). Obesity increases eosinophil activity in asthmatic children and adolescents. BMC Pulm. Med. 13: 39 10.1186/1471-2466-13-39 PMC3686646 23773659 · DOI
  73. Gruen M. L. Hao M. Piston D. W. Hasty A. H. (2007). Leptin requires canonical migratory signaling pathways for induction of monocyte and macrophage chemotaxis. AJP Cell Physiol. 293 C1481– C1488. 10.1152/ajpcell.00062.2007 17728393 · DOI
  74. Gupta S. Agrawal S. Gollapudi S. (2013). Increased activation and cytokine secretion in B cells stimulated with leptin in aged humans. Immun. Ageing 10: 3 10.1186/1742-4933-10-3 PMC3557206 23343052 · DOI
  75. Gutierrez D. A. Hasty A. H. (2012). Haematopoietic leptin receptor deficiency does not affect macrophage accumulation in adipose tissue or systemic insulin sensitivity. J. Endocrinol. 212 343– 351. 10.1530/JOE-11-0338 22194312 PMC3381898 · DOI
  76. Hizmetli S. Kisa M. Gokalp N. Bakici M. Z. (2007). Are plasma and synovial fluid leptin levels correlated with disease activity in rheumatoid arthritis? Rheumatol. Int. 27 335– 338. 10.1007/s00296-006-0264-7 17102942 · DOI
  77. Howard J. K. Lord G. M. Matarese G. Vendetti S. Ghatei M. A. Ritter M. A. (1999). Leptin protects mice from starvation-induced lymphoid atrophy and increases thymic cellularity in ob/ob mice. J. Clin. Invest. 104 1051– 1059. 10.1172/JCI6762 10525043 PMC408574 · DOI
  78. Huertas A. Phan C. Bordenave J. Tu L. Thuillet R. Le Hiress M. (2016). Regulatory T cell dysfunction in idiopathic, heritable and connective tissue-associated pulmonary arterial hypertension. Chest 149 1482– 1493. 10.1016/j.chest.2016.01.004 26836928 · DOI
  79. Huh J. Y. Park Y. J. Ham M. Kim J. B. (2014). Crosstalk between adipocytes and immune cells in adipose tissue inflammation and metabolic dysregulation in obesity. Mol. Cells 37 365– 371. 10.14348/molcells.2014.0074 24781408 PMC4044307 · DOI
  80. Hui W. Litherland G. J. Elias M. S. Kitson G. I. Cawston T. E. Rowan A. D. (2012). Leptin produced by joint white adipose tissue induces cartilage degradation via upregulation and activation of matrix metalloproteinases. Ann. Rheum. Dis. 71 455– 462. 10.1136/annrheumdis-2011-200372 22072016 · DOI
  81. Ikejima K. Okumura K. Lang T. Honda H. Abe W. Yamashina S. (2005). The role of leptin in progression of non-alcoholic fatty liver disease. Hepatol. Res. 33 151– 154. 10.1016/j.hepres.2005.09.024 16198623 · DOI
  82. Ikejima K. Takei Y. Honda H. Hirose M. Yoshikawa M. Zhang Y. J. (2002). Leptin receptor-mediated signaling regulates hepatic fibrogenesis and remodeling of extracellular matrix in the rat. Gastroenterology 122 1399– 1410. 10.1053/gast.2002.32995 11984526 · DOI
  83. Inzaugarat M. E. De Matteo E. Baz P. Lucero D. Garcia C. C. Ballerga E. G. (2017). New evidence for the therapeutic potential of curcumin to treat nonalcoholic fatty liver disease in humans. PLoS One 12: e0172900 10.1371/journal.pone.0172900 PMC5336246 28257515 · DOI
  84. Jaedicke K. M. Roythorne A. Padget K. Todryk S. Preshaw P. M. Taylor J. J. (2013). Leptin up-regulates TLR2 in human monocytes. J. Leukoc. Biol. 93 561– 571. 10.1189/jlb.1211606 23341537 · DOI
  85. Jahn J. Spielau M. Brandsch C. Stangl G. I. Delank K. S. Bähr I. (2015). Decreased NK cell functions in obesity can be reactivated by fat mass reduction. Obesity 23 2233– 2241. 10.1002/oby.21229 26390898 · DOI
  86. Jennbacken K. Ståhlman S. Grahnemo L. Wiklund O. Fogelstrand L. (2013). Glucose impairs B-1 cell function in diabetes. Clin. Exp. Immunol. 174 129– 138. 10.1111/cei.12148 23731267 PMC3784220 · DOI
  87. Jones K. D. Thitiri J. Ngari M. Berkley J. A. (2014). Childhood malnutrition: toward an understanding of infection, inflammation, and antimicrobials. Food Nutr. Bull. 35(Suppl. 2), S64– S70. 10.1001/jama.2009.1266 25069296 PMC4257992 · DOI
  88. Kakuma T. Lee Y. Higa M. Wang Z. W. Pan W. Shimomura I. (2000). Leptin, troglitazone, and the expression of sterol regulatory element binding proteins in liver and pancreatic islets. Proc. Natl. Acad. Sci. U.S.A. 97 8536– 8541. 10.1073/pnas.97.15.8536 10900012 PMC26983 · DOI
