Leptin is a hormone produced from fatty tissue that controls food intake through leptin receptors in the hypothalamic arcuate nucleus. In the regulation between energy intake and consumption, neuropeptide Y (NPY) increases appetite, whereas leptin reduces it by suppressing NPY secretion. Leptin concentrations are related to fatty tissue; leptin levels decrease in lipodystrophic conditions, anorexia, and hunger, and increase in satiation and weight gain (1–3). It has been suggested that leptin triggers precocious activation of hypothalamic-pituitary-gonadal axis in puberty. It has also been shown to trigger onset of puberty in boys (4). It is a metabolic signal protein that informs the hypothalamus that sufficient energy for pubertal development has been stored. Leptin levels gradually increase until birth and decline dramatically after birth in healthy neonates. This may be important for the stimulation of feeding behavior, fetal development, and the acquisition of energy homeostasis in the neonate (5).
Several studies have investigated leptin and NPY levels in children, but the information for newborns in the literature is limited, especially in terms of NPY (5–9). The purpose of this study was to determine leptin and NPY levels in newborns aged from 14 to 28 days.
Materials and methods
This prospective study was intended to determine plasma leptin and plasma NPY levels in neonates admitted to Atatürk University Medical Faculty Research Hospital Neonatal Clinic, Erzurum, Turkey between July and December, 2014 after obtaining signed consent from respective families. Sixty-two newborns aged from 14 to 28 days, 26 female and 36 male, were included in the study. Newborns aged other than 14–28 days or with any disease and premature and postmature newborns were excluded. All newborns were completely healthy. Newborns aged from 14 to 28 days were selected in order to ensure standardization among patients. The hypothalamic-pituitary-gonadal axis performs standard functions at 14–28 days without the period of birth being affected. Once signed consent forms had been received, history of each newborn was taken. Patients’ age, height, and body weight were recorded. Feeding status was also recorded. The newborns were divided into two groups – those receiving breastfeeding only (1st group) and those receiving breastfeeding and formula (2nd group). The newborns in the 2nd group were given both mother’s milk and formula, in no specific proportions. Newborns with any disease or congenital anomaly or with mothers having chronic disease were excluded. The following laboratory protocol was applied to blood specimens collected: 2 mL of blood obtained using routine venous collection was placed into K2EDTA tubes. Specimens were centrifuged and stored at –80°C. Plasma samples were gradually thawed on the day of examination. Plasma leptin levels were measured by the enzyme amplified sensitivity immunoassay (EASIA) method using DIAsource kit (Leptin-EASIA (human) KAP2281, DIAsource ImmunoAssays S.A., Louvain-la-Neuve, Belgium). Plasma NPY levels were measured using the enzyme immunoassay (EIA) method using RayBiotech kit (NPY EIA (human) EIA-NPY-1, RayBiotech, Inc. Georgia, USA). Leptin and NPY levels were expressed as nanograms/milliliter. Ethical approval for the study was granted by the University Ethical Committee (Date 3.7.2014 Session: 7 Decision number: 5).
Patients’ body weight and height were measured. Postnatal ages and body mass indices were calculated. Measurements were expressed as minimum, maximum, and mean and standard deviation. SSPE 20 for Windows software was used for data analysis. The one-sample Kolmogorov-Smirnov test was used to determine whether all numerical data for leptin and NPY in both the sex were normally distributed.
As patients’ NPY values were normally distributed, the independent sample t-test was used. Leptin values were not normally distributed, and the nonparametric two independent samples Mann-Whitney U-test was therefore used. p<0.05 was regarded as significant at statistical analysis.
Sixty-two newborns, 26 female (41.9%) and 36 male (58.1%), were included in the study. Patients’ auxological characteristics and leptin and NPY levels are shown in Table 1. Fifty-two newborns (83.9%) were receiving mother’s milk and 10 newborns (16.1%) mother’s milk and formula. Our patients’ leptin and NPY values were evaluated on the basis of 3rd, 10th, 25th, 50th, 75th, 90th, and 97th percentiles. These are shown in Table 2. No significant difference was observed between both the sex in terms of leptin or NPY levels (leptin p=0.775 and NPY p=0.687). A weak correlation was determined between leptin and NPY (p=0.041, r=0.26). No correlation was determined between leptin and body weight (p=0.50, r=0.087), length (p=0.087, r=–0.21), body mass index (p=0.78, r=0.22), age (p=0.873, r=0.021), or nutritional status (p=0.228, r=–0.123). No correlation was observed between NPY and body weight (p=0.228, r=0.155), length (p=0.24, r=–0.151), body mass index (p=0.51, r=0.249), age (p=0.572, r=0.073), or nutritional status (p=0.144, r=–0.188). These data are shown in Table 3.
Observations show that leptin is not only involved in food intake and energy balance, but also has other metabolic and endocrinological effects (3). It has recently been discovered that leptin can modulate both synapse numbers and synaptic activity in NPY neurons in the hypothalamic arcuate nucleus (10). We detected a weak correlation between leptin and NPY in our study. While there is no doubt that leptin is involved in the onset of puberty, the existing data are insufficient to fully describe the mechanism concerned. Some authors have suggested that a high fat level is needed for the onset of puberty in rats and rodents and that a resulting rise in leptin levels may be a signal for the onset of puberty once that level of fat has been achieved (11).
