Leptin: Molecular mechanisms, systemic pro-inflammatory effects, and clinical implications;Leptina: Mecanismos moleculares, efeitos próinflamatórios sistêmicos e implicações clínicas

Arquivos Brasileiros de Endocrinologia e Metabologia

Volumn 56, Issue 9, 2012, Pages 597-607

  Paz Filho, Gilberto ^a   Mastronardi, Claudio ^a   Franco, Carina Bertoldi ^b   Wang, Kevin Boyang ^c   Wong, Ma Li ^a   Licinio, Julio ^a  

^a Biology and Environment   (Australia)

^b The Australian National University   (Australia)

^c MONASH UNIVERSITY   (Australia)

Author keywords

Cytokines; Immunity; Inflammation; Leptin

Indexed keywords

AUTACOID; CYTOKINE; IMMUNOLOGIC FACTOR; LEPTIN; LEPTIN RECEPTOR;

ADAPTIVE IMMUNITY; ANIMAL; CHRONIC DISEASE; DISEASE MODEL; HUMAN; IMMUNOLOGY; INFLAMMATION; METABOLISM; PHYSIOLOGY; REVIEW;

ADAPTIVE IMMUNITY; ANIMALS; CHRONIC DISEASE; CYTOKINES; DISEASE MODELS, ANIMAL; HUMANS; IMMUNOLOGIC FACTORS; INFLAMMATION; INFLAMMATION MEDIATORS; LEPTIN; RECEPTORS, LEPTIN;

EID: 84872774545     PISSN: 00042730     EISSN: 16779487     Source Type: Journal    
DOI: 10.1590/S0004-27302012000900001     Document Type: Review

References (60)

