title: Adverse Effect of High-Fat Diet on Metabolic Programming in Offspring Born to a Murine Model of Maternal Hypertension.
abstract: We previously reported that offspring heterozygous mice partially lacking endothelial nitric oxide synthase (eNOS) gene, and born to hypertensive eNOS-/- Knockout mother, are hypertensive. We hypothesized that those offspring when placed on high-fat diet (HFD) will undergo altered metabolic programming increasing their risk for developing metabolic syndrome.
  
  
  
  eNOS-/-KO and wild-type mice (eNOS+/+WT) were cross-bred to produce heterozygous offspring: maternal heterozygous (Mat, eNOS-/+), born from hypertensive eNOS-/-KO mothers; and paternal heterozygous (Pat, eNOS-/+), born from normotensive WT mothers. Mat, eNOS-/+ and Pat, eNOS-/+ female were allocated to HFD or control diet (CD) until 8 weeks of age. Then a metabolic profile was obtained: weight, glucose/insulin tolerance test (GTT, ITT), systolic blood pressure (SBP), serum fasting levels of insulin, adiponectin, leptin, and a lipid panel.
  
  
  
  Weight was not different between all offspring within each diet. GTT curve was higher in Mat, eNOS-/+ vs. Pat, eNOS-/+ offspring on both diet (P < 0.001). In ITT, glucose level at 15 minutes was higher in Mat, eNOS-/+ on HFD. Insulin level was increased in Mat, eNOS-/+ vs. Pat, eNOS-/+ on either diet. SBP was elevated in Mat, eNOS-/+ vs. Pat, eNOS-/+ on CD and was further raised in Mat, eNOS-/+ offspring on HFD (P < 0.001). No other differences were seen except for lower high-density lipoprotein levels in Mat, eNOS-/+ fed HFD (P < 0.003).
  
  
  
  Mat, eNOS-/+ offspring exposed in utero to maternal hypertension and fed HFD postnatally have increased susceptibility for metabolic abnormalities. Thus, maternal HTN is a risk factor for altered fetal metabolic programming.
authors: Division of Maternal Fetal Medicine, Department of Obstetrics, Gynecology and Reproductive Sciences, McGovern Medical School at The University of Texas Health Science Center at Houston, Texas, USA.
authors: Monica
authors: M
authors: Longo
authors: Division of Maternal Fetal Medicine, Department of Obstetrics, Gynecology and Reproductive Sciences, McGovern Medical School at The University of Texas Health Science Center at Houston, Texas, USA.
authors: Jerrie S
authors: JS
authors: Refuerzo
authors: Division of Maternal Fetal Medicine, Department of Obstetrics, Gynecology and Reproductive Sciences, McGovern Medical School at The University of Texas Health Science Center at Houston, Texas, USA.
authors: Lovepreet
authors: L
authors: Mann
authors: Division of Maternal Fetal Medicine, Department of Obstetrics, Gynecology and Reproductive Sciences, McGovern Medical School at The University of Texas Health Science Center at Houston, Texas, USA.
authors: Mateo
authors: M
authors: Leon
authors: Division of Maternal Fetal Medicine, Department of Obstetrics, Gynecology and Reproductive Sciences, McGovern Medical School at The University of Texas Health Science Center at Houston, Texas, USA.
authors: Hind N
authors: HN
authors: Moussa
authors: Division of Maternal Fetal Medicine, Department of Obstetrics, Gynecology and Reproductive Sciences, McGovern Medical School at The University of Texas Health Science Center at Houston, Texas, USA.
authors: Baha M
authors: BM
authors: Sibai
authors: Division of Maternal Fetal Medicine, Department of Obstetrics, Gynecology and Reproductive Sciences, McGovern Medical School at The University of Texas Health Science Center at Houston, Texas, USA.
authors: Sean C
authors: SC
authors: Blackwell
mesh_terms: D052242:Adiponectin / Q000097:blood; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D059305:Diet, High-Fat / Q000009:adverse effects*; D004195:Disease Models, Animal; D005260:Female; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006973:Hypertension / Q000150:complications* / Q000235:genetics / Q000503:physiopathology; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood; D008055:Lipids / Q000097:blood; D024821:Metabolic Syndrome / Q000097:blood / Q000209:etiology* / Q000235:genetics / Q000503:physiopathology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D052250:Nitric Oxide Synthase Type III / Q000172:deficiency / Q000235:genetics; D010641:Phenotype; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012307:Risk Factors; D013997:Time Factors; D015430:Weight Gain
chemical_list: D052242:Adiponectin; C499919:Adipoq protein, mouse; D015415:Biomarkers; D001786:Blood Glucose; D007328:Insulin; D020738:Leptin; D008055:Lipids; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse
keywords: blood pressure; fetal programming; hypertension; maternal hypertension; metabolic syndrome; obesogenic diet; uterine environment.