Abstract
Objective
This study aimed to evaluate the relationship between the circulating serum leptin level and rheumatoid arthritis (RA) and to establish a correlation between serum leptin levels and RA activity.
Methods
We searched the PUBMED, EMBASE, and Cochrane databases. A meta-analysis was performed, comparing the serum/plasma leptin levels in patients with RA and healthy controls. Correlation coefficients between serum leptin level and either disease activity score 28 (DAS28) or C‑reactive protein (CRP) in RA patients were also examined.
Results
Thirteen studies with a total of 648 RA patients and 426 controls were included in this meta-analysis. Circulating leptin level was significantly higher in the RA group than in the control group (SMD = 1.056, 95 % CI = 0.647–1.465, p = 4.2 × 10−7). In addition, stratification by ethnicity showed a significantly elevated leptin level in the RA group in Caucasian, Turkish, and Arab populations (SMD = 0.813, 95 % CI = 0.137–1.490, p = 0.018, SMD = 0.981, 95 % CI = 0.307–1.655, p = 0.004, and SMD = 1.469, 95 % CI = 0.443–2.495, p = 0.005 respectively). A meta-analysis of correlation coefficients showed a small but significantly positive correlation between the circulating leptin level and either DAS28 (correlation coefficient = 0.275, 95 % CI = 0.076–0.452, p = 0.007) or CRP (correlation coefficient = 0.274, 95 % CI = 0.068–0.458, p = 0.010).
Conclusions
Our meta-analysis demonstrated that the circulating leptin level is significantly higher in patients with RA and that a small but significantly positive correlation exists between leptin levels and RA activity.
Zusammenfassung
Ziel
Ziel der Studie war es, den Zusammenhang zwischen zirkulierendem Serumleptinspiegel und rheumatischer Arthritis (RA) zu untersuchen und eine Korrelation zwischen Serumleptinspiegeln und der RA-Aktivität festzustellen.
Methoden
Wir durchsuchten die Datenbanken PUBMED, EMBASE und Cochrane. Eine Metaanalyse wurde durchgeführt, bei der die Serum-/Plasmaleptinspiegel bei RA-Patienten und bei gesunden Kontrollgruppen untersucht wurden. Der Korrelationskoeffizient zwischen Serumleptinspiegel und entweder der Krankheitsaktivität 28 (disease activity score; DAS28) oder C‑reaktivem Protein (CRP) bei RA-Patienten wurden ebenfalls untersucht.
Ergebnisse
Dreizehn Studien mit insgesamt 648 Patienten und 426 Kontrollpersonen wurde in die Metaanalyse einbezogen. Der zirkulierende Leptinspiegel war in der RA-Gruppe signifikant höher als in der Kontrollgruppe (SMD = 1,056, 95 % CI = 0,647–1,465, p = 4,2 × 10− 7). Die Schichtung nach Ethnie zeigte einen signifikant erhöhten Leptinspiegel in der RA-Gruppe bei der hellhäutigen, türkischen und arabischen Bevölkerung (SMD = 0,813, 95 % CI = 0,137–1,490, p = 0,018, SMD = 0,981, 95 % CI = 0,307–1,655, p = 0,004 bzw. SMD = 1,469, 95 % CI = 0,443–2,495, p = 0,005). Eine Metaanalyse der Korrelationskoeffizienten zeigte eine kleine, aber signifikant positive Korrelation zwischen dem zirkulierendem Leptinspiegel und entweder DAS28 (Korrelationskoeffizient = 0,275, 95 % CI = 0,076–0,452, p = 0,007) oder CRP (Korrelationskoeffizient = 0,274, 95 % CI = 0,068–0,458, p = 0,010).
Zusammenfassung
Unsere Metaanalyse konnte darlegen, dass der zirkulierende Leptinspiegel bei Patienten mit RA signifikant höher ist und dass eine kleine aber signifikant positive Korrelation zwischen Leptinspiegeln und der RA-Aktivität besteht.
