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  • Edlund, Anna K.Stockholms universitet,Institutionen för biokemi och biofysik (author)

Impact of high-fat diet on brain integrity in APOEε3 humanized liver mice

  • BookEnglish

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  • LIBRIS-ID:oai:DiVA.org:su-216611
  • https://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-216611URI

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  • Language:English
  • Summary in:English

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  • Subject category:vet swepub-contenttype
  • Subject category:ovr swepub-publicationtype

Notes

  • Mid-life obesity and dysfunctional brain insulin signaling are associated with an increased risk of dementia. We used FRGN mice (n=11) with humanized APOEε3/ε3 livers to explore the effects of a high-fat-diet (HFD) on markers of insulin signaling, gliosis and synaptic integrityin brain cortical and hippocampal tissues using western blotting and immunohistochemistry.Humanization of the mouse liver produced human-like levels of plasma apolipoprotein B and low-density lipoprotein, which were increased by a 12 week HFD. Mice on the HFD exhibitedincreased phosphorylation of insulin receptor substrate 1 (IRS-1-Ser612) and reduced cortical levels of synaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR). Hippocampal insulin signaling markers were unaffected but the astrocytic marker glial fibrillary acidic protein (GFAP), apolipoprotein E (apoE) and synatophysin were elevated alongsidealtered levels of AMPAR. Our results acquired in a humanized liver mouse model support a key role of the diet in brain health, with implications for diseases like AD. 

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  • Giannisis, AndreasStockholms universitet,Institutionen för biokemi och biofysik(Swepub:su)angi9220 (author)
  • Patra, KalicharanStockholms universitet,Institutionen för biokemi och biofysik (author)
  • Morrema, Tjado H.J. (author)
  • Bial, Greg (author)
  • Foquet, Lander (author)
  • Hoozemans, Jeroen J.M. (author)
  • Nielsen, Henrietta M.Stockholms universitet,Institutionen för biokemi och biofysik (author)
  • Stockholms universitetInstitutionen för biokemi och biofysik (creator_code:org_t)

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