1. Kershaw EE, Flier JS. Adipose tissue as an endocrine organ. J Clin Endocrinol Metab. 2004;89:2548-56.
2. Wajchenberg BL, Nery M, Cunha MR, Silva ME. Adipose tissue at the crossroads in the development of the metabolic syndrome, inflammation and atherosclerosis. Arq Bras Endocrinol Metabol. 2009;53:145-50.
3. Friedman JM, Halaas JL. Leptin and the regulation of body weight in mammals. Nature. 1998;395:763-70.
4. Kelesidis T, Kelesidis I, Chou S, Mantzoros CS. Narrative review: the role of leptin in human physiology: emerging clinical applications. Ann Intern Med. 2012;152:93-100.
5. Boguszewski CL, Paz-Filho G, Velloso LA. Neuroendocrine body weight regulation: integration between fat tissue, gastrointestinal tract, and the brain. Endokrynologia Polska. 2011;61:194-206.
6. Paz-Filho G, Mastronardi C, Delibasi T, Wong ML, Licinio J. Congenital leptin deficiency: diagnosis and effects of leptin replacement therapy. Arq Bras Endocrinol Metabol. 2010;54:690-7.
7. Paz-Filho G, Wong ML, Licinio J. Ten years of leptin replacement therapy. Obes Rev. 2011;12:e315-23.
8. Conde J, Scotece M, Gomez R, Lopez V, Gomez-Reino JJ, Lago F, et al. Adipokines: biofactors from white adipose tissue. A complex hub among inflammation, metabolism, and immunity. Biofactors. 2011;37:413-20.
9. Maury E, Brichard SM. Adipokine dysregulation, adipose tissue inflammation and metabolic syndrome. Mol Cell Endocrinol. 2010;314:1-16.
10. Bernotiene E, Palmer G, Gabay C. The role of leptin in innate and adaptive immune responses. Arthritis Res Ther. 2006;8:217.
11. La Cava A, Matarese G. The weight of leptin in immunity. Nat Rev Immunol. 2004;4:371-9.
12. Tartaglia LA, Dembski M, Weng X, Deng N, Culpepper J, Devos R, et al. Identification and expression cloning of a leptin receptor, OB-R. Cell. 1995;83:1263-71.
13. Madej T, Boguski MS, Bryant SH. Threading analysis suggests that the obese gene product may be a helical cytokine. FEBS letters. 1995;373:13-8.
14. Ghilardi N, Ziegler S, Wiestner A, Stoffel R, Heim MH, Skoda RC. Defective STAT signaling by the leptin receptor in diabetic mice. Proc Natl Acad Sci U S A. 1996;93:6231-5.
15. Donato J Jr, Frazao R, Elias CF. The PI3K signaling pathway mediates the biological effects of leptin. Arq Bras Endocrinol Metabol. 2010;54:591-602.
16. Banks AS, Davis SM, Bates SH, Myers MG. Activation of downstream signals by the long form of the leptin receptor. J Biol Chem. 2000;275:14563-72.
17. Torii S, Nakayama K, Yamamoto T, Nishida E. Regulatory mechanisms and function of ERK MAP kinases. J Biochem. 2004;136:557-61.
18. Munzberg H, Bjornholm M, Bates SH, Myers MG Jr. Leptin receptor action and mechanisms of leptin resistance. Cell Mol Life Sci. 2005;62:642-52.
19. Fruhbeck G. Intracellular signalling pathways activated by leptin. Biochem J. 2006;393:7-20.
20. Starr R, Willson TA, Viney EM, Murray LJ, Rayner JR, Jenkins BJ, et al. A family of cytokine-inducible inhibitors of signalling. Nature. 1997;387:917-21.
21. Bjorbak C, Lavery HJ, Bates SH, Olson RK, Davis SM, Flier JS, et al. SOCS3 mediates feedback inhibition of the leptin receptor via Tyr985. J Biol Chem. 2000;275:40649-57.
22. Bjorbaek C, Elmquist JK, Frantz JD, Shoelson SE, Flier JS. Identification of SOCS-3 as a potential mediator of central leptin resistance. Molecular Cell. 1998;1:619-25.
23. Mori H, Hanada R, Hanada T, Aki D, Mashima R, Nishinakamura H, et al. Socs3 deficiency in the brain elevates leptin sensitivity and confers resistance to diet-induced obesity. Nat Med. 2004;10:739-43.
24. Myers MP, Andersen JN, Cheng A, Tremblay ML, Horvath CM, Parisien JP, et al. TYK2 and JAK2 are substrates of protein-tyrosine phosphatase 1B. J Biol Chem. 2001;276:47771-4.
25. Bence KK, Delibegovic M, Xue B, Gorgun CZ, Hotamisligil GS, Neel BG, et al. Neuronal PTP1B regulates body weight, adiposity and leptin action. Nat Med. 2006;12:917-24.
26. Zabolotny JM, Bence-Hanulec KK, Stricker-Krongrad A, Haj F, Wang Y, Minokoshi Y, et al. PTP1B regulates leptin signal transduction in vivo. Dev Cell. 2002;2:489-95.
27. Batra A, Okur B, Glauben R, Erben U, Ihbe J, Stroh T, et al. Leptin: a critical regulator of CD4+ T-cell polarization in vitro and in vivo. Endocrinology. 2010;151:56-62.
28. Matarese G, Procaccini C, De Rosa V, Horvath TL, La Cava A. Regulatory T cells in obesity: the leptin connection. Trends Mol Med. 2010;16:247-56.
29. Lord GM, Matarese G, Howard JK, Baker RJ, Bloom SR, Lechler RI. Leptin modulates the T-cell immune response and reverses starvation-induced immunosuppression. Nature. 1998;394:897-901.
30. Iikuni N, Lam QL, Lu L, Matarese G, La Cava A. Leptin and inflammation. Curr Immunol Rev. 2008;4:70-9.
31. Dixit VD, Mielenz M, Taub DD, Parvizi N. Leptin induces growth hormone secretion from peripheral blood mononuclear cells via a protein kinase C-and nitric oxide-dependent mechanism. Endocrinology. 2003;144:5595-603.
32. Rafail S, Ritis K, Schaefer K, Kourtzelis I, Speletas M, Doumas M, et al. Leptin induces the expression of functional tissue factor in human neutrophils and peripheral blood mononuclear cells through JAK2-dependent mechanisms and TNFalpha involvement. Thromb Res. 2008;122:366-75.
33. Steiner AA, Romanovsky AA. Leptin: at the crossroads of energy balance and systemic inflammation. Prog Lipid Res. 2007;46:89-107.