  89. Kalra S. P. (2009). Central leptin gene therapy ameliorates diabetes type 1 and 2 through two independent hypothalamic relays: a benefit beyond weight and appetite regulation. Peptides 30 1957– 1963. 10.1016/j.peptides.2009.07.021 19647774 PMC2755606 · DOI
  90. Kamada Y. Takehara T. Hayashi N. (2008). Adipocytokines and liver disease. J. Gastroenterol. 43 811– 822. 10.1007/s00535-008-2213-6 19012034 · DOI
  91. Kamp V. M. Langereis J. D. van Aalst C. W. van der Linden J. A. Ulfman L. H. Koenderman L. (2013). Physiological concentrations of leptin do not affect human neutrophils. PLoS One 8: e73170 10.1371/journal.pone.0073170 PMC3774682 24066032 · DOI
  92. Kato H. Ueki S. Kamada R. Kihara J. Yamauchi Y. Suzuki T. (2011). Leptin has a priming effect on eotaxin-induced human eosinophil chemotaxis. Int. Arch. Allergy Immunol. 155 335– 344. 10.1159/000321195 21346363 · DOI
  93. Kavak K. S. Teter B. E. Hagemeier J. Zakalik K. Weinstock-Guttman B. Edwards K. (2015). Higher weight in adolescence and young adulthood is associated with an earlier age at multiple sclerosis onset. Mult. Scler. 21 858– 865. 10.1177/1352458514555787 25392327 · DOI
  94. Kiguchi N. Maeda T. Kobayashi Y. Fukazawa Y. Kishioka S. (2009). Leptin enhances CC-chemokine ligand expression in cultured murine macrophage. Biochem. Biophys. Res. Commun. 384 311– 315. 10.1016/j.bbrc.2009.04.121 19409880 · DOI
  95. Kim S. Y. Lim J. H. Choi S. W. Kim M. Kim S. T. Kim M. S. (2010). Preferential effects of leptin on CD4 T cells in central and peripheral immune system are critically linked to the expression of leptin receptor. Biochem. Biophys. Res. Commun. 394 562– 568. 10.1016/j.bbrc.2010.03.019 20227394 · DOI
  96. Klöting N. Blüher M. (2014). Adipocyte dysfunction, inflammation and metabolic syndrome. Rev. Endocr. Metab. Disord. 15 277– 287. 10.1007/s11154-014-9301-0 25344447 · DOI
  97. Koskinen A. Vuolteenaho K. Nieminen R. Moilanen T. Moilanen E. (2011). Leptin enhances MMP-1, MMP-3 and MMP-13 production in human osteoarthritic cartilage and correlates with MMP-1 and MMP-3 in synovial fluid from OA patients. Clin. Exp. Rheumatol. 29 57– 64. 21345293
  98. Koskinen-kolasa A. Vuolteenaho K. Korhonen R. Moilanen T. Moilanen E. (2016). Catabolic and proinflammatory effects of leptin in chondrocytes are regulated by suppressor of cytokine signaling-3. Arthritis Res. Ther. 215 1– 13. 10.1186/s13075-016-1112-0 PMC5048607 27716333 · DOI
  99. Kulkarni R. N. Wang Z. L. Wang R. M. Hurley J. D. Smith D. M. Ghatei M. A. (1997). Leptin rapidly suppresses insulin release from insulinoma cells, rat and human islets and, in vivo, in mice. J. Clin. Invest. 100 2729– 2736. 10.1172/JCI119818 9389736 PMC508476 · DOI · Paper page
  100. Lam Q. L. Liu S. Cao X. Lu L. (2006). Involvement of leptin signaling in the survival and maturation of bone marrow-derived dendritic cells. Eur. J. Immunol. 36 3118– 3130. 10.1002/eji.200636602 17125143 · DOI
  101. Lam Q. L. Wang S. Ko O. K. Kincade P. W. Lu L. (2010). Leptin signaling maintains B-cell homeostasis via induction of Bcl-2 and Cyclin D1. Proc. Natl. Acad. Sci. U.S.A. 107 13812– 13817. 10.1073/pnas.1004185107 20643953 PMC2922219 · DOI
  102. Lamas A. Lopez E. Carrio R. Lopez D. M. (2016). Adipocyte and leptin accumulation in tumor-induced thymic involution. Int. J. Mol. Med. 37 133– 138. 10.3892/ijmm.2015.2392 26530443 · DOI
  103. Lamas B. Goncalves-Mendes N. Nachat-Kappes R. Rossary A. Caldefie-Chezet F. Vasson M. P. (2013). Leptin modulates dose-dependently the metabolic and cytolytic activities of NK-92 cells. J. Cell. Physiol. 228 1202– 1209. 10.1002/jcp.24273 23129404 · DOI
  104. Laue T. Wrann C. D. Hoffmann-Castendiek B. Pietsch D. Hübner L. Kielstein H. (2015). Altered NK cell function in obese healthy humans. BMC Obes. 2: 1 10.1186/s40608-014-0033-1 PMC4511543 26217516 · DOI
  105. Lebovitz H. E. (2003). The relationship of obesity to the metabolic syndrome. Int. J. Clin. Pract. Suppl. 134 18– 27. 12793594
