Leptin, an adipokine secreted by fat tissue, plays a dual role in regulating energy balance and modulating immune function. Now, a recent study published in Medicine (Baltimore) revealed that obesity-related dysregulation in circulating adipokines might play a potential role in the pathogenesis of systemic lupus erythematosus (SLE). The cross-sectional study examined the association between serum leptin levels, body mass index (BMI), and disease activity in 221 Thai women with SLE.
The study population demonstrated that 147 patients (66.52%) maintained normal weight (BMI 18.5-24.9 kg/m²), while 51 patients (23.08%) were overweight (BMI 25-29.9 kg/m²), and 23 patients (10.41%) were obese (BMI ≥30 kg/m²). Obese patients exhibited significantly higher rates of hypertension, dyslipidemia, diabetes mellitus, and reduced glomerular filtration rate compared to normal-weight and overweight categories. The analysis revealed a positive correlation between BMI and increased SLE Disease Activity Index 2000 (cSLEDAI-2K) scores over the preceding year (r = 0.21, P = 0.002).
Serum leptin analysis was performed in 80 patients, demonstrating strong positive correlation with BMI (r = 0.69, P < 0.001). Elevated leptin levels showed significant associations with neuropsychiatric manifestations (r = 0.24, P = 0.04) and hematologic manifestations (r = -0.27, P = 0.02). Patients with leptin concentrations ≥20,676 pg/mL experienced greater increases in cSLEDAI-2K scores over the past year compared to those with lower levels (P = 0.03). Multivariate regression analysis indicated that neither BMI nor leptin levels demonstrated statistically significant associations with cSLEDAI-2K scores, though positive correlational trends were observed. The study findings suggest that approximately one-third of SLE patients were overweight or obese, with this subgroup showing higher prevalence of metabolic comorbidities including cardiovascular risk factors.
Obesity affects 29%–50% of SLE patients and may accelerate disease pathogenesis. Adipose tissue acts as an endocrine organ, releasing adipokines, complement components, and pro-inflammatory mediators, and increases estrogen production via aromatase, a factor linked to SLE risk through early menarche, oral contraceptive use, and menopausal hormone therapy. Obesity can impair treatment response, hasten disease progression, worsen prognosis, and increase cardiovascular and renal complications. It also negatively impacts quality of life, underscoring the importance of addressing nutritional status to optimize treatment and outcomes. A study by Kamel et al. found that serum leptin and adiponectin levels were significantly higher in SLE patients compared to healthy controls and were positively correlated with disease activity (SLEDAI scores). Elevated leptin was associated with lupus nephritis, higher BMI, ESR, CRP, total cholesterol, and uric acid, while elevated adiponectin was also linked to lupus nephritis. These findings suggest that both adipokines are involved in SLE pathogenesis and may serve as potential diagnostic biomarkers and therapeutic targets.
The research highlighted the potential role of leptin as a metabolic marker in SLE, given its strong correlation with BMI and association with specific disease manifestations. While the mechanistic relationship between leptin, obesity, and SLE disease activity requires further investigation, the study emphasized the clinical importance of maintaining optimal weight management in SLE patients to potentially reduce cardiovascular disease risk, lower leptin levels, and improve overall disease outcomes. Future investigations should focus on leptin-targeted therapeutic strategies and examine leptin’s prognostic value in SLE-related cardiovascular complications.
References
- Aeamsaard N, Chaiamnuay S, Narongroeknawin P, Asavatanabodee P, Pakchotanon R. The association between serum leptin levels, body mass index, and disease activity in women with systemic lupus erythematosus. Medicine (Baltimore). 2025 Aug 1;104(31):e43646.
- Carvalho LM, Carvalho BG, Souza LL, da Mota JC, Ribeiro AA, Nicoletti CF. Obesity as an aggravating factor of systemic lupus erythematosus disease: What we already know and what we must explore. A rapid scoping review. Nutrition. 2024 Dec;128:112559.
- Cozier YC, Barbhaiya M, Castro-Webb N, Conte C, Tedeschi S, Leatherwood C, Costenbader KH, Rosenberg L. A prospective study of obesity and risk of systemic lupus erythematosus (SLE) among Black women. Semin Arthritis Rheum. 2019 Jun;48(6):1030-1034.
- Kamel SM, Abdel Azeem Abd Elazeem MEMI, Mohamed RA, Kamel MM, Abdel Aleem Abdelaleem EA. High serum leptin and adiponectin levels as biomarkers of disease progression in Egyptian patients with active systemic lupus erythematosus. Int J Immunopathol Pharmacol. 2023 Jan-Dec;37:3946320231154988.