PMID- 20188535 OWN - NLM STAT- MEDLINE DCOM- 20110324 LR - 20211203 IS - 1873-4847 (Electronic) IS - 0955-2863 (Print) IS - 0955-2863 (Linking) VI - 22 IP - 1 DP - 2011 Jan TI - Influence of gestational overfeeding on cardiac morphometry and hypertrophic protein markers in fetal sheep. PG - 30-7 LID - 10.1016/j.jnutbio.2009.11.006 [doi] AB - 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-3beta (GSK3beta), 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, GSK3beta and caspase-8 as well as phosphorylated Akt and GSK3beta 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. CI - Copyright (c) 2011 Elsevier Inc. All rights reserved. FAU - Fan, Xiujuan AU - Fan X AD - Center for Cardiovascular Research and Alternative Medicine, University of Wyoming, Laramie, WY 82071, USA. FAU - Turdi, Subat AU - Turdi S FAU - Ford, Stephen P AU - Ford SP FAU - Hua, Yinan AU - Hua Y FAU - Nijland, Mark J AU - Nijland MJ FAU - Zhu, Meijun AU - Zhu M FAU - Nathanielsz, Peter W AU - Nathanielsz PW FAU - Ren, Jun AU - Ren J LA - eng GR - P01 HD021350/HD/NICHD NIH HHS/United States GR - P20 RR016474/RR/NCRR NIH HHS/United States GR - P20 RR016474-09/RR/NCRR NIH HHS/United States GR - P20 RR16474/RR/NCRR NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20100225 PL - United States TA - J Nutr Biochem JT - The Journal of nutritional biochemistry JID - 9010081 RN - 0 (Biomarkers) RN - 0 (Forkhead Transcription Factors) RN - 0 (NFATC Transcription Factors) RN - 0 (Natriuretic Peptides) RN - 0 (RNA, Messenger) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - EC 3.1.3.16 (Calcineurin) SB - IM MH - Animals MH - Biomarkers/metabolism MH - Calcineurin/metabolism MH - Cardiomegaly/*metabolism/*pathology MH - Cardiovascular Diseases/epidemiology MH - Extracellular Space MH - Fascia/pathology MH - Female MH - Fetal Heart/*metabolism/*pathology MH - Forkhead Transcription Factors/metabolism MH - Gene Expression Regulation, Developmental MH - *Maternal Nutritional Physiological Phenomena MH - Myofibrils/pathology MH - NFATC Transcription Factors/metabolism MH - Natriuretic Peptides/genetics/metabolism MH - Overnutrition/*metabolism/*pathology MH - Phosphorylation MH - RNA, Messenger/metabolism MH - Sheep, Domestic MH - TOR Serine-Threonine Kinases/metabolism PMC - PMC2901772 MID - NIHMS184612 EDAT- 2010/03/02 06:00 MHDA- 2011/03/25 06:00 PMCR- 2012/01/01 CRDT- 2010/03/02 06:00 PHST- 2009/08/25 00:00 [received] PHST- 2009/10/29 00:00 [revised] PHST- 2009/11/09 00:00 [accepted] PHST- 2010/03/02 06:00 [entrez] PHST- 2010/03/02 06:00 [pubmed] PHST- 2011/03/25 06:00 [medline] PHST- 2012/01/01 00:00 [pmc-release] AID - S0955-2863(09)00248-4 [pii] AID - 10.1016/j.jnutbio.2009.11.006 [doi] PST - ppublish SO - J Nutr Biochem. 2011 Jan;22(1):30-7. doi: 10.1016/j.jnutbio.2009.11.006. Epub 2010 Feb 25.