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dc.contributor.authorBlackmore, Heather Len
dc.contributor.authorNiu, Youguoen
dc.contributor.authorTwinn, Deniseen
dc.contributor.authorTarry-Adkins, Jane Len
dc.contributor.authorGiussani, Dinoen
dc.contributor.authorOzanne, Susanen
dc.date.accessioned2014-07-18T14:18:50Z
dc.date.available2014-07-18T14:18:50Z
dc.date.issued2014-07-18en
dc.identifier.citationEndocrinology 155, 10. 3970-80. doi: 10.1210/en.2014-1383.
dc.identifier.issn0013-7227
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/245559
dc.description.abstractObese pregnancies are not only associated with adverse consequences for the mother but also the long-term health of her child. Human studies have shown that individuals from obese mothers are at increased risk of premature death from cardiovascular disease (CVD), but are not able to define causality. This study aimed to determine causality using a mouse model of maternal diet-induced obesity. Obesity was induced in female C57BL/6 mice by feeding a diet rich in simple sugars and saturated fat 6 weeks prior to pregnancy and throughout pregnancy and lactation. Control femaleswere fed laboratory chow. Male offspring from both groups were weaned onto chow and studied at 3, 5, 8 and 12 weeks of age for gross cardiac morphometry using stereology, cardiomyocyte cell area by histology and cardiac fetal gene expression using qRT-PCR. Cardiac function was assessed by isolated Langendorff technology at 12 weeks of age and hearts were analysed at the protein level for the expression of the β1 adrenergic receptor, muscarinic type-2 acetylcholine receptor and proteins involved in cardiac contraction. Offspring from obese mothers develop pathologic cardiac hypertrophy associated with re-expression of cardiac fetal genes. By young adulthood these offspring developed severe systolic and diastolic dysfunction and cardiac sympathetic dominance. Importantly, cardiac dysfunction occurred in the absence of any change in corresponding body weight and despite the offspring eating a healthy low fat diet. These findings provide a causal link to explain human observations relating maternal obesity with premature death from CVD in her offspring.
dc.description.sponsorshipHLB, YN and JLTA are funded by the British Heart Foundation. DFT is supported by the MRC Metabolic Diseases Unit. DAG is a Lister Institute Fellow and Royal Society Wolfson Merit Award Holder and is supported by the British Heart Foundation. SEO is a British Heart Foundation Senior Fellow and a member of the MRC Metabolic Diseases Unit.
dc.languageEnglishen
dc.language.isoenen
dc.rightsAttribution 2.0 UK: England & Wales
dc.rightsCreative Commons Attribution License 2.0 UK
dc.rights.urihttp://creativecommons.org/licenses/by/2.0/uk/
dc.subjectcardiac hypertrophyen
dc.subjectprenatal exposure delayed effectsen
dc.subjectmaternal dieten
dc.titleMaternal diet-induced obesity programmes cardiovascular dysfunction in adult male mouse offspring independent of current body weighten
dc.typeArticle
dc.description.versionThis is the final published version. It's also available from the publisher at http://press.endocrine.org/doi/abs/10.1210/en.2014-1383?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub%3Dpubmed&.en
prism.endingPage3980
prism.publicationDate2014en
prism.publicationNameEndocrinologyen
prism.startingPage3970
prism.volume155en
rioxxterms.versionofrecord10.1210/en.2014-1383en
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2014-07-18en
dc.contributor.orcidTwinn, Denise [0000-0003-2610-277X]
dc.contributor.orcidGiussani, Dino [0000-0002-1308-1204]
dc.contributor.orcidOzanne, Susan [0000-0001-8753-5144]
dc.identifier.eissn1945-7170
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idBBSRC (BB/E002668/1)
pubs.funder-project-idBritish Heart Foundation (FS/09/029/27902)
pubs.funder-project-idBritish Heart Foundation (PG/09/037/27387)
pubs.funder-project-idBritish Heart Foundation (PG/13/46/30329)
pubs.funder-project-idBritish Heart Foundation (PG/14/5/30547)
pubs.funder-project-idMRC (MC_UU_12012/4)
pubs.funder-project-idMRC (G0600717B)
pubs.funder-project-idMRC (MC_UU_12012/5)


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Attribution 2.0 UK: England & Wales
Except where otherwise noted, this item's licence is described as Attribution 2.0 UK: England & Wales