Leptin modulates nitric oxide production and lipid metabolism in human placenta

Abstract

Leptin has significant effects on appetite, energy expenditure, lipid mobilisation and reproduction. During pregnancy, leptin is produced in the placenta, a tissue in which leptin receptors are highly expressed, suggesting autocrine/paracrine functions for this hormone. In the present study, a putative role of leptin as a regulator of nitric oxide (NO) production and lipid metabolism was evaluated in term human placenta. We demonstrated that leptin enhanced NO production in human placental explants (P < 0.01). Although leptin did not modify the placental levels of cholesteryl esters and phospholipids, leptin decreased levels of triglycerides (P < 0.01) and cholesterol (P < 0.001) in term human placenta. The effect of leptin on lipid mass seems to be independent of the modulation of de novo lipid synthesis because leptin did not modify the incorporation of (14)C-acetate into any of the lipids evaluated. We investigated the effects of leptin on placental lipid catabolism and found that in both term human placental explants and primary cultures of trophoblastic cells, leptin increased glycerol release, an index of the hydrolysis of esterified lipids, in a dose-dependent manner. In conclusion, we have shown that leptin affects NO production and lipid catabolism in human placenta, providing supportive evidence for a role of leptin in placental functions that would determine the transfer of nutrients to the developing fetus.

Saturated fat-rich diet increases fetal lipids and modulates LPL and leptin receptor expression in rat placentas

“…In previous work, we showed a leptin dose-dependent increase in placental lipolysis in the human placenta (White et al 2006). Leptin administration to term gestation fetuses showed an increase in Lpl expression in the placenta, suggesting that fetal leptin modulates the transport of lipids to the fetus.…”

“…Lipases are important in placental lipid transfer to the fetus (White et al 2006). We investigated whether a saturated fat-rich diet is able to modify placental and fetal liver Lpl and El expression.…”

“…Leptin induces lypolysis and fatty acid oxidation in adipocytes, muscle, and placenta (Muoio et al 1997, Fruhbeck & Gomez-Ambrosi 2001, White et al 2006. Also, leptin enhances placental amino acid transport to the fetus (Jansson et al 2003, von Versen-Hoynck et al 2009).…”

Peroxisome proliferator-activated receptor α activation regulates lipid metabolism in the feto-placental unit from diabetic rats

“…FFAs were determined by employing a colorimetric commercial kit (Randox Laboratories, Antrim, UK). Glycerol was determined by an enzymatic method as described previously (Young et al 1988, White et al 2006. Briefly, 0.2 ml placental explant incubation medium was allowed to react with 1 ml assay solution containing glycine (15 mg/ml), MgCl 2 (0.4 mg/ml), ATP (0.75 mg/ml), NAD C (0.36 mg/ml), hydrazine hydrate (0.2 ml/ ml), glycerokinase (0.42 units/ml) and glycerol-3-phosphate dehydrogenase (2.5 units/ml; Roche Diagnostics Corporation).…”

Arsenic-Associated Oxidative Stress, Inflammation, and Immune Disruption in Human Placenta and Cord Blood

“…Leptin is tightly regulated and involved in key processes in fetal development, including transfer of nutrients from placenta to the developing fetus (Jansson et al 2003;White et al 2006). Placental leptin production is increased during hypoxia (Spranger et al 2008) and in various obstetrical conditions such as diabetes, preeclampsia, and intrauterine growth retardation (Iwagaki et al 2004;Mise et al 1998).…”