  106. Lee Y. H. Bae S. C. (2016). Circulating leptin level in rheumatoid arthritis and its correlation with disease activity: a meta-analysis. Z. Rheumatol. 75 1021– 1027. 10.1007/s00393-016-0050-1 26820722 · DOI
  107. Lee Y. H. Song G. G. (2018). Association between circulating leptin levels and systemic lupus erythematosus: an updated meta-analysis. Lupus 27 428– 435. 10.1177/0961203317725587 28795654 · DOI
  108. Li H. M. Zhang T. P. Leng R. X. Li X. P. Li X. M. Liu H. R. (2016). Emerging role of adipokines in systemic lupus erythematosus. Immunol. Res. 64 820– 830. 10.1007/s12026-016-8808-8 27314594 · DOI
  109. Li K. Wei L. Huang Y. Wu Y. Su M. Pang X. (2016). Leptin promotes breast cancer cell migration and invasion via IL-18 expression and secretion. Int. J. Oncol. 48 2479– 2487. 10.3892/ijo.2016.3483 27082857 · DOI
  110. Licinio J. Caglayan S. Ozata M. Yildiz B. O. de Miranda P. B. O’Kirwan F. (2004). Phenotypic effects of leptin replacement on morbid obesity, diabetes mellitus, hypogonadism, and behavior in leptin-deficient adults. Proc. Natl. Acad. Sci. U.S.A. 101 4531– 4536. 10.1073/pnas.0308767101 15070752 PMC384781 · DOI · Paper page
  111. Liu A. La Cava A. (2014). Epigenetic dysregulation in systemic lupus erythematosus. Autoimmunity 47 215– 219. 10.3109/08916934.2013.844794 24128164 · DOI
  112. Liu Y. Yu Y. Matarese G. La Cava A. (2012). Cutting edge: fasting-induced hypoleptinemia expands functional regulatory T cells in systemic lupus erythematosus. J. Immunol. 188 2070– 2073. 10.4049/jimmunol.1102835 22291185 PMC3288569 · DOI
  113. Lo C. Lam Q. L. Yang M. Ko K.-H. Sun L. Ma R. (2009). Leptin signaling protects NK cells from apoptosis during development in mouse bone marrow. Cell. Mol. Immunol. 6 353– 360. 10.1038/cmi.2009.46 19887048 PMC4003218 · DOI
  114. Loeser R. F. Goldring S. R. Scanzello C. R. Goldring M. B. (2012). Osteoarthritis: a disease of the joint as an organ. Arthritis Rheum. 64 1697– 1707. 10.1002/art.34453 22392533 PMC3366018 · DOI
  115. Lord G. M. Matarese G. Howard J. K. Baker R. J. Bloom S. R. Lechler R. I. (1998). Leptin modulates the T-cell immune response and reverses starvation-induced immunosuppression. Nature 394 897– 901. 10.1038/29795 9732873 · DOI
  116. Lord G. M. Matarese G. Howard J. K. Bloom S. R. Lechler R. I. (2002). Leptin inhibits the anti-CD3-driven proliferation of peripheral blood T cells but enhances the production of proinflammatory cytokines. J. Leukoc. Biol. 72 330– 338. 12149424
  117. Lourenço E. V. Liu A. Matarese G. La Cava A. (2016). Leptin promotes systemic lupus erythematosus by increasing autoantibody production and inhibiting immune regulation. Proc. Natl. Acad. Sci. U.S.A. 113 10637– 10642. 10.1073/pnas.1607101113 27588900 PMC5035847 · DOI
  118. Luan B. Goodarzi M. O. Phillips N. G. Guo X. Chen Y. D. Yao J. (2014). Leptin-mediated increases in catecholamine signaling reduce adipose tissue inflammation via activation of macrophage HDAC4. Cell Metab. 19 1058– 1065. 10.1016/j.cmet.2014.03.024 24768298 PMC4207085 · DOI
  119. Ma L. Li D. Sookha M. R. Fang M. Guan Y. Sun X. (2015). Elevated serum leptin levels in patients with systemic lupus erythematosus. Pharmazie 70 720– 723. 10.1691/ph.2015.5649 26790188 · DOI
  120. MacIver N. J. Michalek R. D. Rathmell J. C. (2013). Metabolic regulation of T lymphocytes. Annu. Rev. Immunol. 31 259– 283. 10.1146/annurev-immunol-032712-095956 23298210 PMC3606674 · DOI · Paper page
  121. Maingrette F. Renier G. (2003). Leptin increases lipoprotein lipase secretion by macrophages: involvement of oxidative stress and protein kinase C. Diabetes Metab. Res. Rev. 52 2121– 2128. 10.2337/diabetes.52.8.2121 12882931 · DOI
  122. Mancuso P. (2004). Leptin augments alveolar macrophage leukotriene synthesis by increasing phospholipase activity and enhancing group IVC iPLA2 (cPLA2gamma) protein expression. AJP Lung Cell. Mol. Physiol. 287 L497– L502. 10.1152/ajplung.00010.2004 15145787 · DOI
