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dc.contributor.authorGirousse, Amandineen
dc.contributor.authorVirtue, Samuelen
dc.contributor.authorHart, Danen
dc.contributor.authorVidal-Puig, Antonioen
dc.contributor.authorMurgatroyd, Peter Ren
dc.contributor.authorMouisel, Etienneen
dc.contributor.authorSengenès, Coralieen
dc.contributor.authorSavage, Daviden
dc.date.accessioned2018-09-05T12:40:17Z
dc.date.available2018-09-05T12:40:17Z
dc.date.issued2018-07en
dc.identifier.issn2212-8778
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/279345
dc.description.abstractObjective. Surplus dietary fat cannot be converted into other macronutrient forms or excreted, so has to be stored or oxidized. Healthy mammals store excess energy in the form of triacylgycerol (TAG) in lipid droplets within adipocytes rather than oxidizing it, and thus ultimately gain weight. The ‘overflow hypothesis’ posits that the capacity to increase the size and number of adipocytes is finite and that when this limit is exceeded, fat accumulates in ectopic sites and leads to metabolic disease. Methods. Here we studied the energetic and biochemical consequences of short-term (2-day) excess fat ingestion in a lipodystrophic (A-ZIP/F-1) mouse model, where adipose capacity is severely restricted. Results. In wildtype littermates, this acute exposure to high fat diets resulted in excess energy intake and weight gain without any significant changes in macronutrient oxidation rates, glucose, TAG or insulin levels. In contrast, hyperphagic lipodystrophic mice failed to gain weight; rather they significantly increased hepatic steatosis and fat oxidation. This response was associated with a significant increase in hyperglycaemia, hyperinsulinaemia, glucosuria, hypertriglyceridemia and worsening insulin tolerance. Conclusions. These data suggest that when adipose storage reserves are saturated, excess fat intake necessarily increases fat oxidation and induces oxidative substrate competition which exacerbates insulin resistance resolving any residual energy surplus through excretion of glucose.
dc.format.mediumPrint-Electronicen
dc.languageengen
dc.publisherElsevier
dc.rightsAttribution 4.0 International (CC BY 4.0)
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectLiveren
dc.subjectAdipose Tissueen
dc.subjectAdipocytesen
dc.subjectAnimalsen
dc.subjectMiceen
dc.subjectFatty Liveren
dc.subjectLipodystrophyen
dc.subjectHyperinsulinismen
dc.subjectInsulin Resistanceen
dc.subjectObesityen
dc.subjectWeight Gainen
dc.subjectGlucoseen
dc.subjectLipidsen
dc.subjectDietary Fatsen
dc.subjectEnergy Metabolismen
dc.subjectOxidation-Reductionen
dc.subjectEnergy Intakeen
dc.subjectAdiposityen
dc.subjectDiet, High-Faten
dc.titleSurplus fat rapidly increases fat oxidation and insulin resistance in lipodystrophic mice.en
dc.typeArticle
prism.endingPage29
prism.publicationDate2018en
prism.publicationNameMolecular metabolismen
prism.startingPage24
prism.volume13en
dc.identifier.doi10.17863/CAM.26723
dcterms.dateAccepted2018-05-07en
rioxxterms.versionofrecord10.1016/j.molmet.2018.05.006en
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2018-07en
dc.contributor.orcidGirousse, Amandine [0000-0001-6142-4710]
dc.contributor.orcidVidal-Puig, Antonio [0000-0003-4220-9577]
dc.contributor.orcidMouisel, Etienne [0000-0002-4676-5709]
dc.contributor.orcidSengenès, Coralie [0000-0002-4820-6660]
dc.contributor.orcidSavage, David [0000-0002-7857-7032]
dc.identifier.eissn2212-8778
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idWELLCOME TRUST (107064/Z/15/Z)
pubs.funder-project-idCambridge University Hospitals NHS Foundation Trust (CUH) (146281)
pubs.funder-project-idMRC (G0802051)
pubs.funder-project-idMRC (MC_UU_12012/5)
pubs.funder-project-idMRC (MC_UU_12012/2)
pubs.funder-project-idMRC (G0600717B)
pubs.funder-project-idMRC (MC_G0802535)
pubs.funder-project-idMRC (G0400192)
pubs.funder-project-idMRC (MC_UU_00014/2)
pubs.funder-project-idMRC (MC_UU_00014/5)


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Attribution 4.0 International (CC BY 4.0)
Except where otherwise noted, this item's licence is described as Attribution 4.0 International (CC BY 4.0)