TNF-α Is a Predictor of Insulin Resistance in Human Pregnancy

Kirwan, John P.; Mouzon, Sylvie Hauguel-de; Lepercq, J.; Challier, Jean-Claude; Huston-Presley, Larraine; Friedman, Jacob E.; Kalhan, Satish C.; Catalano, Patrick M.

doi:10.2337/diabetes.51.7.2207

Cited by 643 publications

(551 citation statements)

References 46 publications

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“…Furthermore, recent studies found that the rise in TNF-a and leptin levels during pregnancy are correlated with the decline in insulin sensitivity. 5 These data are in accordance with levels of leptin reported in the present study. Adiponectin is a novel adipocytokine produced abundantly and exclusively in adipose tissue.…”

Section: Commentsupporting

confidence: 93%

“…4 Lately, studies have implicated that adipocytokines, such as tumor necrosis factor alpha (TNF)-a) and leptin, are probable regulators of insulin resistance in pregnancy. 5 Adiponectin is an adipocytokine produced abundantly and exclusively in adipose tissue. A large body of evidence from experimental and epidemiological studies in adults has supported the important role of adiponectin in regulating insulin resistance and glucose homeostasis.…”

Section: Introductionmentioning

confidence: 99%

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Maternal serum adiponectin levels during human pregnancy

et al. 2007

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Objective: Pregnancy is a unique situation characterized by insulin resistance. The role of adiponectin, an insulin-sensitizing hormone, has not been completely clarified during pregnancy. The aim of this cross-sectional study was to evaluate adiponectin levels during pregnancy and postpartum. Study design:Adiponectin and leptin levels were tested in 80 pregnant women, 20 in each trimester (mean gestational age 10.5±1.9; 19.3±4.9; 39.3±0.8 weeks,) as well as 4 days postpartum.Results: Adiponectin levels during first (13.3±3.6 mg/ml), second (12.6±4.4 mg/ml) and third trimester (11.2±3.7 mg/ml) did not differ and were significantly higher than postpartum levels (8.8±2.1 mg/ml; P<0.0001, P<0.004 and P<0.02, respectively). Conclusion:Despite increased insulin resistance during pregnancy, no significant alterations in adiponectin levels were observed. This may imply that the regulation of adiponectin during gestation is altered. The elevated gestational adiponectin levels are consistent with increased 'adiponectin resistance' during pregnancy.

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Section: Commentsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Maternal serum adiponectin levels during human pregnancy

et al. 2007

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“…During pregnancy, this could also be contributed to by the low-grade inflammatory situation originating in white adipose tissue and placenta through increased production of various cytokines including IL-6 and TNF-α [46,47]. In addition, TNF-α is the best predictor of peripheral insulin resistance during pregnancy and, at the same time, is able to reduce adiponectin expression and secretion [45,48]. Taking all of this into account, we view the pregnancy-mediated increase in TNF-α as an important functional link between hypoadiponectinaemia and insulin resistance.…”

Section: Functional Significance Of Hypoadiponectinaemiamentioning

confidence: 99%

Adiponectin in human pregnancy: implications for regulation of glucose and lipid metabolism

et al. 2006

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Aims/hypothesis: Adiponectin is upregulated during adipogenesis and downregulated in insulin-resistant states. The mechanism(s) governing the re-arrangements from adipogenesis to facilitated lipolysis during pregnancy are unknown. Our purpose was to analyse the role of adiponectin relative to the metabolic changes in human pregnancy. Subjects, materials and methods: Lean women (BMI <25 kg/m²) were evaluated longitudinally before conception, and in early (12-14 weeks) and late (34-36 weeks) pregnancy. Insulin sensitivity was measured using the glucose clamp technique. Venous blood and subcutaneous adipose tissue biopsies were obtained at each time point. Results: Adiponectin concentrations were lower in the third trimester than in the pregravid condition (9.9±1.4 vs 13.5±1.8 μg/ml). The hypoadiponectinaemia was reflected by a 2.5-fold decrease in white adipose tissue adiponectin mRNA. These changes were associated with a 25% increase in fat mass (23.7±2.9 vs 18.9±2.9 kg). Insulin infusion decreased high molecular weight adiponectin complexes in pregravid women (9.9±0.6 vs 6.2±0.06) and the suppressive effect of insulin was lost during pregnancy. The pregnancy-mediated changes in adiponectin were strongly correlated with basal insulin levels and insulin sensitivity (p<0.0001). The relationship between adiponectin and insulin sensitivity was related to the decreased insulin regulation of glucose utilisation (r=0.55, p<0.001) but not of endogenous hepatic glucose production. Conclusions/interpretation: These data demonstrate that pregnancy is associated with adiponectin changes in lean women. Hypoadiponectinaemia is reflected by a lower amount of high molecular weight adiponectin and by the ratio of high to low molecular weight multimers. The adiponectin changes relate to decreased insulin sensitivity of glucose disposal rather than alterations of lipid metabolism.

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“…Gestational diabetes mellitus (GDM), a state of increased insulin resistance, can lead to complications during pregnancy and may also increase the risk of stillbirth [8].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2006

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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.

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TNF-α Is a Predictor of Insulin Resistance in Human Pregnancy

Cited by 643 publications

References 46 publications

Maternal serum adiponectin levels during human pregnancy

Maternal serum adiponectin levels during human pregnancy

Adiponectin in human pregnancy: implications for regulation of glucose and lipid metabolism

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

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