title: Patterns of adiponectin expression in term pregnancy: impact of obesity.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  In obese pregnancy there is a decreased systemic adpN, which results from down-regulation of gene expression in adipose tissue.
  
  
  METHODS
  One hundred and thirty-three women with uncomplicated pregnancies and a wide range in pre-gravid body mass index (18-62 kg/m(2)) were recruited at term for a scheduled cesarean delivery. Maternal blood, placenta, and sc abdominal adipose tissue were obtained in the fasting state. DNA methylation was analyzed by MBD-based genome-wide methylation sequencing and methyl-specific PCR of placenta and maternal adipose tissue. mRNA and protein expression were characterized by real-time RT-PCR and immunodetection. Plasma adpN, leptin, and insulin were assayed by ELISA.
  
  
  RESULTS
  Maternal adipose tissue was the prominent site of adpN gene expression with no detectable mRNA or protein in placenta. In obese women, adipose tissue adpN mRNA was significantly decreased (P < .01) whereas DNA methylation was significantly increased (P < .001) compared with lean women. The decreased adipose tissue expression resulted in normal-weight women having significantly greater plasma adpN compared with the severely obese (12.8 ± 4.3 ng/mL vs 8.6 ± 3.1, P < .001). Plasma adpN was negatively correlated with maternal body mass index (r = -0.28, P < .001) and homeostasis model assessment indices of insulin sensitivity (r = -0.32, P < .001) but not with gestational weight gain.
  
  
  CONCLUSIONS
  Maternal adipose tissue is the primary source of circulating adpN during pregnancy. Further, based on our results, the placenta does not synthesize adiponectin at term. Obesity in pregnancy is associated with negative regulation of adpN adipose expression with increase in adpN DNA methylation associated with lower mRNA concentrations and hypoadiponectinemia. Maternal hypoadiponectinemia may have functional consequences in down-regulating biological signals transmitted by adpN receptors in various tissues, including the placenta.
authors.affiliation: Center of Reproductive Health, Metrohealth Medical Center (M.H., S.B., L.P., D.S., P.M.C., S.H.M.), Case Western Reserve University, Cleveland, Ohio 44106; and Genomic Medicine Institute (D.S.), Cleveland Clinic Lerner Research Institute, Cleveland, Ohio 44195.
authors.forename: Maricela
authors.initials: M
authors.lastname: Haghiac
authors.forename: Subhabrata
authors.initials: S
authors.lastname: Basu
authors.forename: Larraine
authors.initials: L
authors.lastname: Presley
authors.forename: David
authors.initials: D
authors.lastname: Serre
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Catalano
authors.forename: Sylvie
authors.initials: S
authors.lastname: Hauguel-de Mouzon
mesh_terms: D052242:Adiponectin / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism; D000328:Adult; D015992:Body Mass Index; D019175:DNA Methylation / Q000502:physiology*; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D007231:Infant, Newborn; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology; D020738:Leptin / Q000378:metabolism; D009765:Obesity / Q000235:genetics* / Q000378:metabolism; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D011248:Pregnancy Complications / Q000235:genetics* / Q000378:metabolism; D011263:Pregnancy Trimester, Third / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D055815:Young Adult
chemical_list: C499918:ADIPOQ protein, human; D052242:Adiponectin; D007328:Insulin; D020738:Leptin; D012333:RNA, Messenger