Leptin alters placental amino acid transport

Maternal leptin is elevated during pregnancy and preeclampsia, and is postulated to be an important mediator of reproductive function and metabolic regulation. Amino acids serve as one of the main nutrient sources for the fetus and the activity of placental amino acid transporters is crucial in the regulation of fetal growth. However, the role of leptin in placental function is not fully understood. Objective: To investigate the role of leptin on system A amino acid transport in human placenta. Methods: The uptake of C14-MeAIB was investigated after incubation of primary villous fragments isolated from placentas of primiparous women with uncomplicated pregnancies in leptin (n=22), insulin (n=14) and angiotensin II (n=14). Western Blotting was performed to identify the leptin receptor and STAT3 phosphorylation as a measure of leptin receptor activation (n=6). Leptin induced matrix metalloproteinase (MMP) activity of villous fragments was measured by zymography (n=5). Data are expressed as mean±SEM of the fold change compared to control. Statistical analyzes was done by Wilcoxon/Kruskal Wallis test, probability values were considered significant at p<0.05. Results: Leptin increased system A amino acid transporter activity by 33% within 1 hr of incubation. However, this increase in activity was lost after 2 hr. Placental villous fragments expressed both the membrane bound leptin receptor and additionally released a soluble leptin receptor. Leptin activated JAK-STAT signaling pathway and increased MMP–9 activity in placental villous fragments. Conclusions: These data support the role of leptin as a signal at the maternal-fetal interface of the human placenta.

Leptin - amino acid transport - placenta - system A