Adverse effect of high-fat diet on metabolic programming in offspring born to a murine model of maternal hypertension

Monica Longo, Jerrie S. Refuerzo, Lovepreet Mann, Mateo Leon, Hind N. Moussa, Baha M. Sibai, Sean C. Blackwell

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


BACKGROUND 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. METHODS 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. RESULTS 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). CONCLUSIONS 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.

Original languageEnglish (US)
Pages (from-to)1366-1373
Number of pages8
JournalAmerican Journal of Hypertension
Issue number12
StatePublished - 2016


  • Blood pressure
  • Fetal programming
  • Hypertension
  • Maternal hypertension
  • Metabolic syndrome
  • Obesogenic diet
  • Uterine environment

ASJC Scopus subject areas

  • Internal Medicine


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