  123. Mancuso P. Myers M. G. Goel D. Serezani C. H. O’Brien E. Goldberg J. (2012). Ablation of leptin receptor-mediated ERK activation impairs host defense against Gram-negative pneumonia. J. Immunol. 189 867– 875. 10.4049/jimmunol.1200465 22685316 PMC3392451 · DOI
  124. Margiotta D. Navarini L. Vadacca M. Basta F. Vullo M. Pignataro F. (2016). Relationship between leptin and regulatory T cells in systemic lupus erythematosus?: preliminary results. Eur. Rev. Med. Pharmacol. Sci. 20 636– 641. 26957264
  125. Marques-Rocha J. L. Samblas M. Milagro F. I. Bressan J. Martínez J. A. Marti A. (2015). Noncoding RNAs, cytokines, and inflammation-related diseases. FASEB J. 29 3595– 3611. 10.1096/fj.14-260323 26065857 · DOI
  126. Martínez-Carrillo B. E. Jarillo-Luna R. A. Campos-Rodríguez R. Valdés-Ramos R. Rivera-Aguilar V. (2015). Effect of diet and exercise on the peripheral immune system in young Balb/c mice. Biomed Res. Int. 2015: 458470 10.1155/2015/458470 PMC4655039 26634209 · DOI
  127. Martín-Romero C. Santos-Alvarez J. Goberna R. Sánchez-Margalet V. (2000). Human leptin enhances activation and proliferation of human circulating monocytes. Cell. Immunol. 199 15– 24. 10.1006/cimm.1999.1490 10675271 · DOI
  128. Matarese G. (2000). Leptin and the immune system: how nutritional status influences the immune response. Eur. Cytokine Netw. 11 7– 13. 10.1519/JSC.0b013e3181bab493 10705294 · DOI
  129. Matarese G. Procaccini C. De Rosa V. Horvath T. L. La Cava A. (2010). Regulatory T cells in obesity: the leptin connection. Trends Mol. Med. 16 247– 256. 10.1016/j.molmed.2010.04.002 20493774 · DOI
  130. Mathis D. Shoelson S. E. (2011). Immunometabolism: an emerging frontier. Nat. Rev. Immunol. 11 81– 83. 10.1038/nri2922 21469396 PMC4784680 · DOI
  131. Mattioli B. Giordani L. Quaranta M. G. Viora M. (2009). Leptin exerts an anti-apoptotic effect on human dendritic cells via the PI3K-Akt signaling pathway. FEBS Lett. 583 1102– 1106. 10.1016/j.febslet.2009.02.029 19250936 · DOI
  132. Mattioli B. Straface E. Matarrese P. Quaranta M. G. Giordani L. Malorni W. (2008). Leptin as an immunological adjuvant: enhanced migratory and CD8+ T cell stimulatory capacity of human dendritic cells exposed to leptin. FASEB J. 22 2012– 2022. 10.1096/fj.07-098095 18218920 · DOI
  133. Maurya R. Bhattacharya P. Ismail N. Dagur P. K. Joshi A. B. Razdan K. (2016). Differential role of leptin as an immunomodulator in controlling visceral Leishmaniasis in normal and leptin-deficient mice. Am. J. Trop. Med. Hyg. 95 109– 119. 10.4269/ajtmh.15-0804 27114296 PMC4944674 · DOI
  134. Meier C. A. Chicheportiche R. Dreyer M. Dayer J. M. (2003). IP-10, but not RANTES, is upregulated by leptin in monocytic cells. Cytokine 21 43– 47. 10.1016/S1043-4666(02)00491-X 12668159 · DOI
  135. Mittendorfer B. Horowitz J. F. DePaoli A. M. McCamish M. A. Patterson B. W. Klein S. (2011). Recombinant human leptin treatment does not improve insulin action in obese subjects with type 2 diabetes. Diabetes Metab. Res. Rev. 60 1474– 1477. 10.2337/db10-1302 PMC3292320 21411512 · DOI
  136. Montecucco F. Bianchi G. Gnerre P. Bertolotto M. Dallegri F. Ottonello L. (2006). Induction of neutrophil chemotaxis by leptin: crucial role for p38 and Src kinases. Ann. N. Y. Acad. Sci. 1069 463– 471. 10.1196/annals.1351.045 16855174 · DOI
  137. Moraes-Vieira P. M. Larocca R. A. Bassi E. J. Peron J. P. Andrade-Oliveira V. Wasinski F. (2014). Leptin deficiency impairs maturation of dendritic cells and enhances induction of regulatory T and Th17 cells. Eur. J. Immunol. 44 794– 806. 10.1002/eji.201343592 24271843 PMC4973395 · DOI
  138. Morteza A. Nakhjavani M. Asgarani F. Ghaneei A. Esteghamati A. Mirmiranpour H. (2013). The lost correlation between leptin and CRP in type 2 diabetes. Eur. Cytokine Netw. 24 53– 59. 10.1684/ecn.2013.0329 23674518 · DOI
  139. Morton G. J. Gelling R. W. Niswender K. D. Morrison C. D. Rhodes C. J. Schwartz M. W. (2005). Leptin regulates insulin sensitivity via phosphatidylinositol-3-OH kinase signaling in mediobasal hypothalamic neurons. Cell Metab. 2 411– 420. 10.1016/j.cmet.2005.10.009 16330326 · DOI · Paper page