34. Otero M, Lago R, Gomez R, Dieguez C, Lago F, Gomez-Reino J, et al. Towards a pro-inflammatory and immunomodulatory emerging role of leptin. Rheumatology (Oxford). 2006;45:944-50.
35. Martin-Romero C, Santos-Alvarez J, Goberna R, Sanchez-Margalet V. Human leptin enhances activation and proliferation of human circulating T lymphocytes. Cell Immunol. 2000;199:15-24.
36. Fernandez-Riejos P, Najib S, Santos-Alvarez J, Martin-Romero C, Perez-Perez A, Gonzalez-Yanes C, et al. Role of leptin in the activation of immune cells. Mediators Inflamm. 2010;2010:568343.
37. Howard JK, Lord GM, Matarese G, Vendetti S, Ghatei MA, Ritter MA, et al. Leptin protects mice from starvation-induced lymphoid atrophy and increases thymic cellularity in ob/ob mice. J Clin Invest. 1999;104:1051-9.
38. Tschop J, Nogueiras R, Haas-Lockie S, Kasten KR, Castaneda TR, Huber N, et al. CNS leptin action modulates immune response and survival in sepsis. J Neurosci. 2010;30:6036-47.
39. Siegmund B, Lehr HA, Fantuzzi G. Leptin: a pivotal mediator of intestinal inflammation in mice. Gastroenterology. 2002;122:2011-25.
40. Farooqi IS, Matarese G, Lord GM, Keogh JM, Lawrence E, Agwu C, et al. Beneficial effects of leptin on obesity, T cell hyporesponsiveness, and neuroendocrine/metabolic dysfunction of human congenital leptin deficiency. J Clin Invest. 2002;110:1093-103.
41. Farooqi IS, Wangensteen T, Collins S, Kimber W, Matarese G, Keogh JM, et al. Clinical and molecular genetic spectrum of congenital deficiency of the leptin receptor. N Engl J Med. 2007;356:237-47.
42. Paz-Filho GJ, Delibasi T, Erol HK, Wong ML, Licinio J. Cellular immunity before and after leptin replacement therapy. J Pediatr Endocrinol Metab. 2009;22:1069-74.
43. Gibson WT, Farooqi IS, Moreau M, DePaoli AM, Lawrence E, O'Rahilly S, et al. Congenital leptin deficiency due to homozygosity for the Delta133G mutation: report of another case and evaluation of response to four years of leptin therapy. J Clin Endocrinol Metab. 2004;89:4821-6.
44. Tanaka M, Suganami T, Kim-Saijo M, Toda C, Tsuiji M, Ochi K, et al. Role of central leptin signaling in the starvation-induced alteration of B-cell development. J Neurosci. 2011;31:8373-80.
45. Chan JL, Moschos SJ, Bullen J, Heist K, Li X, Kim YB, et al. Recombinant methionyl human leptin administration activates signal transducer and activator of transcription 3 signaling in peripheral blood mononuclear cells in vivo and regulates soluble tumor necrosis factor-alpha receptor levels in humans with relative leptin deficiency. J Clin Endocrinol Metab. 2005;90:1625-31.
46. Oral EA, Javor ED, Ding L, Uzel G, Cochran EK, Young JR, et al. Leptin replacement therapy modulates circulating lymphocyte subsets and cytokine responsiveness in severe lipodystrophy. J Clin Endocrinol Metab. 2006;91:621-8.
47. Zhang H, Zhang C. Adipose "talks" to distant organs to regulate insulin sensitivity and vascular function. Obesity (Silver Spring). 2010;18:2071-6.
48. Rasouli N, Kern PA. Adipocytokines and the metabolic complications of obesity. J Clin Endocrinol Metab. 2008;93:S64-73.
49. Anfossi G, Russo I, Doronzo G, Pomero A, Trovati M. Adipocytokines in atherothrombosis: focus on platelets and vascular smooth muscle cells. Mediators Inflamm. 2010;2010:174341.
50. Wallace AM, McMahon AD, Packard CJ, Kelly A, Shepherd J, Gaw A, et al. Plasma leptin and the risk of cardiovascular disease in the west of Scotland coronary prevention study (WOSCOPS). Circulation. 2001;104:3052-6.
51. Esteghamati A, Khalilzadeh O, Anvari M, Rashidi A, Mokhtari M, Nakhjavani M. Association of serum leptin levels with homeostasis model assessment-estimated insulin resistance and metabolic syndrome: the key role of central obesity. Metab Syndr Relat Disord. 2009;7:447-52.
52. Paz-Filho GJ, Volaco A, Suplicy HL, Radominski RB, Boguszewski CL. Decrease in leptin production by the adipose tissue in obesity associated with severe metabolic syndrome. Arq Bras Endocrinol Metabol. 2009;53:1088-95.
53. Hekerman P, Zeidler J, Korfmacher S, Bamberg-Lemper S, Knobelspies H, Zabeau L, et al. Leptin induces inflammation-related genes in RINm5F insulinoma cells. BMC Mol Biol. 2007;8:41.
54. Bornstein SR, Licinio J, Tauchnitz R, Engelmann L, Negrao AB, Gold P, et al. Plasma leptin levels are increased in survivors of acute sepsis: associated loss of diurnal rhythm, in cortisol and leptin secretion. J Clin Endocrinol Metab. 1998;83:280-3.
55. Fantuzzi G. Adipose tissue, adipokines, and inflammation. J Allergy Clin Immunol. 2005;115:911-9.
56. Gomez R, Conde J, Scotece M, Gomez-Reino JJ, Lago F, Gualillo O. What's new in our understanding of the role of adipokines in rheumatic diseases? Nat Rev Rheumatol. 2011;7:528-36.
57. Kruger AJ, Yang C, Lipson KL, Pino SC, Leif JH, Hogan CM, et al. Leptin treatment confers clinical benefit at multiple stages of virally induced type 1 diabetes in BB rats. Autoimmunity. 2011;44:137-48.
58. Konturek PC, Jaworek J, Maniatoglou A, Bonior J, Meixner H, Konturek SJ, et al. Leptin modulates the inflammatory response in acute pancreatitis. Digestion. 2002;65:149-60.
59. Cakir B, Bozkurt A, Ercan F, Yegen BC. The anti-inflammatory effect of leptin on experimental colitis: involvement of endogenous glucocorticoids. Peptides. 2004;25:95-104.
60. Bokarewa M, Bokarew D, Hultgren O, Tarkowski A. Leptin consumption in the inflamed joints of patients with rheumatoid arthritis. Ann Rheum Dis. 2003;62:952-6.