Leptin levels in our study were higher in females compared to males, although the difference was not statistically significant. Mean leptin levels were 4.25 ng/mL and 3.49 ng/mL in females and males, respectively. Leptin levels being higher in females than males was attributed in one study to greater fat distribution in females (12). Another study suggested that leptin can be attributed to the pubertal increase in circulating estradiol, as clinical data suggest that estrogen increases leptin independent of body fat content in females (13).
Many studies have investigated leptin levels and NPY levels in humans. Leptin levels of –3.49±1.65 ng/mL and NPY levels of 98.5±21.9 μmol/mL have been reported in healthy children (7–17 years). That study also investigated serum leptin and NPY in children with asthma and reported no significant difference according to sex (14). Mean age of the group of children with obesity was 10.81±3.69 years. The leptin level was 36.39±43.25 ng/mL and the NPY level 1.65±2.48 ngl/mL. In the control group, the leptin level was 4.78±2.51 ng/mL and the NPY level 2.95±2.00 ngl/mL (15).
Cord blood sample leptin level in one study was 23.44 ng/mL, compared to 7.82 ng/mL in an adult control group (mean age 26.73 years) (16). Leptin levels were measured in constitutional delayed puberty and in normal puberty. Mean leptin level in constitutional delay of puberty was 13.1±2.0 ng/mL and mean leptin level in normal puberty was 13.0±1.8 ng/mL (mean age 16.1 years). The mean NPY level in constitutional delay of puberty was 199.4±105.1 pg/mL and the mean NPY level in normal puberty was 56.9±26.3 pg/mL (mean age 12.5 years) (17). In another study, leptin and NPY were examined initially and a mean 7.21±2.32 months after treatment in patients with anorexia nervosa. Mean leptin concentration increased from 7.99±2.6 to 9.98±2.48 μg/mL, whereas mean NPY concentration decreased from 34.10±9.81 to 29.6±8.04 pmol/L. These data were statistically significant (18). Leptin levels studied between the 3rd and 90th days of life increased significantly in both male and female newborns. There was no significant difference in the leptin levels and leptin/body mass index ratios in both the sex at different time points (19). We observed no correlation between weight, length, and body mass index and leptin or NPY.
Although several studies have investigated levels of leptin and NPY in children, studies involving newborns are very limited. One study compared serum leptin between twin and singleton infants and reported that serum leptin concentrations in twins (1.13±0.35 ng/mL) were significantly lower than those in the singleton infants (4.27±0.63 ng/mL) (20). In another study investigating the relationship between serum leptin levels and hematological parameters at birth, no correlation was determined between leptin and hemoglobin, leukocyte or platelet count at birth. Leptin levels in that study were 1.63±1.09 (21). In another study of 30 healthy full-term newborns, plasma leptin and plasma NPY levels were compared to umbilical cord blood concentrations. Mean cord blood leptin value was 9.58±4.98 ng/mL and mean cord blood NPY was 44.47±19.35 pmol/L, whereas on the 4th day of life mean leptin was 4.91±6.06 ng/mL and mean NPY was 74.25±29.22 pmol/L. The authors emphasized the significant decrease in plasma leptin concentrations and the increase in plasma NPY concentrations (22). Cord blood leptin levels do not differ in terms of sex or body mass index (23, 24). However, there are studies reporting a relationship between cord blood leptin levels and birth weight (5, 8). In our study, no correlation was determined between weight, length, or body mass index, and serum leptin levels.
Another newborn study examined only leptin levels. The mean plasma leptin concentration in high gestational age infants was 4.83±1.84 ng/mL (range 1.69–8.46), 2.29±0.52 ng/mL (range 1.57–3.30) in average gestational age infants, and 2.23±0.75 ng/mL (range 1.22–3.96) in low gestational age infants. Significant differences were observed in mean leptin concentrations between high and average gestational age infants. However, no significant differences in terms of mean leptin concentrations were observed between low and average gestational age infants (25).
The limitations of this study are the small sample size and that the overall neonatal period was not included.
We determined mean leptin levels of 4.25±3.08 and 3.49±2.52 ng/mL and mean NPY levels of 24.79±9.87 and 25.80±9.58 ng/mL in our 14- to 28-day-old female and male newborns, respectively. In conclusion, leptin and NPY levels in the neonatal period do not differ in terms of sex.
Conflict of interest statement
Funding: No funding
Financial disclosure statement: The authors have no financial disclosures relevant to this article.
Conflict of interest statement: The authors have no conflicts of interest relevant to this article to disclose. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.
Clinical trial registry name and registration number: None
Avni Kaya: Manuscript preparation, patient’s doctor, data acquisition, literature research, approved the final manuscript as submitted.
Zerrin Orbak: Patient’s doctor, manuscript editing, approved the final manuscript as submitted.
İsmail Polat: Patient’s doctor, data acquisition, approved the final manuscript as submitted.
Harun Polat: Biochemical analysis, approved the final manuscript as submitted.
Musa Gümüşdere: Biochemical analysis, approved the final manuscript as submitted.
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About the article
Published Online: 2015-09-03
Published in Print: 2016-01-01