Similar content being viewed by others
References
Harris ED Jr (1990) Rheumatoid arthritis. Pathophysiology and implications for therapy. N Engl J Med 322(18):1277–1289
Choi SJ, Rho YH, Ji JD, Song GG, Lee YH (2006) Genome scan meta-analysis of rheumatoid arthritis. Rheumatology (Oxford) 45(2):166–170
Kelesidis T, Kelesidis I, Chou S, Mantzoros CS (2010) Narrative review: the role of leptin in human physiology: emerging clinical applications. Ann Intern Med 152(2):93–100
Conde J, Scotece M, Gómez R, López V, Gómez-Reino JJ, Lago F et al (2011) Adipokines: biofactors from white adipose tissue. A complex hub among inflammation, metabolism, and immunity. Biofactors 37(6):413–420
Fantuzzi G, Faggioni R (2000) Leptin in the regulation of immunity, inflammation, and hematopoiesis. J Leukoc Biol 68(4):437–446
Fernández-Riejos P, Najib S, Santos-Alvarez J, Martín-Romero C, Pérez-Pérez A, González-Yanes C et al (2010) Role of leptin in the activation of immune cells. Mediat Inflamm 2010:568343
Gabay C, Dreyer M, Pellegrinelli N, Chicheportiche R, Meier CA (2001) Leptin directly induces the secretion of interleukin 1 receptor antagonist in human monocytes. J Clin Endocrinol Metab 86(2):783–791
Li HM, Zhang TP, Leng RX, Li XP, Li XM, Pan HF (2015) Plasma/serum leptin levels in patients with systemic lupus erythematosus: a meta-analysis. Arch Med Res 46(7):551–556
Matarese G, Sanna V, Di Giacomo A, Lord GM, Howard JK, Bloom SR et al (2001) Leptin potentiates experimental autoimmune encephalomyelitis in SJL female mice and confers susceptibility to males. Eur J Immunol 31(5):1324–1332
Abdalla M, Effat D, Sheta M, Hamed WE (2014) Serum leptin levels in rheumatoid arthritis and relationship with disease activity. Egypt Rheumatol 36(1):1–5
Olama SM, Senna MK, Elarman M (2012) Synovial/serum leptin ratio in rheumatoid arthritis: the association with activity and erosion. Rheumatol Int 32(3):683–690
Allam A, Radwan A (2012) The relationship of serum leptin levels with disease activity in Egyptian patients with rheumatoid arthritis. Egypt Rheumatol 34(4):185–190
Ismail F, HA-h A, Ibrahim HM (2011) Possible role of leptin, and tumor necrosis factor-alpha in hypoandrogenicity in patients with early rheumatoid arthritis. Egypt Rheumatol 33(4):209–215
El-Batch MM, Zakaria SS, Farouk G, El Saadany H, Selim M (2010) Changes in visfatin, adiponectin, leptin and ghrelin levels in patients with rheumatoid arthritis and their correlation with disease activity. Turkish J Biochem Biyokimya Dergisi 35(1):50–57
Seven A, Guzel S, Aslan M, Hamuryudan V (2009) Serum and synovial fluid leptin levels and markers of inflammation in rheumatoid arthritis. Rheumatol Int 29(7):743–747
Rho YH, Solus J, Sokka T, Oeser A, Chung CP, Gebretsadik T et al (2009) Adipocytokines are associated with radiographic joint damage in rheumatoid arthritis. Arthritis Rheum 60(7):1906–1914
Turhanoğlu AD, Özmen Ş, Ogün C, Kaplan A (2009) Plasma resistin and leptin levels in overweight and lean patients with rheumatoid arthritis. Turk J Med Sci 39(3):447–451
Hizmetli S, Kisa M, Gokalp N, Bakici MZ (2007) Are plasma and synovial fluid leptin levels correlated with disease activity in rheumatoid arthritis? Rheumatol Int 27(4):335–338
Gunaydin R, Kaya T, Atay A, Olmez N, Hur A, Koseoglu M (2006) Serum leptin levels in rheumatoid arthritis and relationship with disease activity. South Med J Birm Ala 99(10):1078
Otero M, Lago R, Gomez R, Lago F, Dieguez C, Gomez-Reino JJ et al (2006) Changes in plasma levels of fat-derived hormones adiponectin, leptin, resistin and visfatin in patients with rheumatoid arthritis. Ann Rheum Dis 65(9):1198–1201
Popa C, Netea MG, Radstake TR, van Riel PL, Barrera P, van der Meer JW (2005) Markers of inflammation are negatively correlated with serum leptin in rheumatoid arthritis. Ann Rheum Dis 64(8):1195–1198
Bokarewa M, Bokarew D, Hultgren O, Tarkowski A (2003) Leptin consumption in the inflamed joints of patients with rheumatoid arthritis. Ann Rheum Dis 62(10):952–956
Lee YH, Woo JH, Choi SJ, Ji JD, Song GG (2010) Associations between osteoprotegerin polymorphisms and bone mineral density: a meta-analysis. Mol Biol Rep 37(1):227–234
Lee YH, Rho YH, Choi SJ, Ji JD, Song GG (2007) PADI4 polymorphisms and rheumatoid arthritis susceptibility: a meta-analysis. Rheumatol Int 27(9):827–833
