Secretion of adiponectin by human placenta: differential modulation of adiponectin and its receptors by cytokines

Abstract

Aims/hypothesis: Pregnancy, a state of insulin resistance, is associated with elevated levels of cytokines and profound alterations in metabolism. Serum adiponectin, an adipokine with anti-inflammatory and insulinsensitising properties, has been shown to be lower in patients with gestational diabetes mellitus, a state of greater insulin resistance than normal pregnancies. Hypothesising that the human placenta is a source of adiponectin, we investigated its expression and secretion, and the regulation by cytokines of adiponectin and its receptors. Methods: Real-time RT-PCR, radioimmunoassay, Western blotting, radioligand binding and immunofluorescent analyses were applied to demonstrate the expression, secretion and functionality of placental adiponectin. Results: Adiponectin gene expression and protein were found in the human term placenta, with expression primarily in the syncytiotrophoblast. RIA of conditioned media from explant experiments revealed that the placenta can secrete adiponectin in vitro. Addition of conditioned media to HEK-293 cells transfected with the gene for adiponectin receptor-1 (ADIPOR1) altered the phosphorylation status of extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinase, an effect abolished after preabsorption with adiponectin antibody. Cytokines, including TNF-α, IFN-γ, IL-6 and leptin, differentially modulated placental adiponectin receptors as well as adiponectin gene expression and secretion. Interestingly, in placentae from women with gestational diabetes mellitus, we observed significant downregulation of adiponectin mRNA, significant upregulation of ADIPOR1 expression, and a non-significant increase in ADIPOR2 expression.Conclusions/ interpretation: Our results indicate that the human placenta produces and secretes adiponectin, and that adiponectin and its receptors are differentially regulated by cytokines and their expression altered in women with gestational diabetes mellitus. Collectively, our novel data suggest that adiponectin may play a role in adapting energy metabolism at the materno-fetal interface.

CpG Oligodeoxynucleotides Downregulate Placental Adiponectin and Increase Embryo Loss in Non‐Obese Diabetic Mice

“…While the presence of syncytiotrophoblast adiponectin expression has been previously debated,39, 40 the present study demonstrated adiponectin expression in both syncytiotrophoblasts and decidual glands. In the in vitro model cell experiments, we also found that adiponectin was expressed in syncytial BeWo cells.…”

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.…”

Adiponectin gene expression and adipocyte NF-κB transcriptional activity in elderly overweight and obese women: inter-relationships with fat distribution, hs-CRP, leptin and insulin resistance

“…A few in vitro studies have shown either no relation between leptin and adiponectin gene expression or indeed a negative correlation, 27,28 but upregulation of adiponectin gene expression by leptin has been also hypothesized. 6 In our subjects leptin levels were significantly associated with both HOMA and waist circumference whereas the association between leptin and adiponectin gene expression appeared only after adjusting for waist (r ¼ 0.48, P ¼ 0.016).…”