|Year : 2021 | Volume
| Issue : 1 | Page : 1-2
Leptin and Lupus..........the Story Continues!
Durga Prasanna Misra
Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
|Date of Submission||25-Feb-2021|
|Date of Acceptance||01-Mar-2021|
|Date of Web Publication||23-Mar-2021|
Dr. Durga Prasanna Misra
Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow - 226 014, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Misra DP. Leptin and Lupus..........the Story Continues!. Indian J Rheumatol 2021;16:1-2
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. 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. 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. Polymorphisms in the gene encoding leptin receptor have also been associated with increased risk of lupus. 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. 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., Leptin also promotes T helper 17 cell and natural killer cell activity.
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). 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., 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. Epicardial fat thickness, which has been associated with increased cardiovascular risk, is also associated with increased leptin levels., 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. The role of therapies targeting higher leptin levels in patients at increased CVD risk also requires exploration. 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.
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