Lee YH, Woo JH, Choi SJ, Ji JD, Song GG (2010) Induction and maintenance therapy for lupus nephritis: a systematic review and meta-analysis. Lupus 19(6):703–710
Hozo SP, Djulbegovic B, Hozo I (2005) Estimating the mean and variance from the median, range, and the size of a sample. BMC Med Res Methodol 5:13
Wells GA, Shea B, O’Connell D, Peterson J, Welch V, Losos M et al (2011) The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Ottawa Health Research Institute, Ottawa. http://www.ohri.ca/programs/clinical_epidemiology/oxford.htm
Egger M, Smith GD, Phillips AN (1997) Meta-analysis: principles and procedures. BMJ 315(7121):1533–1537
DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7(3):177–188
Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21(11):1539–1558
Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315(7109):629–634
Aminzadeh MA, Pahl MV, Barton CH, Doctor NS, Vaziri ND (2009) Human uraemic plasma stimulates release of leptin and uptake of tumour necrosis factor-alpha in visceral adipocytes. Nephrol Dial Transplant 24(12):3626–3631
Gunaydin R, Kaya T, Atay A, Olmez N, Hur A, Koseoglu M (2006) Serum leptin levels in rheumatoid arthritis and relationship with disease activity. South Med J 99(10):1078–1083
Otero M, Lago R, Gomez R, Dieguez C, Lago F, Gómez-Reino J et al (2006) Towards a pro-inflammatory and immunomodulatory emerging role of leptin. Rheumatology 45(8):944–950
Iikuni N, Lam QL, Lu L, Matarese G, La Cava A (2008) Leptin and Inflammation. Curr Immunol Rev 4(2):70–79
Lord GM, Matarese G, Howard JK, Baker RJ, Bloom SR, Lechler RI (1998) Leptin modulates the T-cell immune response and reverses starvation-induced immunosuppression. Nature 394(6696):897–901
White DW, Kuropatwinski KK, Devos R, Baumann H, Tartaglia LA (1997) Leptin receptor (OB-R) signaling. Cytoplasmic domain mutational analysis and evidence for receptor homo-oligomerization. J Biol Chem 272(7):4065–4071
Muraoka S, Kusunoki N, Takahashi H, Tsuchiya K, Kawai S (2013) Leptin stimulates interleukin-6 production via janus kinase 2/signal transducer and activator of transcription 3 in rheumatoid synovial fibroblasts. Clin Exp Rheumatol 31(4):589–595
Alshaker H, Wang Q, Frampton AE, Krell J, Waxman J, Winkler M et al (2015) Sphingosine kinase 1 contributes to leptin-induced STAT3 phosphorylation through IL-6/gp130 transactivation in oestrogen receptor-negative breast cancer. Breast Cancer Res Treat 149(1):59–67
Tian G, Liang JN, Wang ZY, Zhou D (2014) Emerging role of leptin in rheumatoid arthritis. Clin Exp Immunol 177(3):557–570
Fazeli M, Zarkesh-Esfahani H, Wu Z, Maamra M, Bidlingmaier M, Pockley AG et al (2006) Identification of a monoclonal antibody against the leptin receptor that acts as an antagonist and blocks human monocyte and T cell activation. J Immunol Methods 312(1–2):190–200
Iliopoulos D, Malizos KN, Tsezou A (2007) Epigenetic regulation of leptin affects MMP-13 expression in osteoarthritic chondrocytes: possible molecular target for osteoarthritis therapeutic intervention. Ann Rheum Dis 66(12):1616–1621
Feng GS (2006) Shp2 as a therapeutic target for leptin resistance and obesity. Expert Opin Ther Targets 10(1):135–142
Soebiyanto RP, Sreenath SN, Qu CK, Loparo KA, Bunting KD (2007) Complex systems biology approach to understanding coordination of JAK-STAT signaling. Biosystems 90(3):830–842
Toussirot É, Michel F, Binda D, Dumoulin G (2015) The role of leptin in the pathophysiology of rheumatoid arthritis. Life Sci 140:29–36
Acknowledegment
This study was supported in part by a grant from the Korea Healthcare technology R&D Project, Ministry for Health and Welfare, Republic of Korea (HI13C2124).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflicts of interest
Y. H. Lee and S.-C. Bae states that there are no conflicts of interest.
The accompanying manuscript does not include studies on humans or animals.
Additional information
Redaktion
U. Müller-Ladner, Bad Nauheim
U. Lange, Bad Nauheim
Rights and permissions
About this article
Cite this article
Lee, Y.H., Bae, S. Circulating leptin level in rheumatoid arthritis and its correlation with disease activity: a meta-analysis. Z Rheumatol 75, 1021–1027 (2016). https://doi.org/10.1007/s00393-016-0050-1
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00393-016-0050-1