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 Table of Contents  
EDITORIAL
Year : 2021  |  Volume : 16  |  Issue : 1  |  Page : 1-2

Leptin and Lupus..........the Story Continues!


Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India

Date of Submission25-Feb-2021
Date of Acceptance01-Mar-2021
Date of Web Publication23-Mar-2021

Correspondence Address:
Dr. Durga Prasanna Misra
Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow - 226 014, Uttar Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/injr.injr_47_21

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How to cite this article:
Misra DP. Leptin and Lupus..........the Story Continues!. Indian J Rheumatol 2021;16:1-2

How to cite this URL:
Misra DP. Leptin and Lupus..........the Story Continues!. Indian J Rheumatol [serial online] 2021 [cited 2021 Apr 15];16:1-2. Available from: https://www.indianjrheumatol.com/text.asp?2021/16/1/1/311766



Adipokines were initially recognized for their role in maintaining homeostasis of glucose and energy metabolism. Well-recognized adipokines are leptin and adiponectin. Recent literature has elucidated the role of adipokines in immune-mediated processes. The recent article by Balaji et al.[1] evaluates the association between the pro-inflammatory adipokine leptin and systemic lupus erythematosus (SLE). Patients with SLE enrolled in the study were carefully selected such that their body mass index was between 18 and 30 kg/m2, since perturbations in body weight can per se affect levels of adipokines. The authors identified higher levels of leptin in patients with SLE when compared with healthy controls. Correlations of weak to moderate magnitude, although statistically significant, were found between leptin levels and body mass index, serum uric acid (positive correlation), and serum high-density lipoprotein cholesterol (negative correlation). Higher proportions of patients with renal lupus had elevated leptin levels when compared with nonrenal lupus.[1] Limitations of the study were lack of formal assessment of study power and sample size a priori. The association of leptin levels with various clinical manifestations of lupus were likely underpowered.

The study reiterates previously described finding of higher leptin levels in patients with lupus. A systematic review with meta-analysis of 18 studies (1333 lupus patients and 1048 healthy controls) confirmed higher levels of leptin in lupus than in healthy controls.[2] Polymorphisms in the gene encoding leptin receptor have also been associated with increased risk of lupus.[3] The mechanisms by which leptin might promote lupus pathogenesis have been explored in preclinical models of SLE. Leptin has been demonstrated to enhance autoantibody production and induce renal injury.[4] Leptin also adversely affects the balance between pro- and anti-inflammatory T-lymphocyte populations. Leptin induces activation of effector T-cells while suppressing regulatory T-lymphocytes.[4],[5] Leptin also promotes T helper 17 cell and natural killer cell activity.[6]

It is now recognized that cardiovascular risk is increased in patients with rheumatic diseases. Many inflammatory rheumatic diseases have at least equivalent risk of cardiovascular disease (CVD) as diabetes mellitus. Lupus particularly associates with markedly increased risk of cardiovascular events, which occur at a much younger age despite the gender predominance of lupus in females (whose hormonal milieu protects against cardiovascular events in the premenopausal period).[7] Adipokines per se associate with cardiovascular risk. Leptin has been proposed to be pro-atherogenic, whereas its counterpart adipokine adiponectin retards atherosclerosis. Leptin levels are higher in obese individuals, who are at a higher risk of CVD. One of the mechanisms by which leptin levels are increased is leptin resistance. Leptin resistance associates with insulin resistance (thereby, hyperinsulinemia), which might be a mechanism associating increased CVD risk with hyperleptinemia.[8],[9] Leptin has been proposed to increase the systemic inflammatory milieu underlying atherosclerosis. Higher levels of leptin also associate with sympathetic hyperactivity. Endothelial dysfunction has also been associated with increased leptin levels.[10] Epicardial fat thickness, which has been associated with increased cardiovascular risk, is also associated with increased leptin levels.[11],[12] However, a causal association between leptin and CVD has yet to be conclusively established. A large cohort of patients with leptin levels assessed at baseline did not demonstrate a significantly higher risk of cardiovascular events with increased leptin levels when followed up over a median 7.6 years.[13] The role of therapies targeting higher leptin levels in patients at increased CVD risk also requires exploration.[8] Nevertheless, the common association of higher leptin levels with CVD risk factors and with lupus (which per se associates with higher CVD risk) merits further exploration of leptin and downstream pathways in the modulation of cardiovascular risk in lupus.



