title: Maternal obesity modulates intracellular lipid turnover in the human term placenta.
abstract: Obesity before pregnancy is associated with impaired metabolic status of the mother and the offspring later in life. These adverse effects have been attributed to epigenetic changes in utero, but little is known about the role of placental metabolism and its contribution to fetal development.
  
  
  
  We examined the impact of maternal pre-pregnancy obesity on the expression of genes involved in placental lipid metabolism in lean and obese women.
  
  
  
  Seventy-three lean and obese women with healthy pregnancy were recruited at term elective cesarean delivery. Metabolic parameters were measured on maternal venous blood samples. Expression of 88 genes involved in lipid metabolism was measured in whole placenta tissue. Proteins of genes differently expressed in response to maternal obesity were quantified, correlated with maternal parameters and immunolocalized in placenta sections. Isolated primary trophoblasts were used for in vitro assays.
  
  
  
  Triglyceride (TG) content was increased in placental tissue of obese (1.10, CI 1.04-1.24 mg g-1, P<0.05) vs lean (0.84, CI 0.72-1.02 mg g-1) women. Among target genes examined, six showed positive correlation (P<0.05) with maternal pre-pregnancy BMI, namely ATGL (PNPLA2), FATP1 (SLC27A1), FATP3 (SLC27A3), PLIN2, PPARG and CGI-58 (ABHD5). CGI-58 protein abundance was twofold higher (P<0.001) in placentas of obese vs lean women. CGI-58 protein levels correlated positively with maternal insulin levels and pre-pregnancy body mass index (R=0.63, P<0.001 and R=0.64, P<0.001, respectively). CGI-58 and PLIN2 were primarily located in the syncytiotrophoblast and, were upregulated (1.38- and 500-fold, respectively) upon oleic acid and insulin treatment of cultured trophoblast cells.
  
  
  
  Pre-gravid obesity significantly modifies the expression of placental genes related to transport and storage of neutral lipids. We propose that the upregulation of CGI-58, a master regulator of TG hydrolysis, contributes to the turnover of intracellular lipids in placenta of obese women, and is tightly regulated by metabolic factors of the mother.
authors: Department of Obstetrics and Gynecology, Medical Univeristy of Graz, Auenbruggerplatz 14, Graz, Austria.
authors: B
authors: B
authors: Hirschmugl
authors: Department of Obstetrics and Gynecology, Medical Univeristy of Graz, Auenbruggerplatz 14, Graz, Austria.
authors: G
authors: G
authors: Desoye
authors: Department of Reproductive Biology, MetroHealth Medical Center, Case Western Reserve University Cleveland, Cleveland, OH, USA.
authors: P
authors: P
authors: Catalano
authors: Core Facility Molecular Biology, Center for Medical Research, Medical University of Graz, Graz, Austria.
authors: I
authors: I
authors: Klymiuk
authors: Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Auenbruggerplatz 15, Graz, Austria.
authors: H
authors: H
authors: Scharnagl
authors: Department of Obstetrics and Gynecology, Medical Univeristy of Graz, Auenbruggerplatz 14, Graz, Austria.
authors: S
authors: S
authors: Payr
authors: Department of Obstetrics and Gynecology, Medical Univeristy of Graz, Auenbruggerplatz 14, Graz, Austria.
authors: E
authors: E
authors: Kitzinger
authors: Department of Obstetrics and Gynecology, Medical Univeristy of Graz, Auenbruggerplatz 14, Graz, Austria.
authors: C
authors: C
authors: Schliefsteiner
authors: Department of Obstetrics and Gynecology, Medical Univeristy of Graz, Auenbruggerplatz 14, Graz, Austria.
authors: U
authors: U
authors: Lang
authors: Department of Obstetrics and Gynecology, Medical Univeristy of Graz, Auenbruggerplatz 14, Graz, Austria.
authors: C
authors: C
authors: Wadsack
authors: Department of Reproductive Biology, MetroHealth Medical Center, Case Western Reserve University Cleveland, Cleveland, OH, USA.
authors: S
authors: S
authors: Hauguel-de Mouzon
mesh_terms: D000328:Adult; D002585:Cesarean Section; D005260:Female; D047109:Fetal Development; D006801:Humans; D007231:Infant, Newborn; D007333:Insulin Resistance; D050356:Lipid Metabolism / Q000502:physiology*; D050155:Lipogenesis / Q000502:physiology*; D008431:Maternal-Fetal Exchange; D009765:Obesity / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000378:metabolism* / Q000503:physiopathology; D047929:Term Birth; D013851:Thinness / Q000378:metabolism*