  140. Münzberg H. Morrison C. D. (2015). Structure, production and signaling of leptin. Metabolism 64 13– 23. 10.1016/j.metabol.2014.09.010 25305050 PMC4267896 · DOI
  141. Mutabaruka M.-S. Aoulad Aissa M. Delalandre A. Lavigne M. Lajeunesse D. (2010). Local leptin production in osteoarthritis subchondral osteoblasts may be responsible for their abnormal phenotypic expression. Arthritis Res. Ther. 12: R20 10.1186/ar2925 PMC2875652 20141628 · DOI
  142. Najib S. Sánchez-Margalet V. (2002). Human leptin promotes survival of human circulating blood monocytes prone to apoptosis by activation of p42/44 MAPK pathway. Cell. Immunol. 220 143– 149. 10.1016/S0008-8749(03)00027-3 12657249 · DOI
  143. Namkoong C. Kim M. S. Jang P. G. Han S. M. Park H. S. Koh E. H. (2005). Enhanced hypothalamic AMP-activated protein kinase activity contributes to hyperphagia in diabetic rats. Diabetes Metab. Res. Rev. 54 63– 68. 10.2337/diabetes.54.1.63 15616011 · DOI
  144. Nave H. Mueller G. Siegmund B. Jacobs R. Stroh T. Schueler U. (2008). Resistance of Janus kinase-2 dependent leptin signaling in natural killer (NK) Cells: a novel mechanism of NK cell dysfunction in diet-induced obesity. Endocrinology 149 3370– 3378. 10.1210/en.2007-1516 18356278 · DOI
  145. Naylor C. Burgess S. Madan R. Buonomo E. Razzaq K. Ralston K. (2014). Leptin receptor mutation results in defective neutrophil recruitment to the colon during Entamoeba histolytica infection. mBio 5: e02046– 14 10.1128/mBio.02046-14 PMC4271549 25516614 · DOI
  146. Nikolajczyk B. S. (2010). B cells as under-appreciated mediators of non-auto-immune inflammatory disease. Cytokine 50 234– 242. 10.1016/j.cyto.2010.02.022 20382544 PMC2917985 · DOI
  147. Nugent M. (2016). MicroRNAs: exploring new horizons in osteoarthritis. Osteoarthritis Cartilage 24 573– 580. 10.1016/j.joca.2015.10.018 26576510 · DOI
  148. Olama S. M. Senna M. K. Elarman M. (2012). Synovial/Serum leptin ratio in rheumatoid arthritis: the association with activity and erosion. Rheumatol. Int. 32 683– 690. 10.1007/s00296-010-1698-5 21140264 · DOI
  149. Oner S. Volkan O. Oner C. Mengi A. Direskeneli H. Da T. (2015). Serum leptin levels do not correlate with disease activity in rheumatoid arthritis. Acta Reumatol. Port. 40 50– 54. 25342093
  150. Orlova E. G. Shirshev S. V. (2014). Role of leptin and ghrelin in induction of differentiation of IL-17-producing and T-regulatory cells. Bull. Exp. Biol. Med. 156 819– 822. 10.1007/s10517-014-2459-3 24824706 · DOI
  151. O’Rourke L. Yeaman S. J. Shepherd P. R. (2001). Insulin and leptin acutely regulate cholesterol ester metabolism in macrophages by novel signaling pathways. Diabetes Metab. Res. Rev. 50 955– 961. 10.2337/diabetes.50.5.955 11334438 · DOI
  152. Otero M. Gomez Reino J. J. Gualillo O. (2003). Synergistic induction of nitric oxide synthase type II: in vitro effect of leptin and interferon-gamma in human chondrocytes and ATDC5 chondrogenic cells. Arthritis Rheum. 48 404– 409. 10.1002/art.10811 12571850 · DOI
  153. Otero M. Lago R. Gomez R. Lago F. Dieguez C. Gómez-Reino J. J. (2006). Changes in plasma levels of fat-derived hormones adiponectin, leptin, resistin and visfatin in patients with rheumatoid arthritis. Ann. Rheum. Dis. 65 1198– 1201. 10.1136/ard.2005.046540 16414972 PMC1798289 · DOI
  154. Otero M. Lago R. Gómez R. Lago F. Gomez-Reino J. J. Gualillo O. (2007). Phosphatidylinositol 3-kinase, MEK-1 and p38 mediate leptin/interferon-gamma synergistic NOS type II induction in chondrocytes. Life Sci. 81 1452– 1460. 10.1016/j.lfs.2007.09.007 17935739 · DOI
  155. Otero M. Lago R. Lago F. Reino J. J. Gualillo O. (2005). Signalling pathway involved in nitric oxide synthase type II activation in chondrocytes: synergistic effect of leptin with interleukin-1. Arthritis Res. Ther. 7 R581– R591. 10.1186/ar1708 15899045 PMC1174950 · DOI
