title: Increased placental expression of fibroblast growth factor 21 in gestational diabetes mellitus.
abstract: BACKGROUND
  Fibroblast growth factor 21 (FGF21) can regulate glucose and lipid metabolism. The placenta actively synthesizes and secretes many hormones, but it is unknown whether this includes FGF21. This study aimed to analyze the placental expression of FGF21 in women with or without gestational diabetes mellitus (GDM).
  
  
  METHODS
  FGF21 and peroxisome proliferator-activated receptor (PPAR)-α mRNA and protein expression were measured in the placentae of 20 women with and 18 without GDM. mRNA expression of PPARα, FGF receptors 1-4, the coreceptor β-klotho, and glucose transporter (GLUT)-1, -3, and -4 was investigated. Maternal and fetal circulating FGF21 levels were assessed in 10 mother-baby dyads per condition.
  
  
  RESULTS
  FGF21 was expressed in the placenta and its mRNA expression increased in women with GDM [10.75 (interquartile range 3.28-125.6 AU)] vs control [0.83 (0.22-4.78), P < .001], as is its protein expression [GDM 2.89 (1.44-5.10)] vs control [0.42 (0.05-1.98), P < .05]. PPARα mRNA but not protein expression was increased in GDM [2.94 (0.70-7.26)] vs control [0.99 (0.43-2.17), P < .05] and was positively correlated to FGF21 mRNA expression (ρ = 0.43, P < .01). Placental mRNA expression of FGF receptors and GLUT1 was unchanged, and β-klotho, GLUT3, and GLUT4 showed increased expression in GDM. Maternal circulating FGF21 levels were similar [GDM 323 (75-921) vs control 269 (49-731) pg/mL, P = .81]. FGF21 was undetected in fetal cord blood.
  
  
  CONCLUSIONS
  FGF21 is expressed in the placenta and its expression is increased in GDM. The absence of FGF21 in fetal cord blood suggests that neither placental FGF21 nor maternal circulating FGF21 is secreted into the fetal circulation. Placental FGF21 may be a regulator of placental metabolism.
authors.affiliation: School of Medicine (M.D.N., H.L.B., D.M., L.K.C.), University of Queensland Centre for Clinical Research (M.D.N., H.L.B., M.H.K., K.S.R.), School of Biomedical Sciences (K.J.D., T.M.W.), The University of Queensland, Brisbane 4029, Australia; and Mater Health Services (H.D.M.), Brisbane 4101, Australia.
authors.forename: Marloes
authors.initials: M
authors.lastname: Dekker Nitert
authors.forename: Helen L
authors.initials: HL
authors.lastname: Barrett
authors.forename: Marta H
authors.initials: MH
authors.lastname: Kubala
authors.forename: Katherin
authors.initials: K
authors.lastname: Scholz Romero
authors.forename: Kerina J
authors.initials: KJ
authors.lastname: Denny
authors.forename: Trent M
authors.initials: TM
authors.lastname: Woodruff
authors.forename: H David
authors.initials: HD
authors.lastname: McIntyre
authors.forename: Leonie K
authors.initials: LK
authors.lastname: Callaway
mesh_terms: D000328:Adult; D001774:Blood Chemical Analysis; D016022:Case-Control Studies; D016640:Diabetes, Gestational / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005312:Fetal Blood / Q000737:chemistry / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D010920:Placenta / Q000737:chemistry / Q000378:metabolism*; D011247:Pregnancy; D015854:Up-Regulation / Q000235:genetics
chemical_list: C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors