LEPTIN RECEPTOR GENE EXPRESSION AND ITS ASSOCIATION WITH CARDIOVASCULAR RISK MARKERS IN OBESE SUBJECTS: A CASE–CONTROL STUDY FROM SOUTH INDIA
TL;DR
LEPR gene expression is significantly upregulated in obesity and is positively associated with circulating leptin concentrations, suggesting altered leptin signaling in obese individuals and may serve as a promising molecular biomarker for identifying obesity-associated cardiometabolic risk.
Abstract
Background: Obesity is a major global health concern associated with chronic inflammation, metabolic dysregulation, and an increased risk of cardiovascular disease (CVD). Altered leptin receptor (LEPR) signalling has been implicated in obesity-related cardiometabolic complications; however, evidence regarding LEPR gene expression and its relationship with cardiovascular risk markers in the South Indian population remains limited. Objective: To evaluate LEPR gene expression and investigate its association with biochemical, inflammatory, and cardiovascular risk markers among obese adults. Methods: A hospital-based case–control study was conducted involving 300 adults, including 150 obese subjects and 150 apparently healthy controls. Anthropometric measurements, fasting biochemical parameters, lipid profile, thyroid profile, renal function tests, inflammatory biomarkers (hs-CRP, TNF-α, IL-6), cardiac biomarkers (NT-proBNP, ST2, and PAPP A), serum leptin concentrations, and LEPR gene expression were assessed. Relative LEPR expression was quantified using quantitative real-time polymerase chain reaction. Group comparisons were performed using the Mann–Whitney U test, while correlations between LEPR expression and clinical variables were analysed using Spearman's rank correlation. Results: Obese participants demonstrated significantly higher body mass index, fasting blood glucose, triglycerides, total cholesterol, LDL cholesterol, hs-CRP, TNF-α, IL-6, NT-proBNP, ST2, PAPP-A, serum leptin concentrations, and LEPR gene expression than controls (all p < 0.001). LEPR gene expression was significantly elevated in obese subjects (1.45 ± 0.83 vs. 1.02 ± 0.17-fold change; p < 0.001). Within the obese group, LEPR expression showed a significant positive correlation with serum leptin (r = 0.345, p < 0.001) and serum creatinine (r = 0.192, p = 0.018), whereas no significant associations were observed with body mass index, lipid profile, inflammatory markers, or cardiac biomarkers. Conclusion: LEPR gene expression is significantly upregulated in obesity and is positively associated with circulating leptin concentrations, suggesting altered leptin signaling in obese individuals. LEPR expression may serve as a promising molecular biomarker for identifying obesity-associated cardiometabolic risk. Further multicentre longitudinal studies are warranted to validate its prognostic value and clinical applicability.