Leptin-specific epigenetic modulation of preterm cord blood serves as a candidate biomarker for obesity.

Abstract

Leptin communicates the body's energy utilisation and maintains a stable body weight. Preterm neonates often show rapid compensatory catch-up growth, which may increase the risk of obesity later in life. Although leptin regulates adiposity, its epigenetic role in the obesity risk of preterm neonates remains unclear. Global and LEP promoter methylation, leptin and IGF1 levels, and expression of LEP and IL6 genes were measured in umbilical cord blood from preterm and term deliveries. Genome-wide and LEP-specific methylation were decreased, while circulatory leptin, LEP, LEPR, IL6, and TNFα expression were increased in preterm cord blood (p < 0.05). Cord blood leptin levels were positively associated with birth weight in preterm (r = 0.288, p = 0.03). LEP methylation was inversely associated (r = -0.506, p = 0.03) with IGF1, while IL6 expression positively correlated with leptin (r = 0.318, p = 0.05), and LEP expression (r = 0.278, p = 0.03) in preterm cord blood. The interplay between LEP methylation and IL6 can influence each other in promoting inflammation, which may increase the risk of obesity in preterm neonates in later life. While leptin's role in adiposity is established, its epigenetic influence on the obesity risk of preterm neonates is unknown. Epigenetic dysregulation of the LEP gene, together with increased expression of IL6 and TNFα, led to a pro-inflammatory state in preterm neonates. This is the first study to report LEP-specific promoter methylation and its association with pro-inflammatory markers, exploring early-life biomarkers for predicting obesity. Predicting early biomarkers of obesity might have implications for the early identification and management of metabolic disorders in preterm neonates. Maternal factors leading to preterm birth and cord blood leptin dysregulation in predicting obesity. Elevated blood pressure, infection, and lower haemoglobin in preterm disrupted epigenetic control of leptin and activated inflammation. Leptin dysregulation may affect satiety and body fat, thereby increasing the risk of obesity. Solid arrows depict present data, and dotted lines indicate potential pathways.