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dc.contributor.authorSanders, Francis WB
dc.contributor.authorAcharjee, Animesh
dc.contributor.authorWalker, Celia
dc.contributor.authorMarney, Luke
dc.contributor.authorRoberts, Lee D
dc.contributor.authorImamura, Fumiaki
dc.contributor.authorJenkins, Benjamin
dc.contributor.authorCase, Jack
dc.contributor.authorRay, Sumantra
dc.contributor.authorVirtue, Samuel
dc.contributor.authorVidal-Puig, Antonio
dc.contributor.authorKuh, Diana
dc.contributor.authorHardy, Rebecca
dc.contributor.authorAllison, Michael
dc.contributor.authorForouhi, Nita
dc.contributor.authorMurray, Andrew
dc.contributor.authorWareham, Nicholas
dc.contributor.authorVacca, Michele
dc.contributor.authorKoulman, Albert
dc.contributor.authorGriffin, Julian
dc.date.accessioned2018-06-21T06:02:52Z
dc.date.available2018-06-21T06:02:52Z
dc.date.issued2018-06-20
dc.identifier.citationGenome Biology. 2018 Jun 20;19(1):79
dc.identifier.issn1474-7596
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/277301
dc.description.abstractBACKGROUND: Diet is a major contributor to metabolic disease risk, but there is controversy as to whether increased incidences of diseases such as non-alcoholic fatty liver disease arise from consumption of saturated fats or free sugars. Here, we investigate whether a sub-set of triacylglycerols (TAGs) were associated with hepatic steatosis and whether they arise from de novo lipogenesis (DNL) from the consumption of carbohydrates. RESULTS: We conduct direct infusion mass spectrometry of lipids in plasma to study the association between specific TAGs and hepatic steatosis assessed by ultrasound and fatty liver index in volunteers from the UK-based Fenland Study and evaluate clustering of TAGs in the National Survey of Health and Development UK cohort. We find that TAGs containing saturated and monounsaturated fatty acids with 16-18 carbons are specifically associated with hepatic steatosis. These TAGs are additionally associated with higher consumption of carbohydrate and saturated fat, hepatic steatosis, and variations in the gene for protein phosphatase 1, regulatory subunit 3b (PPP1R3B), which in part regulates glycogen synthesis. DNL is measured in hyperphagic ob/ob mice, mice on a western diet (high in fat and free sugar) and in healthy humans using stable isotope techniques following high carbohydrate meals, demonstrating the rate of DNL correlates with increased synthesis of this cluster of TAGs. Furthermore, these TAGs are increased in plasma from patients with biopsy-confirmed steatosis. CONCLUSION: A subset of TAGs is associated with hepatic steatosis, even when correcting for common confounding factors. We suggest that hepatic steatosis risk in western populations is in part driven by increased DNL following carbohydrate rich meals in addition to the consumption of saturated fat.
dc.publisherSpringer Science and Business Media LLC
dc.titleHepatic steatosis risk is partly driven by increased de novo lipogenesis following carbohydrate consumption.
dc.typeJournal Article
dc.date.updated2018-06-21T06:02:46Z
dc.language.rfc3066en
dc.rights.holderThe Author(s).
prism.publicationNameGenome Biol
dc.identifier.doi10.17863/CAM.24589
dcterms.dateAccepted2018-05-01
rioxxterms.versionofrecord10.1186/s13059-018-1439-8
dc.contributor.orcidImamura, Fumiaki [0000-0002-6841-8396]
dc.contributor.orcidVidal-Puig, Antonio [0000-0003-4220-9577]
dc.contributor.orcidForouhi, Nita [0000-0002-5041-248X]
dc.contributor.orcidMurray, Andrew [0000-0002-0929-9315]
dc.contributor.orcidWareham, Nicholas [0000-0003-1422-2993]
dc.contributor.orcidVacca, Michele [0000-0002-1973-224X]
dc.contributor.orcidKoulman, Albert [0000-0001-9998-051X]
dc.contributor.orcidGriffin, Julian [0000-0003-1336-7744]
dc.identifier.eissn1474-760X
pubs.funder-project-idMedical Research Council (MR/P01836X/1)
pubs.funder-project-idMedical Research Council (MC_UU_12015/5)
pubs.funder-project-idDepartment of Health (via National Institute for Health Research (NIHR)) (NF-SI-0617-10149)
pubs.funder-project-idDepartment of Health (via National Institute for Health Research (NIHR)) (NF-SI-0512-10135)
pubs.funder-project-idMedical Research Council (MC_UU_12015/1)
pubs.funder-project-idMRC (MC_PC_13046)
pubs.funder-project-idMRC (Unknown)
pubs.funder-project-idMRC (unknown)
pubs.funder-project-idMedical Research Council (G0802051)
pubs.funder-project-idMedical Research Council (MC_UU_12012/5)
pubs.funder-project-idMedical Research Council (MC_UU_12012/2)
pubs.funder-project-idMedical Research Council (MR/P011705/1)
pubs.funder-project-idMedical Research Council (MC_EX_MR/L100002/1)
pubs.funder-project-idMedical Research Council (MC_PC_13030)
pubs.funder-project-idBritish Heart Foundation (None)
pubs.funder-project-idMedical Research Council (G0600717)
pubs.funder-project-idMedical Research Council (MC_G0802535)
pubs.funder-project-idMedical Research Council (G0400192)
pubs.funder-project-idFondazione Umberto Veronesi (unknown)
pubs.funder-project-idMRC (MC_UU_00014/2)
pubs.funder-project-idMRC (MC_UU_00014/5)
cam.issuedOnline2018-06-20


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