Cord Blood Leptin Levels of Healthy Neonates Are Associated with IFN-γ Production by Cord Blood T-Cells

Abstract

Leptin is a hormone synthesized by adipocytes and other tissues, including the placenta, and it regulates food intake and energy expenditure, reproductive and immune functions. To investigate the role of leptin in neonatal immunity, we measured serum leptin and cytokine (IFN-γ, TNF-α, IL-2, IL-4, IL-10, IL-12) levels in the cord blood (cb) of 510 healthy neonates, 14 small for gestational age (SGA), 312 appropriately grown for gestational age (AGA) and 184 large for gestational age (LGA). Median serum leptin concentration in the whole sample was 11 ng/ml. In 11.2% neonates (1 SGA, 32 AGA, 24 LGA), leptin levels were >90th percentile (median 39 ng/ml). In 33.3% of those (3.72% of total sample) with the highest leptin levels (median 46 ng/ml), significantly elevated levels of serum IFN-γ were also found (mean 27.11 pg/ml, range 17.5–38.5 pg/ml). In neonates with leptin levels ∼50th percentile (median 12 ng/ml) or <10th percentile (median 1 ng/ml), serum IFN-γ levels were negligible. All other cytokines measured, were < the assays’ detection limits. To investigate whether leptin can independently influence cytokine gene expression by cb T-cells and monocytes (Mc), we cultured cb T-cells or Mc, isolated from randomly selected AGA neonates or adult peripheral blood, with leptin. This resulted in upregulation of IL-2, IFN-γ and IL-4 gene expression in cb and adult T-cells and IL-10 expression mainly in cb-Mc. Significantly higher expression of IFN-γ occurred in female cb-T-cells cultured with leptin, compared with male cb-T-cells. In conclusion, the concurrent presence of high concentrations in both leptin and IFN-γ in cb of healthy infants, and leptin’s ability to directly upregulate cytokine gene expression in cb T and Mc cells, indicate that abnormally high leptin levels can independently influence the immune system of healthy newborns, and may mediate gender differences in the development of a Th1 polarized immune response.

Maternal Body Weight and Gestational Diabetes Differentially Influence Placental and Pregnancy Outcomes

“…Enhanced circulating leptin in obese women was associated with higher leptin and monocyte concentrations in cord blood. In addition to its potential role in newborn adiposity ( 64 , 67 ), growing evidence has linked leptin with the maturation of the hypothalamus ( 68 ) and the fetal and neonatal immune system ( 69 ), leading to impaired immune responses ( 59 ). As part of the PREOBE follow-up, further studies are exploring potential long-term implications of obesity and diabetes in offspring neurodevelopment through functional measurements.…”

Increased serum IgG and IgA in overweight children relate to a less favourable metabolic phenotype

“…In addition, energy restriction decreases serum concentrations of IgG and IgA in overweight women . However, it has also been reported that the appetite‐regulating hormone leptin may modulate different aspects of adaptive immunity .…”

Cord blood klotho levels are inversely associated with leptin in healthy Latino neonates at risk for obesity

“…Although, the weight parameters for our cohort were largely in the normal range with the majority of children having normal birth weight and only 3.2% reporting low birth weight and 8.4% high birth weight, a high percentage had elevated leptin levels. The mean cord blood leptin in our cohort was 23.0 ± 18.4 ng/mL while 25.4% of the cohort had high leptin defined as leptin levels >90th percentile for neonates (>28 ng/mL) from the study by [14]. The mean leptin levels in our cohort were much higher (more than 50%) than the 15.7 ng/mL reported for Taiwanese infants [15] and also higher than the 13.97 ng/mL for large for gestational age infants in a US sample [16].…”