{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T13:39:51Z","timestamp":1781012391748,"version":"3.54.1"},"reference-count":45,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2018,2,11]],"date-time":"2018-02-11T00:00:00Z","timestamp":1518307200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001632","name":"Ulster University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001632","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001626","name":"Public Health Agency","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001626","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008302","name":"Department of Education and Learning, Northern Ireland","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008302","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2018,5]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>To demarcate pathological events in the brain as a result of short\u2010term to chronic high\u2010fat\u2010diet (HFD) feeding, which leads to cognitive impairment and neuroinflammation, and to assess the efficacy of Xenin\u201025[Lys(13)PAL] in chronic HFD\u2010fed mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>C57BL\/6 mice were fed an HFD or a normal diet for 18 days, 34 days, 10 and 21 weeks. Cognition was assessed using novel object recognition and the Morris water maze. Markers of insulin signalling and inflammation were measured in brain and plasma using immunohistochemistry, quantitative PCR and multi\u2010array technology. Xenin\u201025[Lys(13)PAL] was also administered for 5 weeks in chronic HFD\u2010fed mice to assess therapeutic potential at a pathological stage.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Recognition memory was consistently impaired in HFD\u2010fed mice and spatial learning was impaired in 18\u2010day and 21\u2010week HFD\u2010fed mice. Gliosis, oxidative stress and IRS\u20101 pSer\n                      <jats:sup>616<\/jats:sup>\n                      were increased in the brain on day 18 in HFD\u2010fed mice and were reduced by Xenin\u201025[Lys(13)PAL] in 21\u2010week HFD\u2010fed mice. In plasma, HFD feeding elevated interleukin (IL)\u20106 and chemokine (C\u2010X\u2010C motif) ligand 1 at day 34 and IL\u20105 at week 10. In the brain, HFD feeding reduced extracellular signal\u2010regulated kinase 2 (ERK2), mechanistic target of rapamycin (mTOR), NF\u2010\u03baB1, protein kinase C (PKC)\u03b8 and Toll\u2010like receptor 4 (TLR4) mRNA at week 10 and increased expression of glucacon\u2010like peptide\u20101 receptor, inhibitor of NF\u2010\u03baB kinase \u03b2, ERK2, mTOR, NF\u2010\u03baB1, PKC\u03b8 and TLR4 at week 21, elevations that were abrogated by Xenin\u201025[Lys(13)PAL].\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>HFD feeding modulates cognitive function, synapse density, inflammation and insulin resistance in the brain. Xenin\u201025[Lys(13)PAL] ameliorated markers of inflammation and insulin signalling dysregulation and may have therapeutic potential in the treatment of diseases associated with neuroinflammation or perturbed insulin signalling in the brain.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.13210","type":"journal-article","created":{"date-parts":[[2018,1,9]],"date-time":"2018-01-09T21:18:30Z","timestamp":1515532710000},"page":"1166-1175","source":"Crossref","is-referenced-by-count":68,"title":["Sustained high\u2010fat diet modulates inflammation, insulin signalling and cognition in mice and a modified xenin peptide ameliorates neuropathology in a chronic high\u2010fat model"],"prefix":"10.1111","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0712-8341","authenticated-orcid":false,"given":"Paul","family":"Denver","sequence":"first","affiliation":[{"name":"Centre for Molecular Biosciences University of Ulster  Coleraine 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