title: PPARGC1α gene DNA methylation variations in human placenta mediate the link between maternal hyperglycemia and leptin levels in newborns.
abstract: BACKGROUND
  Children exposed to gestational diabetes mellitus (GDM) are at a higher risk of developing obesity and type 2 diabetes. This susceptibility might involve brown adipose tissue (BAT), which is suspected to protect against obesity. The objective of this study is to assess whether fetal exposure to maternal hyperglycemia is associated with DNA methylation variations in genes involved in BAT genesis and activation.
  
  
  METHODS
  DNA methylation levels at the PRDM16, BMP7, CTBP2, and PPARGC1α gene loci were measured in placenta samples using bisulfite pyrosequencing in E-21 (n = 133; 33 cases of GDM) and the HumanMethylation450 array in Gen3G (n = 172, all from non-diabetic women) birth cohorts. Glucose tolerance was assessed in all women using an oral glucose tolerance test at the second trimester of pregnancy. Participating women were extensively phenotyped throughout pregnancy, and placenta and cord blood samples were collected at birth.
  
  
  RESULTS
  We report that maternal glycemia at the second and third trimester of pregnancy are correlated with variations in DNA methylation levels at PRDM16, BMP7, and PPARGC1α and with cord blood leptin levels. Variations in PRDM16 and PPARGC1α DNA methylation levels were also correlated with cord blood leptin levels. Mediation analyses support that DNA methylation variations at the PPARGC1α gene locus explain 0.8 % of the cord blood leptin levels variance independently of maternal fasting glucose levels (p = 0.05).
  
  
  CONCLUSIONS
  These results suggest that maternal glucose in pregnancy could produce variations in DNA methylation in BAT-related genes and that some of these DNA methylation marks seem to mediate the impact of maternal glycemia on cord blood leptin levels, an adipokine regulating body weight.
authors.affiliation: Department of Biochemistry, Université de Sherbrooke, Sherbrooke, QC Canada.|ECOGENE-21 Laboratory and Lipid Clinic, CIUSSS du Saguenay-Lac-Saint-Jean - Hôpital de Chicoutimi, Saguenay, QC Canada.
authors.forename: Sandra
authors.initials: S
authors.lastname: Côté
authors.affiliation: Department of Biochemistry, Université de Sherbrooke, Sherbrooke, QC Canada.|ECOGENE-21 Laboratory and Lipid Clinic, CIUSSS du Saguenay-Lac-Saint-Jean - Hôpital de Chicoutimi, Saguenay, QC Canada.
authors.forename: Valérie
authors.initials: V
authors.lastname: Gagné-Ouellet
authors.affiliation: Department of Biochemistry, Université de Sherbrooke, Sherbrooke, QC Canada.|ECOGENE-21 Laboratory and Lipid Clinic, CIUSSS du Saguenay-Lac-Saint-Jean - Hôpital de Chicoutimi, Saguenay, QC Canada.
authors.forename: Simon-Pierre
authors.initials: SP
authors.lastname: Guay
authors.affiliation: Department of Mathematics, Université de Sherbrooke, Sherbrooke, QC Canada.
authors.forename: Catherine
authors.initials: C
authors.lastname: Allard
authors.affiliation: Department of Biochemistry, Université de Sherbrooke, Sherbrooke, QC Canada.|ECOGENE-21 Laboratory and Lipid Clinic, CIUSSS du Saguenay-Lac-Saint-Jean - Hôpital de Chicoutimi, Saguenay, QC Canada.
authors.forename: Andrée-Anne
authors.initials: AA
authors.lastname: Houde
authors.affiliation: ECOGENE-21 Laboratory and Lipid Clinic, CIUSSS du Saguenay-Lac-Saint-Jean - Hôpital de Chicoutimi, Saguenay, QC Canada.|Department of Medicine, Université de Sherbrooke, Sherbrooke, QC Canada.
authors.forename: Patrice
authors.initials: P
authors.lastname: Perron
authors.affiliation: Department of Medicine, Université de Sherbrooke, Sherbrooke, QC Canada.
authors.forename: Jean-Patrice
authors.initials: JP
authors.lastname: Baillargeon
authors.affiliation: ECOGENE-21 Laboratory and Lipid Clinic, CIUSSS du Saguenay-Lac-Saint-Jean - Hôpital de Chicoutimi, Saguenay, QC Canada.|Department of Medicine, Université de Montréal, Montréal, QC Canada.
authors.forename: Daniel
authors.initials: D
authors.lastname: Gaudet
authors.affiliation: Department of Medical Biology, Chicoutimi Hospital, Saguenay, QC Canada.
authors.forename: Renée
authors.initials: R
authors.lastname: Guérin
authors.affiliation: ECOGENE-21 Laboratory and Lipid Clinic, CIUSSS du Saguenay-Lac-Saint-Jean - Hôpital de Chicoutimi, Saguenay, QC Canada.|Department of Medicine, Université de Montréal, Montréal, QC Canada.
authors.forename: Diane
authors.initials: D
authors.lastname: Brisson
authors.affiliation: Department of Medicine, Université de Sherbrooke, Sherbrooke, QC Canada.|Department of Population Medicine, Harvard Pilgrim Health Care Institute, Harvard Medical School, Boston, MA USA.
authors.forename: Marie-France
authors.initials: MF
authors.lastname: Hivert
authors.affiliation: Department of Biochemistry, Université de Sherbrooke, Sherbrooke, QC Canada.|ECOGENE-21 Laboratory and Lipid Clinic, CIUSSS du Saguenay-Lac-Saint-Jean - Hôpital de Chicoutimi, Saguenay, QC Canada.
authors.forename: Luigi
authors.initials: L
authors.lastname: Bouchard
mesh_terms: D000328:Adult; D019175:DNA Methylation; D016640:Diabetes, Gestational / Q000235:genetics*; D044127:Epigenesis, Genetic; D005260:Female; D005312:Fetal Blood / Q000378:metabolism; D005951:Glucose Tolerance Test; D006801:Humans; D007231:Infant, Newborn; D020738:Leptin / Q000378:metabolism*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000235:genetics*; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011264:Pregnancy Trimesters
chemical_list: D020738:Leptin; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
keywords: Brown adipose tissue; Epigenetics; Gestational diabetes mellitus; Hyperglycemia; Pregnancy