  156. Otvos L. Shao W.-H. Vanniasinghe A. S. Amon M. A. Csilla Holub M. Kovalszky I. (2011). Toward understanding the role of leptin and leptin receptor antagonism in preclinical models of rheumatoid arthritis. Peptides 32 1567– 1574. 10.1016/j.peptides.2011.06.015 21723351 · DOI
  157. Ozata M. Uçkaya G. Beyhan Z. Ozdemir I. C. (1999). Plasma leptin levels in male patients with idiopathic central diabetes insipidus. J. Endocrinol. Invest. 22 451– 454. 10.1007/BF03343589 10435855 · DOI
  158. Pearson M. J. Herndler-Brandstetter D. Tariq M. A. Nicholson T. A. Philp A. M. Smith H. L. (2017). IL-6 secretion in osteoarthritis patients is mediated by chondrocyte-synovial fibroblast cross-talk and is enhanced by obesity. Sci. Rep. 7: 3451 10.1038/s41598-017-03759-w PMC5471184 28615667 · DOI
  159. Pelleymounter M. A. Cullen M. J. Baker M. B. Hecht R. Winters D. Boone T. (1995). Effects of the obese gene product on body weight regulation in ob/ob mice. Science 269 540– 543. 10.1126/science.7624776 7624776 · DOI · Paper page
  160. Pérez-Pérez A. Vilariño-García T. Fernández-Riejos P. Martín-González J. Segura-Egea J. J. Sánchez-Margalet V. (2017). Role of leptin as a link between metabolism and the immune system. Cytokine Growth Factor Rev. 35 71– 84. 10.1016/j.cytogfr.2017.03.001 28285098 · DOI
  161. Popa C. Netea M. G. Radstake T. R. D. van Riel P. L. Barrera P. van der Meer J. W. (2005). Markers of inflammation are negatively correlated with serum leptin in rheumatoid arthritis. Ann. Rheum. Dis. 64 1195– 1198. 10.1136/ard.2004.032243 15731289 PMC1755600 · DOI
  162. Procaccini C. De Rosa V. Galgani M. Carbone F. Cassano S. Greco D. (2012). Leptin-induced mTOR activation defines a specific molecular and transcriptional signature controlling CD4+ effector T cell responses. J. Immunol. 189 2941– 2953. 10.4049/jimmunol.1200935 22904304 · DOI
  163. Procaccini C. La Rocca C. Carbone F. De Rosa V. Galgani M. Matarese G. (2017). Leptin as immune mediator: interaction between neuroendocrine and immune system. Dev. Comp. Immunol. 66 120– 129. 10.1016/j.dci.2016.06.006 27288847 · DOI
  164. Rahmati M. Mobasheri A. Mozafari M. (2016). Inflammatory mediators in osteoarthritis: a critical review of the state-of-the-art, current prospects, and future challenges. Bone 85 81– 90. 10.1016/j.bone.2016.01.019 26812612 · DOI
  165. Ramirez O. Garza K. M. (2014). Leptin deficiency in vivo enhances the ability of splenic dendritic cells to activate T cells. Int. Immunol. 26 627– 636. 10.1093/intimm/dxu067 24966213 PMC4201843 · DOI
  166. Reis B. S. Lee K. Fanok M. H. Mascaraque C. Amoury M. Cohn L. B. (2015). Leptin receptor signaling in T cells is required for Th17 differentiation. J. Immunol. 194 5253– 5260. 10.4049/jimmunol.1402996 25917102 PMC4433844 · DOI
  167. Rodríguez L. Graniel J. Ortiz R. (2007). Effect of leptin on activation and cytokine synthesis in peripheral blood lymphocytes of malnourished infected children. Clin. Exp. Immunol. 148 478– 485. 10.1111/j.1365-2249.2007.03361.x 17355247 PMC1941936 · DOI
  168. Rosenbaum M. Leibel R. L. (2014). Role of leptin in energy homeostasis in humans. J. Endocrinol. 223 T83– T96. 10.1530/JOE-14-0358 25063755 PMC4454393 · DOI
  169. Sanchez-Margalet V. Martin-Romero C. (2001). Human leptin signaling in human peripheral blood mononuclear cells: activation of the JAK-STAT pathway. Cell. Immunol. 211 30– 36. 10.1006/cimm.2001.1815 11585385 · DOI
  170. Sánchez-Pozo C. Rodriguez-Baño J. Domínguez-Castellano A. Muniain M. A. Goberna R. Sánchez-Margalet V. (2003). Leptin stimulates the oxidative burst in control monocytes but attenuates the oxidative burst in monocytes from HIV-infected patients. Clin. Exp. Immunol. 134 464– 469. 10.1111/j.1365-2249.2003.02321.x 14632752 PMC1808878 · DOI
  171. Santos-Alvarez J. Goberna R. Sánchez-Margalet V. (1999). Human leptin stimulates proliferation and activation of human circulating monocytes. Cell. Immunol. 194 6– 11. 10.1006/cimm.1999.1490 10357875 · DOI
