Free-to-Total Leptin Ratio in Maternal Plasma is Constant Throughout Human Pregnancy

Abstract

Abstract. To clarify the mechanism of leptin resistance during pregnancy, we measured plasma leptin concentrations, free to total leptin ratio (percent free leptin) and soluble leptin receptor concentrations in pregnant women, and compared the results with those in non-pregnant women. We collected plasma samples from 23 non-pregnant and 31 pregnant women in the third trimester. Plasma samples from 5 pregnant women were collected longitudinally in each trimester. Plasma leptin concentrations in pregnant women in the second trimester (17.4 ± 3.2 ng/ml) were higher than those in the first trimester of pregnancy (11.0 ± 2.8 ng/ml, n = 5), as previously reported. However, percent free leptin did not change significantly throughout pregnancy. Percent free leptin correlated with total leptin concentrations (ng/ml) in non-pregnant women (r = 0.727, P<0.0001), but not in women in the third trimester of pregnancy (r = 0.006). Constant percent free leptin during pregnancy despite increased leptin concentrations indicates increased leptin binding capacity in pregnant women, that might partly contribute to the establishment of leptin resistance. On the other hand, soluble leptin receptor concentrations showed significant negative correlation with BMI and plasma leptin concentrations in pregnant women (r = -0.470, P<0.01 and r = -0.493, P<0.01, respectively) but not in non-pregnant women. These data suggest the possibility that soluble leptin receptor is a minor component of leptin binding capacity in the plasma of pregnant women.

The Relationship between Maternal Plasma Leptin Levels and Fetal Growth Restriction

“…The magnitude of free leptin fraction was similar to that of protein binding fraction in normal pregnant women (Fig. 3A), which was compatible with our previous observation [17]. In contrast, the former is dominant in preeclamptic women and non-preeclamptic women with SGA neonates (Fig.…”

“…However, leptin binding protein was yet to be clarified precisely, and its physiological function is not well known. We previously demonstrated that in normal pregnant women, free-to-total leptin ratio in maternal plasma is constant throughout pregnancy [17] and during labor [12]. In the present study, protein binding leptin was eluted in one peak in GPC analysis using Sephadex G-50.…”

“…We have demonstrated a rather constant percent free leptin ratio during pregnancy, despite elevated maternal leptin concentrations, indicating that leptin binding capacity is increased in pregnant women [17]. The physiological and pathophysiological implications of increased leptin and its binding proteins during pregnancy have yet to be fully elucidated.…”

“…Circulating leptin is bound to some leptin binding proteins [12,17], thus it form two different peaks, when eluted in gel filtration analysis, i.e., bound leptin and free leptin. We have demonstrated a rather constant percent free leptin ratio during pregnancy, despite elevated maternal leptin concentrations, indicating that leptin binding capacity is increased in pregnant women [17].…”

Effect of reducing the n‐6/n‐3 fatty acid ratio on the maternal and fetal leptin axis in relation to infant body composition

“…While increasing leptin concentrations during pregnancy are welldocumented (8,9), data on changes in sOB-R over the course of pregnancy and lactation are less consistent (19)(20)(21). We observed an increase in maternal sOB-R concentration during pregnancy, followed by a significant decrease after delivery and a further decrease during the lactation period.…”