Urocortin Neuropeptide Levels Are Impaired in the PBMCs of Overweight Children

Area of Science:

• Endocrinology
• Neuroscience
• Pediatric Metabolism

Background:

• Corticotropin-releasing hormone (CRH) and urocortins (UCNs) play roles in energy balance and cellular stress.
• Their expression patterns in pediatric populations, particularly concerning obesity, are not well-defined.

Purpose of the Study:

• To investigate the impact of varying body mass index (BMI) on CRH and UCN expression in children.
• To explore the relationship between these neuropeptides and cellular stress markers in vitro.

Main Methods:

• Assessed neuropeptide expression (CRH, UCN1, UCN2, UCN3) in peripheral blood mononuclear cells (PBMCs) and plasma from 40 children (normal weight, overweight, obese).
• Utilized real-time polymerase chain reaction (RT-PCR) to measure gene expression.
• Exposed THP1 cells to high glucose and palmitate to simulate metabolic stress conditions.

Main Results:

• Transcript levels of UCN1, UCN3, and CRH were significantly decreased in PBMCs of overweight and obese children compared to normal-weight children.
• UCN3 mRNA expression showed a strong positive correlation with UCN1, UCN2, and CRH mRNA levels.
• In vitro, palmitate or high glucose/palmitate treatment increased CRH, UCN2, and UCN3 mRNA expression, alongside inflammatory and endoplasmic reticulum stress markers.

Conclusions:

• Reduced expression of CRH and UCNs in PBMCs of obese children suggests their involvement in obesity-related metabolic dysregulation.
• Findings indicate a potential crosstalk between CRH/UCNs and cellular stress pathways, particularly under conditions mimicking metabolic overload.