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-(TNF-), 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-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.

Regulation of adiponectin release and demonstration of adiponectin mRNA as well as release by the non-fat cells of human omental adipose tissue

“…28 Approximately, the same rate of release was seen by cut pieces of adipose tissue that did not contain enough lipid to float. 28 The view that the expression of adiponectin mRNA is restricted to mature adipocytes is clearly untenable in view of the present findings and the recent reports that adiponectin is synthesized and secreted by human osteoblasts, 10 human cardiomyocytes, 11 murine skeletal muscle, 12 human skeletal muscle and placenta, 13 human liver biopsies, 14 human placental synctiotrophoblasts, 15 as well as human fetal tissues of both mesodermal and ectodermal origin. 16 The present data using omental adipose tissue explants confirm the prior reports by Matsuzawa's laboratory that adiponectin release is reduced by obesity 4 as well as diabetes.…”

“…7,8 Adiponectin was originally described as an adipocytespecific protein. [1][2][3] However, more recently adiponectin mRNA and secretion have been demonstrated in boneforming cells, 9,10 cardiomyocytes, 11 skeletal muscle, 12,13 human liver, 14 human placental syncytiotrophoblasts 15 and human fetal tissues of mesodermic and ectodermal origin. 16 It is unclear whether tissues other than adipose tissue contribute to circulating levels of adiponectin that are some 40-fold higher than those of leptin in obese subjects.…”

The ‘beneficial’ adipokines in reproduction and fertility

“…Studies have further shown that the trophoblast and placenta are local sources of adiponectin expression. 55,56 In vitro tissue explant studies of human term placenta indicate that adiponectin can be secreted 57 and that it upregulates placental cytokine release. 58 Together, these studies strongly suggest paracrine effects of adiponectin in placental function.…”

“…10 In human aortic endothelial cells, the cyclic AMP or protein kinase A pathway was evoked by adiponectin, 68,69 whereas in other endothelial cell models, the phosphoinositol kinase 3/protein kinase B (PKB) or Akt system transduces the adiponectin signal. 34 There is evidence for adiponectin activation of the peripheral peroxisome-activated receptor-g in placental tissue 57 and mitogen-activated protein kinase pathways in vascular tissue 70,71 and osteoblasts. 72 The recent discovery of interactions between the AdipoR1 and R2 and the adapter protein APPL1 28,29 has provided new insight into the mechanism by which adiponectin can act on target tissues.…”

Maternal serum adiponectin levels during human pregnancy

“…Another possible explanation for the reduced postpartum levels of adiponectin may be cessation of transport from the placenta. Although several investigators found placental expression of adiponectin, 26,27 others failed to find the placenta as a novel site for adiponectin expression. 28 Given the controversy in the literature, we cannot rule out this possibility.…”