  172. Saucillo D. C. Gerriets V. A. Sheng J. Rathmell J. C. Maciver N. J. Stedman S. W. (2014). Leptin metabolically licenses T cells for activation to link nutrition and immunity. J. Immunol. 192 136– 144. 10.4049/jimmunol.1301158 24273001 PMC3872216 · DOI
  173. Saxena N. K. Ikeda K. Rockey D. C. Friedman S. L. (2002). Leptin in hepatic fibrosis: evidence for increased collagen production in stellate cells and lean littermates of ob/ob mice. Hepatology 35 762– 771. 10.1053/jhep.2002.32029 11915021 PMC2935193 · DOI · Paper page
  174. Schultze S. M. Hemmings B. A. Niessen M. Tschopp O. (2012). PI3K/AKT, MAPK and AMPK signalling: protein kinases in glucose homeostasis. Expert Rev. Mol. Med. 14: e1 10.1017/S1462399411002109 22233681 · DOI
  175. Scotece M. Conde J. López V. Lago F. Pino J. Gómez-Reino J. J. (2014). Adiponectin and leptin: new targets in inflammation. Basic Clin. Pharmacol. Toxicol. 114 97– 102. 10.1111/bcpt.12109 23834523 · DOI
  176. Scotece M. Pérez T. Conde J. Abella V. López V. Pino J. (2017). Adipokines induce pro-inflammatory factors in activated Cd4+ T cells from osteoarthritis patient. J. Orthop. Res. 35 1299– 1303. 10.1002/jor.23377 27472907 · DOI
  177. Seol D. McCabe D. J. Choe H. Zheng H. Yu Y. Jang K. (2012). Chondrogenic progenitor cells respond to cartilage injury. Arthritis Rheum. 64 3626– 3637. 10.1002/art.34613 22777600 PMC4950521 · DOI
  178. Silha J. V. Krsek M. Skrha J. V. Sucharda P. Nyomba B. L. Murphy L. J. (2003). Plasma resistin, adiponectin and leptin levels in lean and obese subjects: correlations with insulin resistence. Eur. J. Endocrinol. 149 331– 335. 10.1530/eje.0.1490331 14514348 · DOI
  179. Smolen J. S. Aletaha D. McInnes I. B. (2016). Rheumatoid arthritis. Lancet 388 2023– 2038. 10.1016/S0140-6736(16)30173-8 27156434 · DOI
  180. Sun Z. Dragon S. Becker A. Gounni A. S. (2013). Leptin inhibits neutrophil apoptosis in children via ERK/NF-κB-dependent pathways. PLoS One 8: e55249 10.1371/journal.pone.0055249 PMC3561393 23383125 · DOI
  181. Suzukawa M. Nagase H. Ogahara I. Han K. Tashimo H. Shibui A. (2011). Leptin enhances survival and induces migration, degranulation, and cytokine synthesis of human basophils. J. Immunol. 186 5254– 5260. 10.4049/jimmunol.1004054 21421855 · DOI
  182. Tacke F. Yoneyama H. (2013). From NAFLD to NASH to fibrosis to HCC: role of dendritic cell populations in the liver. Hepatology 58 494– 496. 10.1002/hep.26405 23519833 · DOI
  183. Tajiri K. Shimizu Y. (2012). Role of NKT cells in the pathogenesis of NAFLD. Int. J. Hepatol. 2012: 850836 10.1155/2012/850836 PMC3335183 22577564 · DOI
  184. Tanaka M. Suganami T. Kim-Saijo M. Toda C. Tsuiji M. Ochi K. (2011). Role of central leptin signaling in the starvation-induced alteration of B-cell development. J. Neurosci. 31 8373– 8380. 10.1523/JNEUROSCI.6562-10.2011 21653842 PMC6623333 · DOI
  185. Targońska-Stępniak B. Majdan M. Dryglewska M. (2008). Leptin serum levels in rheumatoid arthritis patients: relation to disease duration and activity. Rheumatol. Int. 28 585– 591. 10.1007/s00296-007-0480-9 17968549 · DOI
  186. Taylor A. K. Cao W. Vora K. P. De La Cruz J. Shieh W. J. Zaki S. R. (2013). Protein energy malnutrition decreases immunity and increases susceptibility to influenza infection in mice. J. Infect. Dis. 207 501– 510. 10.1093/infdis/jis527 22949306 PMC11341849 · DOI
  187. Tchang B. G. Shukla A. P. Aronne L. J. (2015). Metreleptin and generalized lipodystrophy and evolving therapeutic perspectives. Expert Opin. Biol. Ther. 15 1061– 1075. 10.1517/14712598.2015.1052789 26063386 · DOI · Paper page
  188. Tian G. Liang J.-N. Wang Z.-Y. Zhou D. (2014). Emerging role of leptin in rheumatoid arthritis. Clin. Exp. Immunol. 177 557– 570. 10.1111/cei.12372 24802245 PMC4137840 · DOI
  189. Tian Z. Chen Y. Gao B. (2013). Natural killer cells in liver disease. Hepatology 57 1654– 1662. 10.1002/hep.26115 23111952 PMC3573257 · DOI
  190. Tian Z. Sun R. Wei H. Gao B. (2002). 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. 10.1016/S0006-291X(02)02462-2 12413939 · DOI
