Influence of gestational overfeeding on myocardial proinflammatory mediators in fetal sheep heart

Machender R. Kandadi, Yinan Hua, Meijun Zhu, Subat Turdi, Peter W. Nathanielsz, Stephen P. Ford, Sreejayan Nair, Jun Ren

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Maternal overnutrition is associated with predisposition of offspring to cardiovascular disease in later life. Since maternal overnutrition may promote fetal and placental inflammatory responses, we hypothesized that maternal overnutrition/obesity increases expression of fetal cardiac proinflammatory mediators and alter cardiac morphometry. Multiparous ewes were fed either 150% of National Research Council (NRC) nutrient recommendations (overfed) or 100% of NRC requirement (control) from 60 days prior to mating to gestation Day 75 (D75), when ewes were euthanized. An additional cohort of overfed and control ewes were necropsied on D135. Cardiac morphometry, histology, mRNA and protein expression of toll-like receptor 4, iNOS, IL-1a, IL-1b, IL-6, IL-18, CD-14, CD-68, M-CSF and protein levels of phosphorylated I-κB and nuclear factor κB (NF-κB) were examined. Immunohistochemistry was performed to assess neutrophil and monocyte infiltration. Crown rump length, left and right ventricular free wall weights as well as left and right ventricular wall thickness were significantly increased in D75 fetuses of overfed mothers. Hematoxylin and eosin staining revealed irregular myofiber orientation and increased interstitial space in fetal ventricular tissues born to overfed mothers. Oil red O staining exhibited marked lipid droplet accumulation in the overfed fetuses. Overfeeding significantly enhanced TLR4, IL-1a, IL-1b IL-6 expression, promoted phosphorylation of IκB, decreased cytoplasmic NF-κB levels and increased neutrophil and monocyte infiltration. Collectively, these data suggest that maternal overfeeding prior to and throughout gestation leads to inflammation in the fetal heart and alters fetal cardiac morphometry.

Original languageEnglish (US)
Pages (from-to)1982-1990
Number of pages9
JournalJournal of Nutritional Biochemistry
Volume24
Issue number11
DOIs
StatePublished - Nov 1 2013

Keywords

  • Fetus
  • Heart
  • Inflammation
  • Maternal overnutrition
  • Morphology

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Nutrition and Dietetics
  • Clinical Biochemistry

Fingerprint Dive into the research topics of 'Influence of gestational overfeeding on myocardial proinflammatory mediators in fetal sheep heart'. Together they form a unique fingerprint.

  • Cite this