Adiponectin Expression in Human Fetal Tissues during Mid- and Late Gestation (original) (raw)
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Adiponectin in maternal and fetal cord blood during pregnancy and its relation to fetal birth weight
IP innovative publication pvt. ltd, 2019
Abstract Introduction: Adiponectin has been implicated in the physiology of insulin resistance during pregnancy. Insulin resistance is developed in the last half of pregnancy. Insulin has a direct influence on fetal growth and proven in past studies. Hence we can state that the adiponectin also has a effect on fetal development and growth and since it is a key regulator in the insulin sensitivity. The aim of the present study is to increase the knowledge of role of adiponectin, especially in a physiologically demanding state of pregnancy, and study its effect on development of a fetus by virtue of its birth weight and gestational age during a normal pregnancy. Materials and Methods: This open-ended non-comparative prospective study was conducted at the outpatient and inpatient department of Obstetrics and Gynecology as well as in the department of Biochemistry, Sawai Man Singh Medical College, Jaipur on 50 normal pregnant subjects and their neonates attending Obstetrics and Gynecology, department for routine checkups during the period of August 2014 to July 2015. Levels of adiponectin in maternal serum during mid-trimester and pre-labor stage of pregnancy were evaluated and compared. The evaluation of maternal and fetal adiponectin levels were also done in relation to birth weight and gender. Results: Adiponectin is detectable in pregnant subjects, with significantly higher levels seen in newborns; however, there was no relationship seen between maternal and fetal adiponectin levels at any stage of gestation (Midterm p=0.604, Full-term p=0.589). Mean Birth weight of newborns was noted at 2.95 (± 0.445) kg with slightly lower values in male babies. Statistically significant positive correlation was seen between fetal birth weights and fetal adiponectin levels (p<0.01). Conclusion: Adiponectin is a plausible candidate for illuminating some physiologic and pathophysiologic conditions associated with pregnancy and fetal growth. Our study concludes with the hope of further breakthrough studies in the clinical application of this very interesting molecule in the management of various metabolic diseases of newborns and adults. Keywords: Infant, Growth, Ponderal index, Insulin resistance.
Diabetologia, 2006
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.
Problem statement: Similar to obese patients and type 2 diabetic patients, adiponectin levels are reduced in former Gestational Diabetes Mellitus (GDM) patients and are lower in GDM women during late pregnancy compared with pregnant control subjects matched for BMI. Diabetic insult at later stages in gestation, such as may occur in gestational diabetes, will foremost lead to shortterm changes in a variety of molecules for key functions including gene expression in the placenta. Approach: In this study we assessed the expression of adiponectin receptors in human placenta to identify the site (s) of expression and to clarify the effect of gestational diabetes in this expression. This study was carried on 10 normoglycemic pregnant women and 20 GDM women. The placental tissue was collected immediately after delivery and tissue biopsies were taken from both fetal and maternal sides of each placenta. One step-RT-PCR for ADIPOR1 and ADIPOR2 was done by Real Time PCR using Syber Green technique. Relative quantification of mRNA of the ADIPOR1 and ADIPOR2 genes was measured using ABI7900 Real Time machine. Results: Both types of Adiponectin Receptors (ADIPOR1 and ADIPOR2) are expressed in human placenta. ADIPOR1 is more highly expressed than ADIPOR2 in both fetal and maternal sides of GDM cases and normal pregnant women. ADIPOR1 mRNA expression was significantly up regulated in GDM women compared to normal pregnant women, whereas no significant difference in the expression of ADIPOR2 was detected between the two groups. There was no evidence of maternal-fetal side difference in the expression of adiponectin receptors in GDM cases but in normal pregnant women there is a statistically significant difference between both sides in the expression of both ADIPOR1 and ADIPOR2. Conclusion: We concluded that adiponectin plays an important role in mediation the glucose metabolism in fetal tissues through its receptors, mainly Adiponectin Receptor 1 (ADIPOR1).
The Journal of Clinical Endocrinology & Metabolism, 2008
Context: High plasma adiponectin concentrations in human fetuses and neonates are unique features of early developmental stages. Yet, the origins of the high adiponectin concentrations in the perinatal period remain elusive. Objective: This study was undertaken to identify the sources and functional properties of adiponectin in utero. Design and Methods: Tissue specimens were obtained at autopsy from 21-to 39-wk-old stillborn human fetuses. Adipose tissue and placenta were obtained at term elective cesarean section. Adiponectin complexes and expression were measured by immunodetection and real-time PCR. Results: Adiponectin mRNA transcripts were detected in fetal sc and omental adipose depots at lower concentrations than in maternal adipose tissue. Immunoreactive adiponectin was also observed in vascular endothelial cells of fetal organs, including skeletal muscle, kidney, and brain. The absence of adiponectin in all placental cell types and lack of correlation between maternal and umbilical adiponectin indicate that umbilical adiponectin reflects its exclusive production by fetal tissues. The most prominent forms of adiponectin in fetal plasma were high and low molecular mass (HMW and LMW) multimers of 340 and 160 kDa, respectively. The proportion of the HMW complexes was 5-fold (P Ͻ 0.001) higher in umbilical plasma than in adult. The high HMW and total adiponectin levels were associated with lower insulin concentration and lower homeostasis model of assessment of insulin resistance indices in umbilical plasma, reflecting higher insulin sensitivity of the fetus compared with adult. Conclusions: The abundance of HMW adiponectin and its vascular expression are characteristics of human fetal adiponectin. Combined with high insulin sensitivity, fetal adiponectin may be a critical determinant of in utero growth.
