Maternal Interleukin-6: Marker of Fetal Growth and Adiposity

Radaelli, Tatjana; Uvena-Celebrezze, Jennifer; Minium, Judi; Huston-Presley, Larraine; Catalano, Patrick M.; Mouzon, Sylvie Hauguel-de

doi:10.1016/j.jsgi.2005.10.003

Cited by 88 publications

(67 citation statements)

References 32 publications

(7 reference statements)

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“…We have examined the inflammatory status exacerbates the basal inflammatory state of pregnancy. Increased insulin resistance and higher leptin concentrations reflecting the increase in fat mass of obese women were associated with higher circulating concentrations of CRP and IL-6 supporting findings from our group and others that obesity in pregnancy worsens the pre-gravid inflammatory state [30,31]. In contrast, plasma TNF-alpha concentrations remained unchanged suggesting that production from placental cells and PBMC does not contribute significantly to the circulating concentration similar to TNF-alpha from white adipose tissue [32].…”

Section: Discussionsupporting

confidence: 76%

Obesity in Pregnancy Stimulates Macrophage Accumulation and Inflammation in the Placenta

et al. 2008

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Obesity and pregnancy are associated with a combination of insulin resistance and inflammatory changes which exacerbate in combination. Based on the similarity between the inflammatory transcriptomes of adipose tissue and placenta, we hypothesized that the placenta develops exaggerated inflammation in response to obesity. The aim of this study was to characterize placental inflammatory mediators and macrophage accumulation in relation to peripheral inflammation in obesity.Placental macrophages and maternal peripheral mononuclear cells from 20 obese and 15 lean women were functionally and phenotypically characterized using immunohistochemistry, flow cytometry and expression for macrophage markers and inflammatory cytokines. The number of resident CD68+ and CD14+ cells was increased 2-3 fold in placenta of obese as compared to lean women. The enhanced macrophage population was characterized by a marked phenotypic heterogeneity with complex subsets of CD14+, CD68+ and CD11b+ cells and by an increased expression of the pro-inflammatory mediators IL-1, TNF-alpha, IL-6. Placental inflammation was associated with an activation of peripheral blood mononuclear cells with high amount of CD14, TNF-alpha, IL-6 and the chemokine receptors CCR2 and IL8-R in maternal but not fetal circulation. Additionally, plasma CRP and IL-6 concentrations were higher in obese compared to lean women.In conclusion, the chronic inflammation state of pre-gravid obesity is extending to in utero life with accumulation of an heterogeneous macrophage population and proinflammatory mediators in the placenta. The resulting inflammatory milieu in which the fetus develops may have critical consequences for short and long term programming of obesity. KeywordsObesity; pregnancy; placenta; inflammation; cytokines; fetus; programming The association between excess neonatal adiposity and high pre-gravid BMI and the alarming rise in the number of overweight women of reproductive age, call for elucidating the adverse consequences of obesity in pregnancy (1,2). In non gravid individuals, obesity is described as a low grade inflammatory condition associated with increased production of pro-inflammatory factors which originate from the macrophages infiltrating the adipose tissue (3,4). During pregnancy, however, the placenta becomes a significant source of a variety of cytokines and adipocytokines whose expression is dysregulated by maternal diabetes and obesity (5-7).Pregnancy is considered as a natural inflammatory state evident in activation of maternal leucocytes and increased systemic concentration of acute phase reactants and cytokines (8).The physiological inflammatory state of pregnancy becomes exaggerated when pregnancy is complicated by pre-eclampsia and gestational diabetes and returns to baseline levels after delivery (9-11). Products of inflammatory stress secreted by the placenta and microparticules shedding from the syncytial surface of the placenta into the systemic circulation have been proposed as mechanisms driving adaptive immunity (1...

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Section: Discussionsupporting

confidence: 76%

Obesity in Pregnancy Stimulates Macrophage Accumulation and Inflammation in the Placenta

et al. 2008

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“…CRP and ICAM-1 are increased in adults with obesity (34 -38) and type 2 diabetes (39,40), and similar relationships also appear to be present in childhood (19). At birth, OT1DM have increased fat mass and an associated increased circulating leptin concentration (41,42). It is thus of considerable interest that CRP and ICAM-1 are not only increased in OT1DM but also associated with cord leptin and skinfold thickness.…”

Section: Discussionmentioning

confidence: 92%

Inflammation and Endothelial Activation Is Evident at Birth in Offspring of Mothers With Type 1 Diabetes

et al. 2007

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OBJECTIVE-Offspring of mothers with diabetes are at risk of obesity and glucose intolerance in later life. In adults, markers of subclinical inflammation (C-reactive protein [CRP] and interleukin [IL]-6) and endothelial activation (intracellular adhesion molecule [ICAM]-1) are associated with obesity and higher risk for incident type 2 diabetes. We examined whether these biomarkers were elevated at birth in offspring of type 1 diabetic mothers (OT1DM).RESEARCH DESIGN AND METHODS-Umbilical cord plasma CRP, IL-6, and ICAM-1 were measured in 139 OT1DM and 48 control offspring, with analysis relative to fetal lipids and hormonal axes.RESULTS-OT1DM had higher median (interquartile range) CRP (OT1DM 0.17 mg/l [0.13-0.22] vs. control subjects 0.14 mg/l [0.12-0.17], P Ͻ 0.001) and ICAM-1 (OT1DM 180 ng/ml vs. control subjects 166 ng/ml , P ϭ 0.047). IL-6 was not different after necessary adjustment for mode of delivery. Birth weight was unrelated to inflammatory indexes; however, leptin was correlated with CRP (control subjects r ϭ 0.33, P ϭ 0.02; OT1DM r ϭ 0.41, P Ͻ 0.001) and with IL-6 (r ϭ 0.23, P Ͻ 0.01) and ICAM-1 (r ϭ 0.29, P Ͻ 0.001) in OT1DM. In OT1DM, CRP correlated with maternal glycemic control (A1C at 35-40 weeks; r ϭ 0.28, P ϭ 0.01). In multivariate analysis, leptin was a determinant of CRP (P Ͻ 0.001), ICAM-1 (P ϭ 0.003), and IL-6 (P ϭ 0.02) in OT1DM. Inflammatory measures demonstrated positive relationships with triglycerides in OT1DM (CRP, IL-6, and ICAM-1 P Ͻ 0.05) and control subjects (ICAM-1 P ϭ 0.001).CONCLUSIONS-Inflammatory markers are increased in OT1DM and are related to measures of fetal adiposity, particularly leptin, and maternal glycemia. Subclinical inflammation is a novel component of the diabetic intrauterine environment and should be considered a potential etiological mechanism for in utero programming of disease. Diabetes 56:2697-2704, 2007 M aternal diabetes is associated with adverse consequences to mother and baby. Rates of macrosomia and fetal adiposity are higher, resulting in substantive increases in intrapartum complications, independent of increased background risk of perinatal morbidity and mortality. In the longer term, offspring have increased risk of obesity and type 2 diabetes (1,2) in high-risk populations, reflecting potential in utero programming of disease. In adults, inflammatory markers-in particular C-reactive protein (CRP), intracellular adhesion molecule (ICAM)-1, and interleukin (IL)-6 -are associated with adiposity, altered glucose tolerance, and, prospectively, with later risk of development of type 2 diabetes and vascular disease (3-8). In animal models, intrauterine exposure to cytokines, including IL-6, have been associated with increases in fat mass and insulin resistance in later life (9). Changes in inflammatory markers have not been extensively studied in offspring of type 1 diabetic pregnancies at birth; however, gestational diabetes mellitus has been associated with an alteration in the placental transcriptome with a dominance of genes regulating inflam...

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“…One potential mechanism for the lack of regulation of fat oxidation in vivo may be increased production of adipocytokines [45]. 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].…”

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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Maternal Interleukin-6: Marker of Fetal Growth and Adiposity

Cited by 88 publications

References 32 publications

Obesity in Pregnancy Stimulates Macrophage Accumulation and Inflammation in the Placenta

Obesity in Pregnancy Stimulates Macrophage Accumulation and Inflammation in the Placenta

Inflammation and Endothelial Activation Is Evident at Birth in Offspring of Mothers With Type 1 Diabetes

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

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