Zinc-α2-glycoprotein is unrelated to gestational diabetes: anthropometric and metabolic determinants in pregnant women and their offspring.

CONTEXT: Zinc-α2-Glycoprotein (ZAG) is an adipokine with lipolytic action and is positively associated with adiponectin in adipose tissue. We hypothesize that ZAG may be related with hydrocarbonate metabolism disturbances observed in gestational diabetes mellitus (GDM). OBJECTIVE: The aim of this study was to analyze serum ZAG concentration and its relationship with carbohydrate metabolism in pregnant women and its influence on fetal growth. DESIGN: 207 pregnant women (130 with normal glucose tolerance (NGT) and 77 with GDM) recruited in the early third trimester and their offspring were studied. Cord blood was obtained at delivery and neonatal anthropometry was assessed in the first 48 hours. ZAG was determined in maternal serum and cord blood. RESULTS: ZAG concentration was lower in cord blood than in maternal serum, but similar concentration was observed in NGT and GDM pregnant women. Also similar levels were found between offspring of NGT and GDM women. In the bivariate analysis, maternal ZAG (mZAG) was positively correlated with adiponectin and HDL cholesterol, and negatively correlated with insulin and triglyceride concentrations, and HOMA index. On the other hand, cord blood ZAG (cbZAG) was positively correlated with fat-free mass, birth weight and gestational age at delivery. After adjusting for confounding variables, gestational age at delivery and HDL cholesterol emerged as the sole determinants of cord blood ZAG and maternal ZAG concentrations, respectively. CONCLUSION: mZAG was not associated with glucose metabolism during pregnancy. ZAG concentration was lower in cord blood compared with maternal serum. cbZAG was independently correlated with gestational age at delivery, suggesting a role during the accelerated fetal growth during latter pregnancy

Serum activin A and follistatin levels in gestational diabetes and the association of the Activin A-Follistatin system with anthropometric parameters in offspring.

CONTEXT: The Activin A-Follistatin system has emerged as an important regulator of lipid and glucose metabolism with possible repercussions on fetal growth. OBJECTIVE: To analyze circulating activin A, follistatin and follistatin-like-3 (FSTL3) levels and their relationship with glucose metabolism in pregnant women and their influence on fetal growth and neonatal adiposity. DESIGN AND METHODS: A prospective cohort was studied comprising 207 pregnant women, 129 with normal glucose tolerance (NGT) and 78 with gestational diabetes mellitus (GDM) and their offspring. Activin A, follistatin and FSTL3 levels were measured in maternal serum collected in the early third trimester of pregnancy. Serial fetal ultrasounds were performed during the third trimester to evaluate fetal growth. Neonatal anthropometry was measured to assess neonatal adiposity. RESULTS: Serum follistatin levels were significantly lower in GDM than in NGT pregnant women (8.21±2.32 ng/mL vs 9.22±3.41, P = 0.012) whereas serum FSTL3 and activin A levels were comparable between the two groups. Serum follistatin concentrations were negatively correlated with HOMA-IR and positively with ultrasound growth parameters such as fractional thigh volume estimation in the middle of the third trimester and percent fat mass at birth. Also, in the stepwise multiple linear regression analysis serum follistatin levels were negatively associated with HOMA-IR (β = -0.199, P = 0.008) and the diagnosis of gestational diabetes (β = -0.138, P = 0.049). Likewise, fractional thigh volume estimation in the middle of third trimester and percent fat mass at birth were positively determined by serum follistatin levels (β = 0.214, P = 0.005 and β = 0.231, P = 0.002, respectively). CONCLUSIONS: Circulating follistatin levels are reduced in GDM compared with NGT pregnant women and they are positively associated with fetal growth and neonatal adiposity. These data suggest a role of the Activin-Follistatin system in maternal and fetal metabolism during pregnancy

Munc18c in adipose tissue is downregulated in obesity and is associated with insulin.

Journal Article;OBJECTIVE Munc18c is associated with glucose metabolism and could play a relevant role in obesity. However, little is known about the regulation of Munc18c expression. We analyzed Munc18c gene expression in human visceral (VAT) and subcutaneous (SAT) adipose tissue and its relationship with obesity and insulin. MATERIALS AND METHODS We evaluated 70 subjects distributed in 12 non-obese lean subjects, 23 overweight subjects, 12 obese subjects and 23 nondiabetic morbidly obese patients (11 with low insulin resistance and 12 with high insulin resistance). RESULTS The lean, overweight and obese persons had a greater Munc18c gene expression in adipose tissue than the morbidly obese patients (p<0.001). VAT Munc18c gene expression was predicted by the body mass index (B = -0.001, p = 0.009). In SAT, no associations were found by different multiple regression analysis models. SAT Munc18c gene expression was the main determinant of the improvement in the HOMA-IR index 15 days after bariatric surgery (B = -2148.4, p = 0.038). SAT explant cultures showed that insulin produced a significant down-regulation of Munc18c gene expression (p = 0.048). This decrease was also obtained when explants were incubated with liver X receptor alpha (LXRα) agonist, either without (p = 0.038) or with insulin (p = 0.050). However, Munc18c gene expression was not affected when explants were incubated with insulin plus a sterol regulatory element-binding protein-1c (SREBP-1c) inhibitor (p = 0.504). CONCLUSIONS Munc18c gene expression in human adipose tissue is down-regulated in morbid obesity. Insulin may have an effect on the Munc18c expression, probably through LXRα and SREBP-1c.This work was supported in part by grants from Instituto de Salud Carlos III [CP04/00133, PS09/01060, PS09/00997], Servicio Andaluz de Salud [PI0255/2007]. L. Garrido-Sánchez is supported by a fellowship from the Programa Juan de la Cierva [JCI-2009-04086]. E. Garcia-Fuentes is supported by the Research Stabilization Program of the Instituto de Salud Carlos III (ISCIII). R. El Bekay is supported by fellowships from the Fondo de Investigación Sanitaria (FIS) "Miguel Servet" [CP07/00288].Ye

