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Sample Preparation to Bioinformatics Analysis of DNA Methylation: Association Strategy for Obesity and Related Trait Studies
Published on: May 6, 2022
Leptin-specific epigenetic modulation of preterm cord blood serves as a candidate biomarker for obesity
Navya Sree Boga1, Amit K Banerjee1, Saikanth Varma1
1National Institute of Nutrition, Indian Council of Medical Research, Hyderabad, India.
Insights
Epigenetic changes in the LEP gene and increased IL6 expression in preterm neonates may promote inflammation and increase later obesity risk. This study identifies early biomarkers for predicting obesity in preterm infants.
Area of Science:
- Endocrinology
- Epigenetics
- Neonatal Research
Background:
- Leptin regulates body weight and adiposity.
- Preterm neonates experience rapid growth, potentially increasing future obesity risk.
- The epigenetic role of leptin in preterm infant obesity risk is not well understood.
Purpose of the Study:
- To investigate the epigenetic regulation of the leptin (LEP) gene in preterm neonates.
- To explore the association between LEP methylation, leptin levels, and inflammatory markers.
- To identify potential early biomarkers for obesity risk in preterm infants.
Main Methods:
- Measured global and LEP promoter methylation in cord blood.
- Assessed levels of leptin and IGF1.
- Quantified the expression of LEP, LEPR, IL6, and TNFα genes in cord blood from preterm and term neonates.
Main Results:
- Preterm neonates showed decreased global and LEP methylation with increased leptin, LEP, LEPR, IL6, and TNFα expression.
- Cord blood leptin levels positively correlated with birth weight in preterm infants.
- LEP methylation was inversely associated with IGF1, while IL6 expression correlated with leptin and LEP expression in preterm cord blood.
Conclusions:
- Epigenetic dysregulation of the LEP gene and elevated IL6/TNFα expression contribute to a pro-inflammatory state in preterm neonates.
- The interplay between LEP methylation and IL6 may promote inflammation, increasing obesity risk.
- This study highlights potential early-life biomarkers for predicting obesity and metabolic disorders in preterm infants.
Background:
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.
Method:
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.
Results:
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.
Conclusion:
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.
Impact:
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.
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