title: GDM-Induced Macrosomia Is Reversed by Cav-1 via AMPK-Mediated Fatty Acid Transport and GLUT1-Mediated Glucose Transport in Placenta.
abstract: OBJECTIVE
  To investigate if the role of Cav-1 in GDM-induced macrosomia is through regulating AMPK signaling pathway in placenta.
  
  
  METHODS
  We used diagnostic criteria of gestational diabetes mellitus (GDM) and macrosomia to separate and compare placental protein and mRNA levels from GDM with macrosomia group (GDMM), GDM with normal birth weight group (GDMN) and normal glucose tolerance (NGT) with normal birth weight group (CON). Western blotting was performed to examine differentially expressed proteins of caveolin-1 (Cav-1) and Adenosine monophosphate-activated protein kinase (AMPK) signaling pathway related proteins, including phosphorylated-AMPKα(Thr172), AMPKα, phosphorylated-Acetyl-CoA carboxylase(Ser79) (p-ACC(Ser79)), ACC and glucose transporter 1 (GLUT1) in placenta between the three groups. The mRNA levels of Cav-1, AMPKα, ACC and GLUT1 in placenta were measured by real time-PCR.
  
  
  RESULTS
  In the GDMM placenta group, both protein and mRNA levels of Cav-1 were down-regulated, while GLUT1 was up-regulated; the phosphorylation and mRNA levels of ACC and AMPKα were decreased, but total ACC protein levels were increased compared to both the GDMN (p<0.05) and CON groups (p<0.05). In GDMM placenta group, there was a significant negative correlation observed between neonatal birth weight (NBW) and protein expression levels of Cav-1, p-ACC(Ser79) and p-AMPKα(Thr172) (p<0.05), while positive relationship with ACC and GLUT1 protein levels. Besides, in GDMM group placental mRNA levels, NBW had a positive correlation with GLUT1 (p<0.05), while negative with Cav-1, AMPKα and ACC expression (p<0.05). Cav-1 protein expression was positively associated with p-AMPK and p-ACC (p<0.05), and negatively associated with GLUT1 (p<0.05). Interestingly, p-AMPK protein expression was closely related to p-ACC (p<0.05), but not with GLUT1.
  
  
  CONCLUSIONS
  GDM-induced macrosomias have more severe inhibition of Cav-1 expression in placenta. Cav-1 is associated with placental glucose and fatty acid transport via the induction of AMPK signaling pathway and the reduction of GLUT1 signaling pathway to reverse GDM-induced macrosomia.
authors.affiliation: Department of Pediatrics, Qilu Hospital of Shandong University, Jinan, China.|Department of Pediatrics, Taian City Central Hospital, Taian, China.
authors.forename: Guo
authors.initials: G
authors.lastname: Yao
authors.affiliation: Department of Pediatrics, Taian City Central Hospital, Taian, China.|Department of Pathophysiology, Taishan Medical University, Taian, China.
authors.forename: Yafang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Taian City Central Hospital, Taian, China.
authors.forename: Di
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Pathophysiology, Taishan Medical University, Taian, China.
authors.forename: Ruirui
authors.initials: R
authors.lastname: Yang
authors.affiliation: Department of Pathophysiology, Taishan Medical University, Taian, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Sang
authors.affiliation: Department of Pathophysiology, Taishan Medical University, Taian, China.
authors.forename: Linlin
authors.initials: L
authors.lastname: Han
authors.affiliation: Department of Pathophysiology, Taishan Medical University, Taian, China.
authors.forename: Yuexia
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Taian City Central Hospital, Taian, China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Taian City Central Hospital, Taian, China.
authors.forename: Yeke
authors.initials: Y
authors.lastname: Tan
authors.affiliation: Department of Pathophysiology, Taishan Medical University, Taian, China.
authors.forename: Zhanping
authors.initials: Z
authors.lastname: Shang
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D000328:Adult; D001692:Biological Transport; D001724:Birth Weight / Q000502:physiology; D051242:Caveolin 1 / Q000378:metabolism*; D016640:Diabetes, Gestational / Q000378:metabolism*; D050612:Fatty Acid Transport Proteins / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D005320:Fetal Macrosomia / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1 / Q000378:metabolism*; D006801:Humans; D010766:Phosphorylation; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D015398:Signal Transduction / Q000502:physiology; D055815:Young Adult
chemical_list: C495540:CAV1 protein, human; D051242:Caveolin 1; D050612:Fatty Acid Transport Proteins; D005227:Fatty Acids; D051272:Glucose Transporter Type 1; D055372:AMP-Activated Protein Kinases; C000588423:ACACA protein, human; D000103:Acetyl-CoA Carboxylase; D005947:Glucose