  191. Tilg H. Moschen A. R. (2006). Adipocytokines: mediators linking adipose tissue, inflammation and immunity. Nat. Rev. Immunol. 6 772– 783. 10.1038/nri1937 16998510 · DOI
  192. Tiniakos D. G. Vos M. B. Brunt E. M. (2010). Nonalcoholic fatty liver disease: pathology and pathogenesis. Annu. Rev. Pathol. Mech. Dis. 5 145– 171. 10.1146/annurev-pathol-121808-102132 20078219 · DOI · Paper page
  193. Toussirot É. Michel F. Binda D. Dumoulin G. (2015). The role of leptin in the pathophysiology of rheumatoid arthritis. Life Sci. 140 29– 36. 10.1016/j.lfs.2015.05.001 26025594 · DOI
  194. Tsiotra P. C. Boutati E. Dimitriadis G. Raptis S. A. (2013). High insulin and leptin increase resistin and inflammatory cytokine production from human mononuclear cells. Biomed Res. Int. 2013: 487081 10.1155/2013/487081 PMC3591160 23484124 · DOI
  195. Tsiotra P. C. Pappa V. Raptis S. A. Tsigos C. (2000). Expression of the long and short leptin receptor isoforms in peripheral blood mononuclear cells: implications for leptin’s actions. Metabolism 49 1537– 1541. 10.1053/meta.2000.18519 11145113 · DOI
  196. Tsochatzis E. A. Papatheodoridis G. V. Archimandritis A. J. (2009). Adipokines in nonalcoholic steatohepatitis: from pathogenesis to implications in diagnosis and therapy. Mediators Inflamm. 2009: 831670 10.1155/2009/831670 PMC2694309 19753129 · DOI
  197. Ubags N. D. Vernooy J. H. Burg E. Hayes C. Bement J. Dilli E. (2014). The role of leptin in the development of pulmonary neutrophilia in infection and Acute Lung Injury. Crit. Care Med. 42 143– 151. 10.1097/CCM.0000000000000048 PMC3947045 24231757 · DOI
  198. Vestweber D. (2015). How leukocytes cross the vascular endothelium. Nat. Rev. Immunol. 15 692– 704. 10.1038/nri3908 26471775 · DOI · Paper page
  199. Vieira-Potter V. J. (2014). Inflammation and macrophage modulation in adipose tissues. Cell. Microbiol. 16 1484– 1492. 10.1111/cmi.12336 25073615 · DOI
  200. Voloshyna I. Mounessa J. Carsons S. E. Reiss A. B. (2016). Effect of inhibition of interleukin-12/23 by ustekinumab on the expression of leptin and leptin receptor in human THP-1 macrophages. Clin. Exp. Dermatol. 41 308– 311. 10.1111/ced.12699 26095599 PMC4685020 · DOI

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Cited by

Sorted by citations

Authors
Francisco, V., Pino, J., Campos-Cabaleiro, V., Ruiz-Fernández, C., Mera, A., Gonzalez-Gay, M. A., Gómez, R., & Gualillo, O.
Affiliations
  • Instituto de Investigación Sanitaria de Santiago (ES)
  • Complejo Hospitalario Universitario de Santiago (ES)
Corresponding author
Francisco, Vera
ORCID
Venue
Frontiers in Physiology
Publisher
Frontiers Media SA
Published
2018-06-01
Volume
9
Pages
640-640
ISSN
1664-042X (ISSN-L)
DOI
10.3389/fphys.2018.00640
PMC
PMC5992476
OpenAlex
W2799348059
Cited by
411
References
16
Citations by year
2026: 19 · 2025: 41 · 2024: 48 · 2023: 43 · 2022: 67 · 2021: 75 · 2020: 66 · 2019: 44 · 2018: 7 · 2017: 1
FWCI
6.89
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Physiology (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • UCrea (University of Cantabria) (publishedVersion, other-oa)
  • LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • European Commission (H2020 Program, PI16/01870, H2020, CP15/00007, 734899)
  • Xunta de Galicia (PIE13/00024,)
  • Horizon 2020 Framework Programme (734899)
  • Research Executive Agency (734899)
  • Instituto de Salud Carlos III (PI16/, 734899, PI14/00016, PIE13/00024, CP15/00007, PI14/, RD16/0012/0014, RD16/0012, PI16/01870, H2020, PI17/00409, 00016)
  • Servicio Gallego de Salud
Topics
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
  • Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
Keywords
leptin, obesity, adipose tissue, adipokines, immunometabolism, low-grade inflammation, energy metabolism, leptin receptor, innate immunity, adaptive immunity, autoimmune disease, inflammatory rheumatic diseases, metabolic disorders

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