 
  References Top

1.
Balaji C, Saranya C, Bhuvanesh M, Ramesh R, Sriram S, Rajeswari S. Serum adipokine leptin levels in systemic lupus erythematosus patients and its correlation with clinical manifestations and disease activity – A cross-sectional study from a tertiary care center. Indian J Rheumatol 2021;16:3-8.  Back to cited text no. 1
  [Full text]  
2.
Lee YH, Song GG. Association between circulating leptin levels and systemic lupus erythematosus: An updated meta-analysis. Lupus 2018 27:428-35.  Back to cited text no. 2
    
3.
Afifi AE, Shaat RM, Gharbia OM, Elhanafy M, Hasan AS. Role of serum leptin levels and leptin receptor gene polymorphisms in systemic lupus erythematosus. Clin Rheumatol 2020;39:3465-72.  Back to cited text no. 3
    
4.
Lourenço EV, Liu A, Matarese G, La Cava A. Leptin promotes systemic lupus erythematosus by increasing autoantibody production and inhibiting immune regulation. Proc Natl Acad Sci U S A 2016;113:10637-42.  Back to cited text no. 4
    
5.
Margiotta D, Navarini L, Vadacca M, Basta F, Lo Vullo M, Pignataro F, et al. Relationship between leptin and regulatory T cells in systemic lupus erythematosus: Preliminary results. Eur Rev Med Pharmacol Sci 2016;20:636-41.  Back to cited text no. 5
    
6.
Xu WD, Zhang M, Zhang YJ, Liu SS, Pan HF, Ye DQ. Association between leptin and systemic lupus erythematosus. Rheumatol Int 2014;34:559-63.  Back to cited text no. 6
    
7.
Nurmohamed MT, Heslinga M, Kitas GD. Cardiovascular comorbidity in rheumatic diseases. Nat Rev Rheumatol 2015;11:693-704.  Back to cited text no. 7
    
8.
Martin SS, Qasim A, Reilly MP. Leptin resistance: A possible interface of inflammation and metabolism in obesity-related cardiovascular disease. J Am Coll Cardiol 2008;52:1201-10.  Back to cited text no. 8
    
9.
Patel SB, Reams GP, Spear RM, Freeman RH, Villarreal D. Leptin: Linking obesity, the metabolic syndrome, and cardiovascular disease. Curr Hypertens Rep 2008;10:131-7.  Back to cited text no. 9
    
10.
Knudson JD, Payne GA, Borbouse L, Tune JD. Leptin and mechanisms of endothelial dysfunction and cardiovascular disease. Curr Hypertens Rep 2008;10:434-9.  Back to cited text no. 10
    
11.
.Kaneda H, Nakajima T, Haruyama A, Shibasaki I, Hasegawa T, Sawaguchi T, et al. Association of serum concentrations of irisin and the adipokines adiponectin and leptin with epicardial fat in cardiovascular surgery patients. PLoS One 2018;13:e0201499.  Back to cited text no. 11
    
12.
D'Marco L, Puchades MJ, Gorriz JL, Romero-Parra M, Lima-Martínez M, Soto C, et al. Epicardial adipose tissue, adiponectin and leptin: A potential source of cardiovascular risk in chronic kidney disease. Int J Mol Sci 2020;21:978.  Back to cited text no. 12
    
13.
Martin SS, Blaha MJ, Muse ED, Qasim AN, Reilly MP, Blumenthal RS, et al. Leptin and incident cardiovascular disease: The multi-ethnic study of atherosclerosis (MESA). Atherosclerosis 2015;239:67-72.  Back to cited text no. 13
    




 

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