Influence of gestational overfeeding on cardiac morphometry and hypertrophic protein markers in fetal sheep.

Abstract

Intrauterine overnutrition is associated with development of cardiovascular disease in adulthood although the underlying mechanism has not been precisely elucidated. This study evaluated the effects of maternal overnutrition on fetal cardiac morphometry and hypertrophy-related mRNA/protein expression. Multiparous ewes were fed either 150% of National Research Council (NRC) nutrient requirements (overfed group) or 100% of NRC requirements (control group) from 60 days before mating to Day 75 (D75) of gestation, when ewes were euthanized. Cardiac morphometry, histology and expression of Akt, forkhead-3a (Foxo3a), glycogen synthase kinase-3β (GSK3β), mammalian target of rapamycin (mTOR), NFATc3 and GATA4, atrial natriuretic factor (ANF), calcineurin A and caspase-8 were examined. Crown rump length, left and right ventricular free wall weights and left ventricular wall thickness were increased in D75 overnourished fetuses. Hematoxylin and eosin staining revealed irregular myofiber orientation and increased interstitial space in heart tissues from overfed group. Masson's trichrome staining displayed myofiber hypertrophy and fascicular disarray in heart tissues from overfed group. Overfeeding significantly enhanced Foxo3a phosphorylation in both ventricles, while protein expression of Akt, Foxo3a, GSK3β and caspase-8 as well as phosphorylated Akt and GSK3β in either ventricle was unaffected. Overfeeding increased left ventricular mTOR, NFATc3 (both total and phosphorylated) and calcineurin A. GATA4, pGATA4 and ANF expression were unchanged in both ventricles. Collectively, our data suggested that overfeeding during early to mid gestation (D75) leads to morphometric changes without overt pathology which may be related to elevated expression of mTOR, NFATc3, calcineurin A and phosphorylation of Foxo3a, mTOR and NFATc3.

• Authors: Xiujuan Fan, Subat Turdi, Stephen P Ford, Yinan Hua, Mark J Nijland, Meijun Zhu, Peter W Nathanielsz, Jun Ren
• Journal: The Journal of nutritional biochemistry (J Nutr Biochem) Vol. 22 Issue 1 Pg. 30-7 (Jan 2011) ISSN: 1873-4847 [Electronic] United States
• PMID: 20188535 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2011 Elsevier Inc. All rights reserved.

Chemical References

• Biomarkers
• Forkhead Transcription Factors
• NFATC Transcription Factors
• Natriuretic Peptides
• RNA, Messenger
• TOR Serine-Threonine Kinases
• Calcineurin

Topics

• Animals
• Biomarkers (metabolism)
• Calcineurin (metabolism)
• Cardiomegaly (metabolism, pathology)
• Cardiovascular Diseases (epidemiology)
• Extracellular Space
• Fascia (pathology)
• Female
• Fetal Heart (metabolism, pathology)
• Forkhead Transcription Factors (metabolism)
• Gene Expression Regulation, Developmental
• Maternal Nutritional Physiological Phenomena
• Myofibrils (pathology)
• NFATC Transcription Factors (metabolism)
• Natriuretic Peptides (genetics, metabolism)
• Overnutrition (metabolism, pathology)
• Phosphorylation
• RNA, Messenger (metabolism)
• Sheep, Domestic
• TOR Serine-Threonine Kinases (metabolism)