Munc18c in adipose tissue is downregulated in obesity and is associated with insulin.

Journal Article;OBJECTIVE Munc18c is associated with glucose metabolism and could play a relevant role in obesity. However, little is known about the regulation of Munc18c expression. We analyzed Munc18c gene expression in human visceral (VAT) and subcutaneous (SAT) adipose tissue and its relationship with obesity and insulin. MATERIALS AND METHODS We evaluated 70 subjects distributed in 12 non-obese lean subjects, 23 overweight subjects, 12 obese subjects and 23 nondiabetic morbidly obese patients (11 with low insulin resistance and 12 with high insulin resistance). RESULTS The lean, overweight and obese persons had a greater Munc18c gene expression in adipose tissue than the morbidly obese patients (p<0.001). VAT Munc18c gene expression was predicted by the body mass index (B = -0.001, p = 0.009). In SAT, no associations were found by different multiple regression analysis models. SAT Munc18c gene expression was the main determinant of the improvement in the HOMA-IR index 15 days after bariatric surgery (B = -2148.4, p = 0.038). SAT explant cultures showed that insulin produced a significant down-regulation of Munc18c gene expression (p = 0.048). This decrease was also obtained when explants were incubated with liver X receptor alpha (LXRα) agonist, either without (p = 0.038) or with insulin (p = 0.050). However, Munc18c gene expression was not affected when explants were incubated with insulin plus a sterol regulatory element-binding protein-1c (SREBP-1c) inhibitor (p = 0.504). CONCLUSIONS Munc18c gene expression in human adipose tissue is down-regulated in morbid obesity. Insulin may have an effect on the Munc18c expression, probably through LXRα and SREBP-1c.This work was supported in part by grants from Instituto de Salud Carlos III [CP04/00133, PS09/01060, PS09/00997], Servicio Andaluz de Salud [PI0255/2007]. L. Garrido-Sánchez is supported by a fellowship from the Programa Juan de la Cierva [JCI-2009-04086]. E. Garcia-Fuentes is supported by the Research Stabilization Program of the Instituto de Salud Carlos III (ISCIII). R. El Bekay is supported by fellowships from the Fondo de Investigación Sanitaria (FIS) "Miguel Servet" [CP07/00288].Ye

Clinical and metabolic characteristics of the population studied.

<p>Value data are presented as mean ± SD or median (25–75th percentile) for nonnormally distributed.</p><p>variables. mAdiponectin: maternal adiponectin, cbAdiponectin: cord blood adiponectin, SBP: systolic.</p><p>blood pressure, DBP: diastolic blood pressure.</p

Correlation between serum cbZAG levels and anthropometric variables: birth weight (A) and fat-free mass (FFM) (B).

<p>Correlation between serum cbZAG levels and anthropometric variables: birth weight (A) and fat-free mass (FFM) (B).</p

Correlation between serum mZAG levels and HDL cholesterol levels (A), triglyceride levels (B), Insulin logarithm (Lg Insulin) (C) and HOMA-IR logarithm (Lg HOMA-IR) (D).

<p>Correlation between serum mZAG levels and HDL cholesterol levels (A), triglyceride levels (B), Insulin logarithm (Lg Insulin) (C) and HOMA-IR logarithm (Lg HOMA-IR) (D).</p

Stepwise multiple linear regression models of activin A, follistatin and FSTL3.

<p>* Model 1: Covariates considered for selection: maternal age, diagnosis of GDM, LogHOMA-IR, LogPre-pregnancy BMI, BMI gain, and triglycerides.</p><p>**Model 2: Covariates considered for selection: The same as in model 1, follistatin and FSTL3.</p><p><i>r²</i>: corrected R².</p

Serum follistatin levels in the NGT group compared with the GDM group.

<p>Serum follistatin levels in the NGT group compared with the GDM group.</p

Clinical, metabolic and ultrasound characteristics of the population studied.

<p>Value data are presented as mean ± SD or median (25^th–75^th percentile) for non-normally distributed variables. SBP: systolic blood pressure, DBP: diastolic blood pressure, FWE: fetal weight estimation, FTVE: fractional thigh volume estimation SDS: standard deviation score.</p