Release and regulation of leptin, resistin and adiponectin from human placenta, fetal membranes, and maternal adipose tissue and skeletal muscle from normal and gestational diabetes mellitus-complicated pregnancies

Abstract

The aim of this study was to determine the release and regulation of leptin, resistin and adiponectin from human placenta and fetal membranes, and maternal subcutaneous adipose tissue and skeletal muscle obtained from normal and gestational diabetes mellitus (GDM)-complicated pregnancies at the time of Cesarean section. Tissue explants were incubated in the absence (basal control) or presence of 10 μg/ml lipopolysaccharide (LPS), 10, 20 or 40 ng/ml tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-8, 1 μM phorbol myristate acetate, 10, 20 and 40 mM glucose, 0.1, 1 and 10 μM insulin and 0.1 1 and 10 μM dexamethasone, progesterone and estrogen. After an 18-h incubation, the medium was collected and the release of leptin, resistin and adiponectin was quantified by ELISA. Human gestational tissues and maternal tissues released immunoreactive leptin, resistin and adiponectin; however, there was no difference in the release of either resistin or adiponectin between normal pregnant women and women with gestational diabetes. The release of leptin was significantly higher in placenta, amnion and choriodecidua obtained from normal pregnant women compared with women with GDM. However, in maternal tissues, the situation was reversed, with adipose tissue and skeletal muscle obtained from women with GDM releasing significantly greater amounts of leptin. In adipose tissue and skeletal muscle the release of leptin was significantly greater in insulin-controlled GDM compared with diet-controlled GDM, and leptin release from adipose tissue was significantly correlated with maternal body mass index. In all tissues tested, there was no effect of incubation with LPS, IL-6, IL-8 or TNF-α on leptin, resistin or adiponectin release. PMA significantly increased the release of resistin from placenta and adipose tissue. Insulin increased placental resistin release, whereas the hormones dexamethasone, progesterone and estrogen significantly decreased placental resistin release. The data presented in this study demonstrate that dysregulation of leptin metabolism and/or function in the placenta may be implicated in the pathogenesis of GDM. Furthermore, resistin release is greatly affected by a variety of inflammatory mediators and hormones.