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.
Highlights
Leptin, a 16 kDa non-glycosylated polypeptide product of the obese gene [1], is an adipocyte-derived hormone that participates in the regulation of energy homeostasis [2], neuroendocrine function [3], angiogenesis [4,5], bone formation [6] and reproduction [7]
In a relatively large sample of healthy newborns born to healthy mothers, we found no significant correlation between cord blood leptin levels and anthropometric characteristics of the mothers
Leptin levels correlated with birth weight and length; the correlations were relatively stronger for males than females, in accordance to [41]
Summary
A 16 kDa non-glycosylated polypeptide product of the obese (ob) gene [1], is an adipocyte-derived hormone that participates in the regulation of energy homeostasis [2], neuroendocrine function [3], angiogenesis [4,5], bone formation [6] and reproduction [7]. Leptin is mainly expressed in the adipose tissue, and in the placenta, bone marrow, stomach, brain, muscle and fetal tissues [12,13]. Leptin regulates fetal growth, placental angiogenesis and mobilization of maternal fat [13]. The human placenta expresses high amounts of leptin mRNA and protein in early, mid, and late gestation [14,15]. Adipocytes have not been found in placental tissue [16]
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