Patterns of Adiponectin expression in term pregnancy; impact of obesity
The Journal of Clinical Endocrinology & Metabolism, 2014
Context: Adiponectin (adpN) production is down-regulated in several situations associated with insulin resistance. The hypoadiponectinemia which develops in late pregnancy suggests a role of adpN in pregnancy-induced insulin resistance.
Adiponectin in human cord blood: relation to fetal birth weight and gender
American Journal of Obstetrics and Gynecology, 2003
Adiponectin is an adipocyte-derived plasma protein with insulin-sensitizing and antiatherosclerotic properties. The aim of this study was to examine whether adiponectin is present in human fetal blood, to define its association with fetal birth weight, and to evaluate whether dynamic changes in adiponectin levels occur during the early neonatal period. Cord blood adiponectin levels were extremely high (71.0 ؎ 21.0 g/ml; n ؍ 51) compared with serum levels in children and adults and positively correlated with fetal birth weights (r ؍ 0.4; P < 0.01). No significant differences in adiponectin levels were found between female and male neonates. In addition, there was no correlation between cord adiponectin levels and maternal body mass index, cord leptin, or insulin levels. Cord adiponectin levels were significantly higher compared with maternal levels at birth (61.1 ؎ 19.0 vs. 17.6 ؎ 4.9 g/ml; P < 0.001; n ؍ 17), and no correlation was found between cord and maternal adiponectin levels. There were no significant differences between adiponectin levels at birth and 4 d postpartum (61.1 ؎ 19.0 vs. 63.8 ؎ 22.0 g/ml; n ؍ 17). These findings indicate that adiponectin in cord blood is derived from fetal and not from placental or maternal tissues. The high adiponectin levels in newborns compared with adults may be due to lack of negative feedback on adiponectin production resulting from lack of adipocyte hypertrophy, low percentage of body fat, or a different distribution of fat depots in the newborns.
Adiponectin in Pregnancy: Implications for Health and Disease
Current Medicinal Chemistry, 2012
Pregnancy is a unique physiologic state that is associated with profound alterations in maternal metabolic, endocrine, and vascular function, designed to ensure the delivery of appropriate energy and nutrition to the developing fetus. In this context, the role of the fat-derived hormone adiponectin is of interest, particularly in light of emerging recognition of the broad array of physiologic processes upon which this adipokine impacts. Indeed, adiponectin has pleiotropic effects on the regulation of energy homeostasis, systemic inflammation, vascular function, cell growth, and even bone metabolism. Thus, in this review, we consider existing evidence for the physiologic role of adiponectin in human gestation and how this protein may be relevant to two major medical disorders of pregnancy: gestational diabetes mellitus and preeclampsia. While studies to date have yielded many conflicting findings pertaining to adiponectin in pregnancy, further investigation in this area is essential. Ultimately, elucidation of adiponectin physiology in the setting of both normal pregnancy and its pathologic conditions may provide unique insight into fundamental processes that are relevant to health and disease in mother and child.
Adiponectin multimers in maternal plasma
Journal of Maternal-fetal & Neonatal Medicine, 2008
Objective-Adiponectin is an anti-diabetic, anti-atherogenic, anti-inflammatory and angiogenic adipokine that circulates in oligomeric complexes including: low-molecular-weight (LMW) trimers, medium-molecular-weight (MMW) hexamers and high-molecular-weight (HMW) isoforms. The aim of this study was to determine whether there are changes in adiponectin multimers in pregnancy and as a function of maternal weight.
Current Medicinal Chemistry
Pregnancy is a unique physiologic state that is associated with profound alterations in maternal metabolic, endocrine, and vascular function, designed to ensure the delivery of appropriate energy and nutrition to the developing fetus. In this context, the role of the fat-derived hormone adiponectin is of interest, particularly in light of emerging recognition of the broad array of physiologic processes upon which this adipokine impacts. Indeed, adiponectin has pleiotropic effects on the regulation of energy homeostasis, systemic inflammation, vascular function, cell growth, and even bone metabolism. Thus, in this review, we consider existing evidence for the physiologic role of adiponectin in human gestation and how this protein may be relevant to two major medical disorders of pregnancy: gestational diabetes mellitus and preeclampsia. While studies to date have yielded many conflicting findings pertaining to adiponectin in pregnancy, further investigation in this area is essential....
Expression and Regulation of Adiponectin and Receptor in Human and Rat Placenta
The Journal of Clinical Endocrinology & Metabolism, 2005
Context: Adiponectin is an adipocyte hormone involved in glucose and lipid metabolism. Recently, two receptors of this protein, called adiponectin receptor 1 (Adipo-R1) and Adipo-R2, have been cloned. Objective: The aim of this study was to examine whether adiponectin and its receptors are expressed in human and rat placentas and to evaluate the regulation of these factors by gestational age and nutritional status.