title: Maternal obesity programs mitochondrial and lipid metabolism gene expression in infant umbilical vein endothelial cells.
abstract: Maternal obesity increases risk for childhood obesity, but molecular mechanisms are not well understood. We hypothesized that primary umbilical vein endothelial cells (HUVEC) from infants of overweight and obese mothers would harbor transcriptional patterns reflecting offspring obesity risk.
  
  
  
  In this observational cohort study, we recruited 13 lean (pre-pregnancy body mass index (BMI) <25.0 kg m-2) and 24 overweight-obese ('ov-ob', BMI⩾25.0 kg m-2) women. We isolated primary HUVEC, and analyzed both gene expression (Primeview, Affymetrix) and cord blood levels of hormones and adipokines.
  
  
  
  A total of 142 transcripts were differentially expressed in HUVEC from infants of overweight-obese mothers (false discovery rate, FDR<0.05). Pathway analysis revealed that genes involved in mitochondrial and lipid metabolism were negatively correlated with maternal BMI (FDR<0.05). To test whether these transcriptomic patterns were associated with distinct nutrient exposures in the setting of maternal obesity, we analyzed the cord blood lipidome and noted significant increases in the levels of total free fatty acids (lean: 95.5±37.1 μg ml-1, ov-ob: 124.1±46.0 μg ml-1, P=0.049), palmitate (lean: 34.5±12.7 μg ml-1, ov-ob: 46.3±18.4 μg ml-1, P=0.03) and stearate (lean: 20.8±8.2 μg ml-1, ov-ob: 29.7±17.2 μg ml-1, P=0.04), in infants of overweight-obese mothers.
  
  
  
  Prenatal exposure to maternal obesity alters HUVEC expression of genes involved in mitochondrial and lipid metabolism, potentially reflecting developmentally programmed differences in oxidative and lipid metabolism.
authors.affiliation: Universidade Federal de Pernambuco, Recife, Pernambuco, Brazil.|Research Division, Joslin Diabetes Center, Boston, MA, USA.|Harvard Medical School, Boston, MA, USA.
authors.forename: S M R
authors.initials: SM
authors.lastname: Costa
authors.affiliation: Research Division, Joslin Diabetes Center, Boston, MA, USA.|Harvard Medical School, Boston, MA, USA.
authors.forename: E
authors.initials: E
authors.lastname: Isganaitis
authors.affiliation: Research Division, Joslin Diabetes Center, Boston, MA, USA.
authors.forename: T J
authors.initials: TJ
authors.lastname: Matthews
authors.affiliation: Research Division, Joslin Diabetes Center, Boston, MA, USA.
authors.forename: K
authors.initials: K
authors.lastname: Hughes
authors.affiliation: Research Division, Joslin Diabetes Center, Boston, MA, USA.
authors.forename: G
authors.initials: G
authors.lastname: Daher
authors.affiliation: Research Division, Joslin Diabetes Center, Boston, MA, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Dreyfuss
authors.affiliation: Universidade Federal de Pernambuco, Recife, Pernambuco, Brazil.
authors.forename: G A P
authors.initials: GA
authors.lastname: da Silva
authors.affiliation: Research Division, Joslin Diabetes Center, Boston, MA, USA.|Harvard Medical School, Boston, MA, USA.
authors.forename: M-E
authors.initials: ME
authors.lastname: Patti
mesh_terms: D000328:Adult; D015331:Cohort Studies; D005260:Female; D047109:Fetal Development; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism*; D006801:Humans; D007223:Infant; D007249:Inflammation / Q000503:physiopathology; D050356:Lipid Metabolism / Q000235:genetics*; D039382:Maternal Nutritional Physiological Phenomena / Q000502:physiology; D008928:Mitochondria / Q000378:metabolism; D009035:Mothers; D009765:Obesity / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D011247:Pregnancy; D011248:Pregnancy Complications / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011297:Prenatal Exposure Delayed Effects; D014470:Umbilical Cord / Q000166:cytology*