hsa‑miR‑155‑5p concentration as a determinant of leptinemia in umbilical cord plasma

Childhood obesity, which is reaching alarming prevalence worldwide, is associated with long‑term adverse metabolic and cardiovascular health outcomes and often persists into adulthood. Investigating the mechanisms responsible for weight gain in early life is essential to better understand and prevent obesity and its related comorbidities. Leptin is a hormone primarily secreted by adipocytes. It suppresses appetite and increases energy expenditure through neonatal programming of the hypothalamic neural circuits responsible for regulation of food intake. The mechanisms regulating leptinemia are not fully understood. MicroRNAs (miRNAs), short RNA molecules repressing protein synthesis of their target genes and secreted in bloodstream, may play a role. To identify circulating miRNAs whose levels are associated with leptinemia in umbilical cord plasma (UCP), the present study quantified the miRNAs from 273 newborns in the Gen3G prospective birth cohort using next‑generation sequencing (NGS). A total of 73 miRNAs were associated with leptinemia (P≤0.05) in UCP. Of these, miR‑183‑5p and miR‑155‑5p were selected to be requantified by digital PCR for 201 of these newborns based on the strength of their association [Log₂(fold‑change)=0.22, P=0.0007 and Log2(fold‑change)=‑0.14, P=0.005, respectively]. Association with leptinemia was replicated for miR‑155‑5p (Pearson correlations: NGS, r=‑0.13, P=0.03; dPCR, r=‑0.12, P=0.04). Biological pathways analysis showed that miR‑155‑5p is predicted to target the leptin receptor mRNA. These findings suggest miR‑155‑5p may influence leptinemia in UCP and contribute to early‑life adiposity programming.