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Maternal high fat diet induces early cardiac hypertrophy and alters cardiac metabolism in Sprague Dawley rat offspring
journal contribution
posted on 2018-06-01, 00:00 authored by Kirstie Anne De Jong, Sanna BarrandSanna Barrand, Ryan Wood-BradleyRyan Wood-Bradley, D L de Almeida, J K Czeczor, G D Lopaschuk, James ArmitageJames Armitage, Sean McgeeSean McgeeBACKGROUND AND AIM: Maternal high fat diets (mHFD) have been associated with an increased offspring cardiovascular risk. Recently we found that the class IIa HDAC-MEF2 pathway regulates gene programs controlling fatty acid oxidation in striated muscle. This same pathway controls hypertrophic responses in the heart. We hypothesized that mHFD is associated with activation of signal controlling class II a HDAC activity and activation of genes involved in fatty acid oxidation and cardiac hypertrophy in offspring. METHODS AND RESULTS: Female Sprague Dawley rats were fed either normal fat diet (12%) or high fat diet (43%) three weeks prior to mating, remaining on diets until study completion. Hearts of postnatal day 1 (PN1) and PN10 pups were collected. Bioenergetics and respiration analyses were performed in neonatal ventricular cardiomyocytes (NVCM). In offspring exposed to mHFD, body weight was increased at PN10 accompanied by increased body fat percentage and blood glucose. Heart weight and heart weight to body weight ratio were increased at PN1 and PN10, and were associated with elevated signalling through the AMPK-class IIa HDAC-MEF2 axis. The expression of the MEF2-regulated hypertrophic markers ANP and BNP were increased as were expression of genes involved in fatty acid oxidation. However this was only accompanied by an increased protein expression of fatty acid oxidation enzymes at PN10. NVCM isolated from these pups exhibited increased glycolysis and an impaired substrate flexibility. CONCLUSION: Combined, these results suggest that mHFD induces signalling and transcriptional events indicative of reprogrammed cardiac metabolism and of cardiac hypertrophy in Sprague Dawley rat offspring.
History
Journal
Nutrition, metabolism and cardiovascular diseasesVolume
28Issue
6Pagination
600 - 609Publisher
ElsevierLocation
Amsterdam, The NetherlandsPublisher DOI
ISSN
0939-4753eISSN
1590-3729Language
engPublication classification
C1 Refereed article in a scholarly journalCopyright notice
2018, The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II UniversityUsage metrics
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Maternal high fat dietCardiovascular riskCardiac hypertrophyCardiac metabolismScience & TechnologyLife Sciences & BiomedicineCardiac & Cardiovascular SystemsEndocrinology & MetabolismNutrition & DieteticsCardiovascular System & CardiologyMYOCARDIAL SUBSTRATE METABOLISMENERGY-METABOLISMNUCLEAR EXPORTPREGNANCYDYSFUNCTIONOBESITYAMPKTRANSCRIPTIONACTIVATIONRESISTANCE
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